Screening High-Risk Women Veterans for Breast Cancer

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The number of women seeking care from the Veterans Health Administration (VHA) is increasing.1 In 2015, there were 2 million women veterans in the United States, which is 9.4% of the total veteran population. This group is expected to increase at an average of about 18,000 women per year for the next 10 years.2 The percentage of women veterans who are US Department of Veterans Affairs (VA) users aged 45 to 64 years rose 46% from 2000 to 2015.1,3-4 It is estimated that 15% of veterans who used VA services in 2020 were women.1 Nineteen percent of women veterans are Black.1 The median age of women veterans in 2015 was 50 years.5 Breast cancer is the leading cancer affecting female veterans, and data suggest they have an increased risk of breast cancer based on unique service-related exposures.1,6-9

In the US, about 10 million women are eligible for breast cancer preventive therapy, including, but not limited to, medications, surgery, or lifestyle changes.10 Secondary prevention options include change in surveillance that can reduce their risk or identify cancer at an earlier stage when treatment is more effective. The United States Preventive Services Task Force, the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the National Institute for Health and Care Excellence, and the Oncology Nursing Society recommend screening women aged ≥ 35 years to assess breast cancer risk.11-18 If a woman is at increased risk, she may be a candidate for chemoprevention, prozphylactic surgery, and possibly an enhanced screening regimen.

Urban and minority women are an understudied population. Most veterans (75%) live in urban or suburban settings.19,20 Urban veteran women constitute an important potential study population.

Chemoprevention measures have been underused because of factors involving both women and their health care providers. A large proportion of women are unaware of their higher risk status due to lack of adequate screening and risk assessment.21,22 In addition to patient lack of awareness of their high-risk status, primary care physicians are also reluctant to prescribe chemopreventive agents due to a lack of comfort or familiarity with the risks and benefits.23-26 The STAR2015, BCPT2005, IBIS2014, MAP3 2011, IBIS-I 2014, and IBIS II 2014 studies clearly demonstrate a 49 to 62% reduction in risk for women using chemoprevention such as selective estrogen receptor modulators or aromatase inhibitors, respectively.27-32 Yet only 4 to 9% of high-risk women not enrolled in a clinical trial are using chemoprevention.33-39

The possibility of developing breast cancer also may be increased because of a positive family history or being a member of a family in which there is a known susceptibility gene mutation.40 Based on these risk factors, women may be eligible for tailored follow-up and genetic counseling.41-44

Nationally, 7 to 10% of the civilian US population will experience posttraumatic stress disorder (PTSD).45 The rates are remarkably higher for women veterans, with roughly 20% diagnosed with PTSD.46,47 Anxiety and PTSD have been implicated in poor adherence to medical advice.48,49

In 2014, a national VA multidisciplinary group focused on breast cancer prevention, detection, treatment, and research to address breast health in the growing population of women veterans. High-risk breast cancer screenings are not routinely carried out by the VA in primary care, women’s health, or oncology services. Furthermore, the recording of screening questionnaire results was not synchronized until a standard questionnaire was created and approved as a template by this group in the VA electronic medical record (EMR) in 2015.

Several prediction models can identify which women are at an increased risk of developing breast cancer. The most commonly used risk assessment model, the Gail breast cancer risk assessment tool (BCRAT), has been refined to include women of additional ethnicities (https://www.cancer.gov/bcrisktool).

This pilot project was launched to identify an effective manner to screen women veterans regarding their risk of developing breast cancer and refer them for chemoprevention education or genetic counseling as appropriate.

 

 

Methods

A high-risk breast cancer screening questionnaire based on the Gail BCRAT and including lifestyle questions was developed and included as a note template in the VA EMR. The James J. Peters VA Medical Center, Bronx, NY (JJPVAMC) and the Washington DC VA Medical Center (DCVAMC) ran a pilot study between 2015 and 2018 using this breast cancer screening questionnaire to collect data from women veterans. Quality Executive Committee and institutional review board approvals were granted respectively.

Eligibility criteria included women aged ≥ 35 years with no personal history of breast cancer. Most patients were self-referred, but participants also were recruited during VA Breast Cancer Awareness month events, health fairs, or at informational tables in the hospital lobbies. After completing the 20 multiple choice questionnaire with a study team member, either in person or over the phone, a 5-year and lifetime risk of invasive breast cancer was calculated using the Gail BCRAT. A woman is considered high risk and eligible for chemoprevention if her 5-year risk is > 1.66% or her lifetime risk is ≥ 20%. Eligibility for genetic counseling is based on the Breast Cancer Referral Screening Tool, which includes a personal or family history of breast or ovarian cancer and Jewish ancestry.

All patients were notified of their average or high risk status by a clinician. Those who were deemed to be average risk received a follow-up letter in the mail with instructions (eg, to follow-up with a yearly mammogram). Those who were deemed to be high risk for developing breast cancer were asked to come in for an appointment with the study principal investigator (a VA oncologist/breast cancer specialist) to discuss prevention options, further screening, or referrals to genetic counseling. Depending on a patient’s other health factors, a woman at high risk for developing breast cancer also may be a candidate for chemoprevention with tamoxifen, raloxifene, exemestane, anastrozole, or letrozole.

Data on the participant’s lifestyle, including exercise, diet, and smoking, were evaluated to determine whether these factors had an impact on risk status.

Results

The JJP and DC VAMCs screened 103 women veterans between 2015 and 2018. Four patients were excluded for nonveteran (spousal) status, leaving 99 women veterans with a mean age of 54 years. The most common self-reported races were Black (60%), non-Hispanic White (14%), and Hispanic or Latino (13%) (Table 1).

Women veterans in our study were nearly 3-times more likely than the general population were to receive a high-risk Gail Score/BCRAT (35% vs 13%, respectively).50,51 Of this subset, 46% had breast biopsies, and 86% had a positive family history. Thirty-one percent of Black women in our study were high risk, while nationally, 8.2 to 13.3% of Black women aged 50 to 59 years are considered high risk.50,51 Of the Black high-risk group with a high Gail/BCRAT score, 94% had a positive family history, and 33% had a history of breast biopsy (Table 2).

Of the 35 high-risk patients 26 (74%) patients accepted consultations for chemoprevention and 5 (19%) started chemoprevention. Of this high-risk group, 13 (37%) patients were referred for genetic counseling (Table 3).44 The prevalence of PTSD was present in 31% of high-risk women and 29% of the cohort (Figure).The lifestyle questions indicated that, among all participants, 79% had an overweight or obese body mass index; 58% exercised weekly; 51% consumed alcohol; 14% were smokers; and 21% consumed 3 to 4 servings of fruits/vegetables daily.

 

 

Discussion

Breast cancer is the most common cancer in women.52 The number of women with breast cancer in the VHA has more than tripled from 1995 to 2012.1 The lifetime risk of developing breast cancer in the general population is about 13%.50 This rate can be affected by risk factors including age, hormone exposure, family history, radiation exposure, and lifestyle factors, such as weight and alcohol use.6,52-56 In the United States, invasive breast cancer affects 1 in 8 women.50,52,57

Our screened population showed nearly 3 times as many women veterans were at an increased risk for breast cancer when compared with historical averages in US women. This difference may be based on a high rate of prior breast biopsies or positive family history, although a provocative study using the Surveillance, Epidemiology, and End Results database showed military women to have higher rates of breast cancer as well.9 Historically, Blacks are vastly understudied in clinical research with only 5% representation on a national level.5,58 The urban locations of both pilot sites (Washington, DC and Bronx, NY) allowed for the inclusion of minority patients in our study. We found that the rates of breast cancer in Black women veterans to be higher than seen nationally, possibly prompting further screening initiatives for this understudied population.

Our pilot study’s chemoprevention utilization (19%) was double the < 10% seen in the national population.33-35 The presence of a knowledgeable breast health practitioner to recruit study participants and offer personalized counseling to women veterans is a likely factor in overcoming barriers to chemopreventive acceptance. These participants may have been motivated to seek care for their high-risk status given a strong family history and prior breast biopsies.

Interestingly, a 3-fold higher PTSD rate was seen in this pilot population (29%) when compared with PTSD rates in the general female population (7-10%) and still one-third higher than the general population of women veterans (20%).45-47 Mental health, anxiety, and PTSD have been barriers to patients who sought treatment and have been implicated in poor adherence to medical advice.48,49 Cancer screening can induce anxiety in patients, and it may be amplified in patients with PTSD. It was remarkable that although adherence with screening recommendations is decreased when PTSD is present, our patient population demonstrated a higher rate of screening adherence.

Women who are seen at the VA often use multiple clinical specialties, and their EMR can be accessed across VA medical centers nationwide. Therefore, identifying women veterans who meet screening criteria is easily attainable within the VA.

When comparing high-risk with average risk women, the lifestyle results (BMI, smoking history, exercise and consumption of fruits, vegetables and alcohol) were essentially the same. Lifestyle factors were similar to national population rates and were unlikely to impact risk levels.

Limitations

Study limitations included a high number of self-referrals and the large percentage of patients with a family history of breast cancer, making them more likely to seek screening. The higher-than-average risk of breast cancer may be driven by a high rate of breast biopsies and a strong family history. Lifestyle metrics could not be accurately compared to other national assessments of lifestyle factors due to the difference in data points that we used or the format of our questions.

 

 

Conclusions

As the number of women veterans increases and the incidence of breast cancer in women veterans rise, chemoprevention options should follow national guidelines. To our knowledge, this is the only oncology study with 60% Black women veterans. This study had a higher participation rate for Black women veterans than is typically seen in national research studies and shows the VA to be a germane source for further understanding of an understudied population that may benefit from increased screening for breast cancer.

A team-based, multidisciplinary model that meets the unique healthcare needs of women veterans results in a patient-centric delivery of care for assessing breast cancer risk status and prevention options. This model can be replicated nationally by directing primary care physicians and women’s health practitioners to a risk-assessment questionnaire and referring high-risk women for appropriate preventative care. Given that these results show chemoprevention adherence rates doubled those seen nationally, perhaps techniques used within this VA pilot study may be adapted to decrease breast cancer incidence nationally.

Since the rate of PTSD among women veterans is triple the national average, we would expect adherence rates to be lower in our patient cohort. However, the multidisciplinary approach we used in this study (eg, 1:1 consultation with oncologist; genetic counseling referrals; mental health support available), may have improved adherence rates. Perhaps the high rates of PTSD seen in the VA patient population can be a useful way to explore patient adherence rates in those with mental illness and medical conditions.

Future research with a larger cohort may lead to greater insight into the correlation between PTSD and adherence to treatment. Exploring the connection between breast cancer, epigenetics, and specific military service-related exposures could be an area of analysis among this veteran population exhibiting increased breast cancer rates. VAMCs are situated in rural, suburban, and urban locations across the United States and offers a diverse socioeconomic and ethnic patient population for inclusion in clinical investigations. Women veterans make up a small subpopulation of women in the United States, but it is worth considering VA patients as an untapped resource for research collaboration.

Acknowledgements

The authors thank Steven Sanchez and Marissa Vallette, PhD, Breast Health Research Group. This research project was approved by the James J. Peters VA Medical Center Quality Executive Committee and the Washington, DC VA Medical Center Institutional Review Board. This work was supported by the US Department of Veterans Affairs. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author disclosures

The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

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Yeun-Hee Anna Park is Chief of Hematology/Oncology; Alison Keller is a Research Coordinator; and Ta-Chueh Melody Hsu is a Research Nurse Practitioner, all at James J. Peters Veterans Affairs Medical Center, Bronx, New York. Balmatee Bidassie is an Industrial Engineer VA Center for Applied Systems Engineering (VA-CASE), VISN11 - Veterans Engineering Resource Center (VERC) at Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana. Vickie Venne was a Senior Genetic Counselor for the US Department of Veterans Affairs (VA) Genomic Medicine Services, and Sarah Colonna is a Hematologist/Oncologist; both at George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah. Douglas Hawley is a Hematologist/Oncologist at Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio. Lori Hoffman-Högg is a ONS Clinical Nurse Advisor for the Oncology Field Advisory Committee and VHA National Program Manager for Prevention Policy at Veterans Health Administration (VHA) National Center for Health Promotion and Disease Prevention, Durham, North Carolina and VHA Office of Nursing Services, Washington, DC. Bernadette Heron is a Program Manager at Veterans Health Administration, Pharmacy Benefits Management Services in Hines, Illinois. Anita Aggarwal is a Hematologist/Oncologist Washington Veterans Affairs Medical Center, Washington, DC.

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Yeun-Hee Anna Park is Chief of Hematology/Oncology; Alison Keller is a Research Coordinator; and Ta-Chueh Melody Hsu is a Research Nurse Practitioner, all at James J. Peters Veterans Affairs Medical Center, Bronx, New York. Balmatee Bidassie is an Industrial Engineer VA Center for Applied Systems Engineering (VA-CASE), VISN11 - Veterans Engineering Resource Center (VERC) at Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana. Vickie Venne was a Senior Genetic Counselor for the US Department of Veterans Affairs (VA) Genomic Medicine Services, and Sarah Colonna is a Hematologist/Oncologist; both at George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah. Douglas Hawley is a Hematologist/Oncologist at Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio. Lori Hoffman-Högg is a ONS Clinical Nurse Advisor for the Oncology Field Advisory Committee and VHA National Program Manager for Prevention Policy at Veterans Health Administration (VHA) National Center for Health Promotion and Disease Prevention, Durham, North Carolina and VHA Office of Nursing Services, Washington, DC. Bernadette Heron is a Program Manager at Veterans Health Administration, Pharmacy Benefits Management Services in Hines, Illinois. Anita Aggarwal is a Hematologist/Oncologist Washington Veterans Affairs Medical Center, Washington, DC.

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Yeun-Hee Anna Park is Chief of Hematology/Oncology; Alison Keller is a Research Coordinator; and Ta-Chueh Melody Hsu is a Research Nurse Practitioner, all at James J. Peters Veterans Affairs Medical Center, Bronx, New York. Balmatee Bidassie is an Industrial Engineer VA Center for Applied Systems Engineering (VA-CASE), VISN11 - Veterans Engineering Resource Center (VERC) at Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana. Vickie Venne was a Senior Genetic Counselor for the US Department of Veterans Affairs (VA) Genomic Medicine Services, and Sarah Colonna is a Hematologist/Oncologist; both at George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah. Douglas Hawley is a Hematologist/Oncologist at Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio. Lori Hoffman-Högg is a ONS Clinical Nurse Advisor for the Oncology Field Advisory Committee and VHA National Program Manager for Prevention Policy at Veterans Health Administration (VHA) National Center for Health Promotion and Disease Prevention, Durham, North Carolina and VHA Office of Nursing Services, Washington, DC. Bernadette Heron is a Program Manager at Veterans Health Administration, Pharmacy Benefits Management Services in Hines, Illinois. Anita Aggarwal is a Hematologist/Oncologist Washington Veterans Affairs Medical Center, Washington, DC.

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The number of women seeking care from the Veterans Health Administration (VHA) is increasing.1 In 2015, there were 2 million women veterans in the United States, which is 9.4% of the total veteran population. This group is expected to increase at an average of about 18,000 women per year for the next 10 years.2 The percentage of women veterans who are US Department of Veterans Affairs (VA) users aged 45 to 64 years rose 46% from 2000 to 2015.1,3-4 It is estimated that 15% of veterans who used VA services in 2020 were women.1 Nineteen percent of women veterans are Black.1 The median age of women veterans in 2015 was 50 years.5 Breast cancer is the leading cancer affecting female veterans, and data suggest they have an increased risk of breast cancer based on unique service-related exposures.1,6-9

In the US, about 10 million women are eligible for breast cancer preventive therapy, including, but not limited to, medications, surgery, or lifestyle changes.10 Secondary prevention options include change in surveillance that can reduce their risk or identify cancer at an earlier stage when treatment is more effective. The United States Preventive Services Task Force, the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the National Institute for Health and Care Excellence, and the Oncology Nursing Society recommend screening women aged ≥ 35 years to assess breast cancer risk.11-18 If a woman is at increased risk, she may be a candidate for chemoprevention, prozphylactic surgery, and possibly an enhanced screening regimen.

Urban and minority women are an understudied population. Most veterans (75%) live in urban or suburban settings.19,20 Urban veteran women constitute an important potential study population.

Chemoprevention measures have been underused because of factors involving both women and their health care providers. A large proportion of women are unaware of their higher risk status due to lack of adequate screening and risk assessment.21,22 In addition to patient lack of awareness of their high-risk status, primary care physicians are also reluctant to prescribe chemopreventive agents due to a lack of comfort or familiarity with the risks and benefits.23-26 The STAR2015, BCPT2005, IBIS2014, MAP3 2011, IBIS-I 2014, and IBIS II 2014 studies clearly demonstrate a 49 to 62% reduction in risk for women using chemoprevention such as selective estrogen receptor modulators or aromatase inhibitors, respectively.27-32 Yet only 4 to 9% of high-risk women not enrolled in a clinical trial are using chemoprevention.33-39

The possibility of developing breast cancer also may be increased because of a positive family history or being a member of a family in which there is a known susceptibility gene mutation.40 Based on these risk factors, women may be eligible for tailored follow-up and genetic counseling.41-44

Nationally, 7 to 10% of the civilian US population will experience posttraumatic stress disorder (PTSD).45 The rates are remarkably higher for women veterans, with roughly 20% diagnosed with PTSD.46,47 Anxiety and PTSD have been implicated in poor adherence to medical advice.48,49

In 2014, a national VA multidisciplinary group focused on breast cancer prevention, detection, treatment, and research to address breast health in the growing population of women veterans. High-risk breast cancer screenings are not routinely carried out by the VA in primary care, women’s health, or oncology services. Furthermore, the recording of screening questionnaire results was not synchronized until a standard questionnaire was created and approved as a template by this group in the VA electronic medical record (EMR) in 2015.

Several prediction models can identify which women are at an increased risk of developing breast cancer. The most commonly used risk assessment model, the Gail breast cancer risk assessment tool (BCRAT), has been refined to include women of additional ethnicities (https://www.cancer.gov/bcrisktool).

This pilot project was launched to identify an effective manner to screen women veterans regarding their risk of developing breast cancer and refer them for chemoprevention education or genetic counseling as appropriate.

 

 

Methods

A high-risk breast cancer screening questionnaire based on the Gail BCRAT and including lifestyle questions was developed and included as a note template in the VA EMR. The James J. Peters VA Medical Center, Bronx, NY (JJPVAMC) and the Washington DC VA Medical Center (DCVAMC) ran a pilot study between 2015 and 2018 using this breast cancer screening questionnaire to collect data from women veterans. Quality Executive Committee and institutional review board approvals were granted respectively.

Eligibility criteria included women aged ≥ 35 years with no personal history of breast cancer. Most patients were self-referred, but participants also were recruited during VA Breast Cancer Awareness month events, health fairs, or at informational tables in the hospital lobbies. After completing the 20 multiple choice questionnaire with a study team member, either in person or over the phone, a 5-year and lifetime risk of invasive breast cancer was calculated using the Gail BCRAT. A woman is considered high risk and eligible for chemoprevention if her 5-year risk is > 1.66% or her lifetime risk is ≥ 20%. Eligibility for genetic counseling is based on the Breast Cancer Referral Screening Tool, which includes a personal or family history of breast or ovarian cancer and Jewish ancestry.

All patients were notified of their average or high risk status by a clinician. Those who were deemed to be average risk received a follow-up letter in the mail with instructions (eg, to follow-up with a yearly mammogram). Those who were deemed to be high risk for developing breast cancer were asked to come in for an appointment with the study principal investigator (a VA oncologist/breast cancer specialist) to discuss prevention options, further screening, or referrals to genetic counseling. Depending on a patient’s other health factors, a woman at high risk for developing breast cancer also may be a candidate for chemoprevention with tamoxifen, raloxifene, exemestane, anastrozole, or letrozole.

Data on the participant’s lifestyle, including exercise, diet, and smoking, were evaluated to determine whether these factors had an impact on risk status.

Results

The JJP and DC VAMCs screened 103 women veterans between 2015 and 2018. Four patients were excluded for nonveteran (spousal) status, leaving 99 women veterans with a mean age of 54 years. The most common self-reported races were Black (60%), non-Hispanic White (14%), and Hispanic or Latino (13%) (Table 1).

Women veterans in our study were nearly 3-times more likely than the general population were to receive a high-risk Gail Score/BCRAT (35% vs 13%, respectively).50,51 Of this subset, 46% had breast biopsies, and 86% had a positive family history. Thirty-one percent of Black women in our study were high risk, while nationally, 8.2 to 13.3% of Black women aged 50 to 59 years are considered high risk.50,51 Of the Black high-risk group with a high Gail/BCRAT score, 94% had a positive family history, and 33% had a history of breast biopsy (Table 2).

Of the 35 high-risk patients 26 (74%) patients accepted consultations for chemoprevention and 5 (19%) started chemoprevention. Of this high-risk group, 13 (37%) patients were referred for genetic counseling (Table 3).44 The prevalence of PTSD was present in 31% of high-risk women and 29% of the cohort (Figure).The lifestyle questions indicated that, among all participants, 79% had an overweight or obese body mass index; 58% exercised weekly; 51% consumed alcohol; 14% were smokers; and 21% consumed 3 to 4 servings of fruits/vegetables daily.

 

 

Discussion

Breast cancer is the most common cancer in women.52 The number of women with breast cancer in the VHA has more than tripled from 1995 to 2012.1 The lifetime risk of developing breast cancer in the general population is about 13%.50 This rate can be affected by risk factors including age, hormone exposure, family history, radiation exposure, and lifestyle factors, such as weight and alcohol use.6,52-56 In the United States, invasive breast cancer affects 1 in 8 women.50,52,57

Our screened population showed nearly 3 times as many women veterans were at an increased risk for breast cancer when compared with historical averages in US women. This difference may be based on a high rate of prior breast biopsies or positive family history, although a provocative study using the Surveillance, Epidemiology, and End Results database showed military women to have higher rates of breast cancer as well.9 Historically, Blacks are vastly understudied in clinical research with only 5% representation on a national level.5,58 The urban locations of both pilot sites (Washington, DC and Bronx, NY) allowed for the inclusion of minority patients in our study. We found that the rates of breast cancer in Black women veterans to be higher than seen nationally, possibly prompting further screening initiatives for this understudied population.

Our pilot study’s chemoprevention utilization (19%) was double the < 10% seen in the national population.33-35 The presence of a knowledgeable breast health practitioner to recruit study participants and offer personalized counseling to women veterans is a likely factor in overcoming barriers to chemopreventive acceptance. These participants may have been motivated to seek care for their high-risk status given a strong family history and prior breast biopsies.

Interestingly, a 3-fold higher PTSD rate was seen in this pilot population (29%) when compared with PTSD rates in the general female population (7-10%) and still one-third higher than the general population of women veterans (20%).45-47 Mental health, anxiety, and PTSD have been barriers to patients who sought treatment and have been implicated in poor adherence to medical advice.48,49 Cancer screening can induce anxiety in patients, and it may be amplified in patients with PTSD. It was remarkable that although adherence with screening recommendations is decreased when PTSD is present, our patient population demonstrated a higher rate of screening adherence.

Women who are seen at the VA often use multiple clinical specialties, and their EMR can be accessed across VA medical centers nationwide. Therefore, identifying women veterans who meet screening criteria is easily attainable within the VA.

When comparing high-risk with average risk women, the lifestyle results (BMI, smoking history, exercise and consumption of fruits, vegetables and alcohol) were essentially the same. Lifestyle factors were similar to national population rates and were unlikely to impact risk levels.

Limitations

Study limitations included a high number of self-referrals and the large percentage of patients with a family history of breast cancer, making them more likely to seek screening. The higher-than-average risk of breast cancer may be driven by a high rate of breast biopsies and a strong family history. Lifestyle metrics could not be accurately compared to other national assessments of lifestyle factors due to the difference in data points that we used or the format of our questions.

 

 

Conclusions

As the number of women veterans increases and the incidence of breast cancer in women veterans rise, chemoprevention options should follow national guidelines. To our knowledge, this is the only oncology study with 60% Black women veterans. This study had a higher participation rate for Black women veterans than is typically seen in national research studies and shows the VA to be a germane source for further understanding of an understudied population that may benefit from increased screening for breast cancer.

A team-based, multidisciplinary model that meets the unique healthcare needs of women veterans results in a patient-centric delivery of care for assessing breast cancer risk status and prevention options. This model can be replicated nationally by directing primary care physicians and women’s health practitioners to a risk-assessment questionnaire and referring high-risk women for appropriate preventative care. Given that these results show chemoprevention adherence rates doubled those seen nationally, perhaps techniques used within this VA pilot study may be adapted to decrease breast cancer incidence nationally.

Since the rate of PTSD among women veterans is triple the national average, we would expect adherence rates to be lower in our patient cohort. However, the multidisciplinary approach we used in this study (eg, 1:1 consultation with oncologist; genetic counseling referrals; mental health support available), may have improved adherence rates. Perhaps the high rates of PTSD seen in the VA patient population can be a useful way to explore patient adherence rates in those with mental illness and medical conditions.

Future research with a larger cohort may lead to greater insight into the correlation between PTSD and adherence to treatment. Exploring the connection between breast cancer, epigenetics, and specific military service-related exposures could be an area of analysis among this veteran population exhibiting increased breast cancer rates. VAMCs are situated in rural, suburban, and urban locations across the United States and offers a diverse socioeconomic and ethnic patient population for inclusion in clinical investigations. Women veterans make up a small subpopulation of women in the United States, but it is worth considering VA patients as an untapped resource for research collaboration.

Acknowledgements

The authors thank Steven Sanchez and Marissa Vallette, PhD, Breast Health Research Group. This research project was approved by the James J. Peters VA Medical Center Quality Executive Committee and the Washington, DC VA Medical Center Institutional Review Board. This work was supported by the US Department of Veterans Affairs. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author disclosures

The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

The number of women seeking care from the Veterans Health Administration (VHA) is increasing.1 In 2015, there were 2 million women veterans in the United States, which is 9.4% of the total veteran population. This group is expected to increase at an average of about 18,000 women per year for the next 10 years.2 The percentage of women veterans who are US Department of Veterans Affairs (VA) users aged 45 to 64 years rose 46% from 2000 to 2015.1,3-4 It is estimated that 15% of veterans who used VA services in 2020 were women.1 Nineteen percent of women veterans are Black.1 The median age of women veterans in 2015 was 50 years.5 Breast cancer is the leading cancer affecting female veterans, and data suggest they have an increased risk of breast cancer based on unique service-related exposures.1,6-9

In the US, about 10 million women are eligible for breast cancer preventive therapy, including, but not limited to, medications, surgery, or lifestyle changes.10 Secondary prevention options include change in surveillance that can reduce their risk or identify cancer at an earlier stage when treatment is more effective. The United States Preventive Services Task Force, the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the National Institute for Health and Care Excellence, and the Oncology Nursing Society recommend screening women aged ≥ 35 years to assess breast cancer risk.11-18 If a woman is at increased risk, she may be a candidate for chemoprevention, prozphylactic surgery, and possibly an enhanced screening regimen.

Urban and minority women are an understudied population. Most veterans (75%) live in urban or suburban settings.19,20 Urban veteran women constitute an important potential study population.

Chemoprevention measures have been underused because of factors involving both women and their health care providers. A large proportion of women are unaware of their higher risk status due to lack of adequate screening and risk assessment.21,22 In addition to patient lack of awareness of their high-risk status, primary care physicians are also reluctant to prescribe chemopreventive agents due to a lack of comfort or familiarity with the risks and benefits.23-26 The STAR2015, BCPT2005, IBIS2014, MAP3 2011, IBIS-I 2014, and IBIS II 2014 studies clearly demonstrate a 49 to 62% reduction in risk for women using chemoprevention such as selective estrogen receptor modulators or aromatase inhibitors, respectively.27-32 Yet only 4 to 9% of high-risk women not enrolled in a clinical trial are using chemoprevention.33-39

The possibility of developing breast cancer also may be increased because of a positive family history or being a member of a family in which there is a known susceptibility gene mutation.40 Based on these risk factors, women may be eligible for tailored follow-up and genetic counseling.41-44

Nationally, 7 to 10% of the civilian US population will experience posttraumatic stress disorder (PTSD).45 The rates are remarkably higher for women veterans, with roughly 20% diagnosed with PTSD.46,47 Anxiety and PTSD have been implicated in poor adherence to medical advice.48,49

In 2014, a national VA multidisciplinary group focused on breast cancer prevention, detection, treatment, and research to address breast health in the growing population of women veterans. High-risk breast cancer screenings are not routinely carried out by the VA in primary care, women’s health, or oncology services. Furthermore, the recording of screening questionnaire results was not synchronized until a standard questionnaire was created and approved as a template by this group in the VA electronic medical record (EMR) in 2015.

Several prediction models can identify which women are at an increased risk of developing breast cancer. The most commonly used risk assessment model, the Gail breast cancer risk assessment tool (BCRAT), has been refined to include women of additional ethnicities (https://www.cancer.gov/bcrisktool).

This pilot project was launched to identify an effective manner to screen women veterans regarding their risk of developing breast cancer and refer them for chemoprevention education or genetic counseling as appropriate.

 

 

Methods

A high-risk breast cancer screening questionnaire based on the Gail BCRAT and including lifestyle questions was developed and included as a note template in the VA EMR. The James J. Peters VA Medical Center, Bronx, NY (JJPVAMC) and the Washington DC VA Medical Center (DCVAMC) ran a pilot study between 2015 and 2018 using this breast cancer screening questionnaire to collect data from women veterans. Quality Executive Committee and institutional review board approvals were granted respectively.

Eligibility criteria included women aged ≥ 35 years with no personal history of breast cancer. Most patients were self-referred, but participants also were recruited during VA Breast Cancer Awareness month events, health fairs, or at informational tables in the hospital lobbies. After completing the 20 multiple choice questionnaire with a study team member, either in person or over the phone, a 5-year and lifetime risk of invasive breast cancer was calculated using the Gail BCRAT. A woman is considered high risk and eligible for chemoprevention if her 5-year risk is > 1.66% or her lifetime risk is ≥ 20%. Eligibility for genetic counseling is based on the Breast Cancer Referral Screening Tool, which includes a personal or family history of breast or ovarian cancer and Jewish ancestry.

All patients were notified of their average or high risk status by a clinician. Those who were deemed to be average risk received a follow-up letter in the mail with instructions (eg, to follow-up with a yearly mammogram). Those who were deemed to be high risk for developing breast cancer were asked to come in for an appointment with the study principal investigator (a VA oncologist/breast cancer specialist) to discuss prevention options, further screening, or referrals to genetic counseling. Depending on a patient’s other health factors, a woman at high risk for developing breast cancer also may be a candidate for chemoprevention with tamoxifen, raloxifene, exemestane, anastrozole, or letrozole.

Data on the participant’s lifestyle, including exercise, diet, and smoking, were evaluated to determine whether these factors had an impact on risk status.

Results

The JJP and DC VAMCs screened 103 women veterans between 2015 and 2018. Four patients were excluded for nonveteran (spousal) status, leaving 99 women veterans with a mean age of 54 years. The most common self-reported races were Black (60%), non-Hispanic White (14%), and Hispanic or Latino (13%) (Table 1).

Women veterans in our study were nearly 3-times more likely than the general population were to receive a high-risk Gail Score/BCRAT (35% vs 13%, respectively).50,51 Of this subset, 46% had breast biopsies, and 86% had a positive family history. Thirty-one percent of Black women in our study were high risk, while nationally, 8.2 to 13.3% of Black women aged 50 to 59 years are considered high risk.50,51 Of the Black high-risk group with a high Gail/BCRAT score, 94% had a positive family history, and 33% had a history of breast biopsy (Table 2).

Of the 35 high-risk patients 26 (74%) patients accepted consultations for chemoprevention and 5 (19%) started chemoprevention. Of this high-risk group, 13 (37%) patients were referred for genetic counseling (Table 3).44 The prevalence of PTSD was present in 31% of high-risk women and 29% of the cohort (Figure).The lifestyle questions indicated that, among all participants, 79% had an overweight or obese body mass index; 58% exercised weekly; 51% consumed alcohol; 14% were smokers; and 21% consumed 3 to 4 servings of fruits/vegetables daily.

 

 

Discussion

Breast cancer is the most common cancer in women.52 The number of women with breast cancer in the VHA has more than tripled from 1995 to 2012.1 The lifetime risk of developing breast cancer in the general population is about 13%.50 This rate can be affected by risk factors including age, hormone exposure, family history, radiation exposure, and lifestyle factors, such as weight and alcohol use.6,52-56 In the United States, invasive breast cancer affects 1 in 8 women.50,52,57

Our screened population showed nearly 3 times as many women veterans were at an increased risk for breast cancer when compared with historical averages in US women. This difference may be based on a high rate of prior breast biopsies or positive family history, although a provocative study using the Surveillance, Epidemiology, and End Results database showed military women to have higher rates of breast cancer as well.9 Historically, Blacks are vastly understudied in clinical research with only 5% representation on a national level.5,58 The urban locations of both pilot sites (Washington, DC and Bronx, NY) allowed for the inclusion of minority patients in our study. We found that the rates of breast cancer in Black women veterans to be higher than seen nationally, possibly prompting further screening initiatives for this understudied population.

Our pilot study’s chemoprevention utilization (19%) was double the < 10% seen in the national population.33-35 The presence of a knowledgeable breast health practitioner to recruit study participants and offer personalized counseling to women veterans is a likely factor in overcoming barriers to chemopreventive acceptance. These participants may have been motivated to seek care for their high-risk status given a strong family history and prior breast biopsies.

Interestingly, a 3-fold higher PTSD rate was seen in this pilot population (29%) when compared with PTSD rates in the general female population (7-10%) and still one-third higher than the general population of women veterans (20%).45-47 Mental health, anxiety, and PTSD have been barriers to patients who sought treatment and have been implicated in poor adherence to medical advice.48,49 Cancer screening can induce anxiety in patients, and it may be amplified in patients with PTSD. It was remarkable that although adherence with screening recommendations is decreased when PTSD is present, our patient population demonstrated a higher rate of screening adherence.

Women who are seen at the VA often use multiple clinical specialties, and their EMR can be accessed across VA medical centers nationwide. Therefore, identifying women veterans who meet screening criteria is easily attainable within the VA.

When comparing high-risk with average risk women, the lifestyle results (BMI, smoking history, exercise and consumption of fruits, vegetables and alcohol) were essentially the same. Lifestyle factors were similar to national population rates and were unlikely to impact risk levels.

Limitations

Study limitations included a high number of self-referrals and the large percentage of patients with a family history of breast cancer, making them more likely to seek screening. The higher-than-average risk of breast cancer may be driven by a high rate of breast biopsies and a strong family history. Lifestyle metrics could not be accurately compared to other national assessments of lifestyle factors due to the difference in data points that we used or the format of our questions.

 

 

Conclusions

As the number of women veterans increases and the incidence of breast cancer in women veterans rise, chemoprevention options should follow national guidelines. To our knowledge, this is the only oncology study with 60% Black women veterans. This study had a higher participation rate for Black women veterans than is typically seen in national research studies and shows the VA to be a germane source for further understanding of an understudied population that may benefit from increased screening for breast cancer.

A team-based, multidisciplinary model that meets the unique healthcare needs of women veterans results in a patient-centric delivery of care for assessing breast cancer risk status and prevention options. This model can be replicated nationally by directing primary care physicians and women’s health practitioners to a risk-assessment questionnaire and referring high-risk women for appropriate preventative care. Given that these results show chemoprevention adherence rates doubled those seen nationally, perhaps techniques used within this VA pilot study may be adapted to decrease breast cancer incidence nationally.

Since the rate of PTSD among women veterans is triple the national average, we would expect adherence rates to be lower in our patient cohort. However, the multidisciplinary approach we used in this study (eg, 1:1 consultation with oncologist; genetic counseling referrals; mental health support available), may have improved adherence rates. Perhaps the high rates of PTSD seen in the VA patient population can be a useful way to explore patient adherence rates in those with mental illness and medical conditions.

Future research with a larger cohort may lead to greater insight into the correlation between PTSD and adherence to treatment. Exploring the connection between breast cancer, epigenetics, and specific military service-related exposures could be an area of analysis among this veteran population exhibiting increased breast cancer rates. VAMCs are situated in rural, suburban, and urban locations across the United States and offers a diverse socioeconomic and ethnic patient population for inclusion in clinical investigations. Women veterans make up a small subpopulation of women in the United States, but it is worth considering VA patients as an untapped resource for research collaboration.

Acknowledgements

The authors thank Steven Sanchez and Marissa Vallette, PhD, Breast Health Research Group. This research project was approved by the James J. Peters VA Medical Center Quality Executive Committee and the Washington, DC VA Medical Center Institutional Review Board. This work was supported by the US Department of Veterans Affairs. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author disclosures

The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

References

1. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics. The past, present and future of women veterans. Published February 2017. Accessed April 28, 2021. https://www.va.gov/vetdata/docs/specialreports/women_veterans_2015_final.pdf.

2. Frayne SM, Carney DV, Bastian L, et al. The VA Women’s Health Practice-Based Research Network: amplifying women veterans’ voices in VA research. J Gen Intern Med. 2013;28 Suppl 2(Suppl 2):S504-S509. doi:10.1007/s11606-013-2476-3

3. US Department of Veterans Affairs, Veterans Health Administration, Women’s Health Evaluation Initiative, Women Veterans Health Strategic Health Care Group. Sourcebook: women veterans in the Veterans Health Administration. Volume 1: Sociodemographic characteristics and use of VHA care. Published December 2010. Accessed April 12, 2021. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=2455

4. Bean-Mayberry B, Yano EM, Bayliss N, Navratil J, Weisman CS, Scholle SH. Federally funded comprehensive women’s health centers: leading innovation in women’s healthcare delivery. J Womens Health (Larchmt). 2007;16(9):1281-1290. doi:10.1089/jwh.2006.0284

5. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics.VA utilization profile FY 2016. Published November 2017. Accessed April 12, 2021. https://www.va.gov/vetdata/docs/QuickFacts/VA_Utilization_Profile.PDF

6. Ekenga CC, Parks CG, Sandler DP. Chemical exposures in the workplace and breast cancer risk: a prospective cohort study. Int J Cancer. 2015;137(7):1765-1774. doi:10.1002/ijc.29545

7. Rennix CP, Quinn MM, Amoroso PJ, Eisen EA, Wegman DH. Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds. Am J Ind Med. 2005;48(3):157-167. doi:10.1002/ajim.20201

8. Ritz B. Cancer mortality among workers exposed to chemicals during uranium processing. J Occup Environ Med. 1999;41(7):556-566. doi:10.1097/00043764-199907000-00004

9. Zhu K, Devesa SS, Wu H, et al. Cancer incidence in the U.S. military population: comparison with rates from the SEER program. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1740-1745. doi:10.1158/1055-9965.EPI-09-0041

10. Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older [published correction appears in J Clin Oncol. 2013 Nov 10;31(32):4167]. J Clin Oncol. 2011;29(17):2327-2333. doi:10.1200/JCO.2010.33.0258

11. Greene, H. Cancer prevention, screening and early detection. In: Gobel BH, Triest-Robertson S, Vogel WH, eds. Advanced Oncology Nursing Certification Review and Resource Manual. 3rd ed. Oncology Nursing Society; 2016:1-34. https://www.ons.org/sites/default/files/publication_pdfs/2%20ADVPrac%20chapter%201.pdf

12. National Comprehensive Cancer Network. NCCN Breast Cancer Risk Reduction. Version 1.2021 NCCN Clinical Practice Guidelines in Oncology. Updated March 24, 2021 Accessed April 12, 2021. https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf

13. US Preventive Services Task Force. Breast cancer: Medications use to reduce risk. Updated September 3, 2019. Accessed April 12, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-medications-for-risk-reduction

14. Moyer VA; U.S. Preventive Services Task Force. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(10):698-708. doi:10.7326/0003-4819-159-10-201311190-00717

15. Boucher JE. Chemoprevention: an overview of pharmacologic agents and nursing considerations. Clin J Oncol Nurs. 2018;22(3):350-353. doi:10.1188/18.CJON.350-353

16. Nichols HB, Stürmer T, Lee VS, et al. Breast cancer chemoprevention in an integrated health care setting. JCO Clin Cancer Inform. 2017;1:1-12. doi:10.1200/CCI.16.00059

17. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(11):1362-1389. doi:10.6004/jnccn.2018.0083

18. Visvanathan K, Hurley P, Bantug E, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline [published correction appears in J Clin Oncol. 2013 Dec 1;31(34):4383]. J Clin Oncol. 2013;31(23):2942-2962. doi:10.1200/JCO.2013.49.3122

19. Sealy-Jefferson S, Roseland ME, Cote ML, et al. rural-urban residence and stage at breast cancer diagnosis among postmenopausal women: The Women’s Health Initiative. J Womens Health (Larchmt). 2019;28(2):276-283. doi:10.1089/jwh.2017.6884

20. Holder KA. Veterans in rural America: 2011-2015. Published January 25, 2017. Accessed April 12, 2021. https://www.census.gov/library/publications/2017/acs/acs-36.html

21. Owens WL, Gallagher TJ, Kincheloe MJ, Ruetten VL. Implementation in a large health system of a program to identify women at high risk for breast cancer. J Oncol Pract. 2011;7(2):85-88. doi:10.1200/JOP.2010.000107

2. Pivot X, Viguier J, Touboul C, et al. Breast cancer screening controversy: too much or not enough?. Eur J Cancer Prev. 2015;24 Suppl:S73-S76. doi:10.1097/CEJ.0000000000000145

23. Bidassie B, Kovach A, Vallette MA, et al. Breast Cancer risk assessment and chemoprevention use among veterans affairs primary care providers: a national online survey. Mil Med. 2020;185(3-4):512-518. doi:10.1093/milmed/usz291

24. Brewster AM, Davidson NE, McCaskill-Stevens W. Chemoprevention for breast cancer: overcoming barriers to treatment. Am Soc Clin Oncol Educ Book. 2012;85-90. doi:10.14694/EdBook_AM.2012.32.152

25. Meyskens FL Jr, Curt GA, Brenner DE, et al. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic. Cancer Prev Res (Phila). 2011;4(3):311-323. doi:10.1158/1940-6207.CAPR-09-0014

26. Tice JA, Kerlikowske K. Screening and prevention of breast cancer in primary care. Prim Care. 2009;36(3):533-558. doi:10.1016/j.pop.2009.04.003

27. Vogel VG. Selective estrogen receptor modulators and aromatase inhibitors for breast cancer chemoprevention. Curr Drug Targets. 2011;12(13):1874-1887. doi:10.2174/138945011798184164

28. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial [published correction appears in JAMA. 2006 Dec 27;296(24):2926] [published correction appears in JAMA. 2007 Sep 5;298(9):973]. JAMA. 2006;295(23):2727-2741. doi:10.1001/jama.295.23.joc60074

29. Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22(10):3230-3235. doi:10.1245/s10434-015-4715-9

30. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial [published correction appears in Lancet. 2014 Mar 22;383(9922):1040] [published correction appears in Lancet. 2017 Mar 11;389(10073):1010]. Lancet. 2014;383(9922):1041-1048. doi:10.1016/S0140-6736(13)62292-8

31. Bozovic-Spasojevic I, Azambuja E, McCaskill-Stevens W, Dinh P, Cardoso F. Chemoprevention for breast cancer. Cancer Treat Rev. 2012;38(5):329-339. doi:10.1016/j.ctrv.2011.07.005

32. Gabriel EM, Jatoi I. Breast cancer chemoprevention. Expert Rev Anticancer Ther. 2012;12(2):223-228. doi:10.1586/era.11.206

<--pagebreak-->

33. Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention?. NPJ Breast Cancer. 2017;3:20. Published 2017 May 19. doi:10.1038/s41523-017-0021-y

34. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. J Clin Oncol. 2010;28(18):3090-3095. doi:10.1200/JCO.2009.27.8077

35. Smith SG, Sestak I, Forster A, et al. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):575-590. doi:10.1093/annonc/mdv590

36. Grann VR, Patel PR, Jacobson JS, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat. 2011 Feb;125(3):837-847. doi:10.1007/s10549-010-1043-4

37. Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women [published correction appears in N Engl J Med. 2011 Oct 6;365(14):1361]. N Engl J Med. 2011;364(25):2381-2391. doi:10.1056/NEJMoa1103507

38. Kmietowicz Z. Five in six women reject drugs that could reduce their risk of breast cancer. BMJ. 2015;351:h6650. Published 2015 Dec 8. doi:10.1136/bmj.h6650

39. Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 2009;151(10):703-235. doi:10.7326/0003-4819-151-10-200911170-00147

40. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core needle and open surgery biopsy for diagnosis of breast lesions: an update to the 2009 report. Published September 2014. Accessed April 12, 2021. https://www.ncbi.nlm.nih.gov/books/NBK246878

41. National Cancer Institute. Genetics of breast and ovarian cancer (PDQ)—health profession version. Updated February 12, 2021. Accessed April 12, 2021. http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional

42. US Department of Health and Human Services. National Institutes of Health, National Institute of Environmental Health Sciences The sister study. Accessed April 12, 2021. https://sisterstudy.niehs.nih.gov/english/NIEHS.htm

43. Tutt A, Ashworth A. Can genetic testing guide treatment in breast cancer?. Eur J Cancer. 2008;44(18):2774-2780. doi:10.1016/j.ejca.2008.10.009

44. Katz SJ, Ward KC, Hamilton AS, et al. Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer. J Clin Oncol. 2018;36(12):1218-1224. doi:10.1200/JCO.2017.76.2369

45. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in adults? Updated October 17, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_adults.asp

46. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in women? Updated October 16, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_women.asp

47. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in veterans? Updated September 24, 2018. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_veterans.asp

48. Lindberg NM, Wellisch D. Anxiety and compliance among women at high risk for breast cancer. Ann Behav Med. 2001;23(4):298-303. doi:10.1207/S15324796ABM2304_9

49. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107. doi:10.1001/archinte.160.14.2101

50. Centers for Disease Control and Prevention. MMWR appendix: breast cancer rates among black women and white women. Updated October 13, 2016. Accessed April 12, 2021. https://www.cdc.gov/cancer/breast/statistics/trends_invasive.htm

51. Richardson LC, Henley SJ, Miller JW, Massetti G, Thomas CC. Patterns and trends in age-specific black-white differences in breast cancer incidence and mortality - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2016;65(40):1093-1098. Published 2016 Oct 14. doi:10.15585/mmwr.mm6540a1

52. Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007;109(12 Suppl):2667-2711. doi:10.1002/cncr.22655

53. Brophy JT, Keith MM, Watterson A, et al. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. Environ Health. 2012;11:87. Published 2012 Nov 19. doi:10.1186/1476-069X-11-87

54. Labrèche F, Goldberg MS, Valois MF, Nadon L. Postmenopausal breast cancer and occupational exposures. Occup Environ Med. 2010;67(4):263-269. doi:10.1136/oem.2009.049817

55. National Institute of Environmental Health Sciences, Interagency Breast Cancer & Environmental Research Coordinating Committee. Breast cancer and the environment: prioritizing prevention. Updated March 8, 2013. Accessed April 12, 2021. https://www.niehs.nih.gov/about/boards/ibcercc/index.cfm

56. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women [published correction appears in J Natl Cancer Inst. 2008 Aug 6;100(15):1118] [published correction appears in J Natl Cancer Inst. 2008 Mar 5;100(5):373]. J Natl Cancer Inst. 2007;99(23):1782-1792. doi:10.1093/jnci/djm223

57. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.x

58. Braunstein JB, Sherber NS, Schulman SP, Ding EL, Powe NR. Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials. Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78

References

1. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics. The past, present and future of women veterans. Published February 2017. Accessed April 28, 2021. https://www.va.gov/vetdata/docs/specialreports/women_veterans_2015_final.pdf.

2. Frayne SM, Carney DV, Bastian L, et al. The VA Women’s Health Practice-Based Research Network: amplifying women veterans’ voices in VA research. J Gen Intern Med. 2013;28 Suppl 2(Suppl 2):S504-S509. doi:10.1007/s11606-013-2476-3

3. US Department of Veterans Affairs, Veterans Health Administration, Women’s Health Evaluation Initiative, Women Veterans Health Strategic Health Care Group. Sourcebook: women veterans in the Veterans Health Administration. Volume 1: Sociodemographic characteristics and use of VHA care. Published December 2010. Accessed April 12, 2021. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=2455

4. Bean-Mayberry B, Yano EM, Bayliss N, Navratil J, Weisman CS, Scholle SH. Federally funded comprehensive women’s health centers: leading innovation in women’s healthcare delivery. J Womens Health (Larchmt). 2007;16(9):1281-1290. doi:10.1089/jwh.2006.0284

5. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics.VA utilization profile FY 2016. Published November 2017. Accessed April 12, 2021. https://www.va.gov/vetdata/docs/QuickFacts/VA_Utilization_Profile.PDF

6. Ekenga CC, Parks CG, Sandler DP. Chemical exposures in the workplace and breast cancer risk: a prospective cohort study. Int J Cancer. 2015;137(7):1765-1774. doi:10.1002/ijc.29545

7. Rennix CP, Quinn MM, Amoroso PJ, Eisen EA, Wegman DH. Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds. Am J Ind Med. 2005;48(3):157-167. doi:10.1002/ajim.20201

8. Ritz B. Cancer mortality among workers exposed to chemicals during uranium processing. J Occup Environ Med. 1999;41(7):556-566. doi:10.1097/00043764-199907000-00004

9. Zhu K, Devesa SS, Wu H, et al. Cancer incidence in the U.S. military population: comparison with rates from the SEER program. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1740-1745. doi:10.1158/1055-9965.EPI-09-0041

10. Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older [published correction appears in J Clin Oncol. 2013 Nov 10;31(32):4167]. J Clin Oncol. 2011;29(17):2327-2333. doi:10.1200/JCO.2010.33.0258

11. Greene, H. Cancer prevention, screening and early detection. In: Gobel BH, Triest-Robertson S, Vogel WH, eds. Advanced Oncology Nursing Certification Review and Resource Manual. 3rd ed. Oncology Nursing Society; 2016:1-34. https://www.ons.org/sites/default/files/publication_pdfs/2%20ADVPrac%20chapter%201.pdf

12. National Comprehensive Cancer Network. NCCN Breast Cancer Risk Reduction. Version 1.2021 NCCN Clinical Practice Guidelines in Oncology. Updated March 24, 2021 Accessed April 12, 2021. https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf

13. US Preventive Services Task Force. Breast cancer: Medications use to reduce risk. Updated September 3, 2019. Accessed April 12, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-medications-for-risk-reduction

14. Moyer VA; U.S. Preventive Services Task Force. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(10):698-708. doi:10.7326/0003-4819-159-10-201311190-00717

15. Boucher JE. Chemoprevention: an overview of pharmacologic agents and nursing considerations. Clin J Oncol Nurs. 2018;22(3):350-353. doi:10.1188/18.CJON.350-353

16. Nichols HB, Stürmer T, Lee VS, et al. Breast cancer chemoprevention in an integrated health care setting. JCO Clin Cancer Inform. 2017;1:1-12. doi:10.1200/CCI.16.00059

17. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(11):1362-1389. doi:10.6004/jnccn.2018.0083

18. Visvanathan K, Hurley P, Bantug E, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline [published correction appears in J Clin Oncol. 2013 Dec 1;31(34):4383]. J Clin Oncol. 2013;31(23):2942-2962. doi:10.1200/JCO.2013.49.3122

19. Sealy-Jefferson S, Roseland ME, Cote ML, et al. rural-urban residence and stage at breast cancer diagnosis among postmenopausal women: The Women’s Health Initiative. J Womens Health (Larchmt). 2019;28(2):276-283. doi:10.1089/jwh.2017.6884

20. Holder KA. Veterans in rural America: 2011-2015. Published January 25, 2017. Accessed April 12, 2021. https://www.census.gov/library/publications/2017/acs/acs-36.html

21. Owens WL, Gallagher TJ, Kincheloe MJ, Ruetten VL. Implementation in a large health system of a program to identify women at high risk for breast cancer. J Oncol Pract. 2011;7(2):85-88. doi:10.1200/JOP.2010.000107

2. Pivot X, Viguier J, Touboul C, et al. Breast cancer screening controversy: too much or not enough?. Eur J Cancer Prev. 2015;24 Suppl:S73-S76. doi:10.1097/CEJ.0000000000000145

23. Bidassie B, Kovach A, Vallette MA, et al. Breast Cancer risk assessment and chemoprevention use among veterans affairs primary care providers: a national online survey. Mil Med. 2020;185(3-4):512-518. doi:10.1093/milmed/usz291

24. Brewster AM, Davidson NE, McCaskill-Stevens W. Chemoprevention for breast cancer: overcoming barriers to treatment. Am Soc Clin Oncol Educ Book. 2012;85-90. doi:10.14694/EdBook_AM.2012.32.152

25. Meyskens FL Jr, Curt GA, Brenner DE, et al. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic. Cancer Prev Res (Phila). 2011;4(3):311-323. doi:10.1158/1940-6207.CAPR-09-0014

26. Tice JA, Kerlikowske K. Screening and prevention of breast cancer in primary care. Prim Care. 2009;36(3):533-558. doi:10.1016/j.pop.2009.04.003

27. Vogel VG. Selective estrogen receptor modulators and aromatase inhibitors for breast cancer chemoprevention. Curr Drug Targets. 2011;12(13):1874-1887. doi:10.2174/138945011798184164

28. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial [published correction appears in JAMA. 2006 Dec 27;296(24):2926] [published correction appears in JAMA. 2007 Sep 5;298(9):973]. JAMA. 2006;295(23):2727-2741. doi:10.1001/jama.295.23.joc60074

29. Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22(10):3230-3235. doi:10.1245/s10434-015-4715-9

30. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial [published correction appears in Lancet. 2014 Mar 22;383(9922):1040] [published correction appears in Lancet. 2017 Mar 11;389(10073):1010]. Lancet. 2014;383(9922):1041-1048. doi:10.1016/S0140-6736(13)62292-8

31. Bozovic-Spasojevic I, Azambuja E, McCaskill-Stevens W, Dinh P, Cardoso F. Chemoprevention for breast cancer. Cancer Treat Rev. 2012;38(5):329-339. doi:10.1016/j.ctrv.2011.07.005

32. Gabriel EM, Jatoi I. Breast cancer chemoprevention. Expert Rev Anticancer Ther. 2012;12(2):223-228. doi:10.1586/era.11.206

<--pagebreak-->

33. Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention?. NPJ Breast Cancer. 2017;3:20. Published 2017 May 19. doi:10.1038/s41523-017-0021-y

34. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. J Clin Oncol. 2010;28(18):3090-3095. doi:10.1200/JCO.2009.27.8077

35. Smith SG, Sestak I, Forster A, et al. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):575-590. doi:10.1093/annonc/mdv590

36. Grann VR, Patel PR, Jacobson JS, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat. 2011 Feb;125(3):837-847. doi:10.1007/s10549-010-1043-4

37. Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women [published correction appears in N Engl J Med. 2011 Oct 6;365(14):1361]. N Engl J Med. 2011;364(25):2381-2391. doi:10.1056/NEJMoa1103507

38. Kmietowicz Z. Five in six women reject drugs that could reduce their risk of breast cancer. BMJ. 2015;351:h6650. Published 2015 Dec 8. doi:10.1136/bmj.h6650

39. Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 2009;151(10):703-235. doi:10.7326/0003-4819-151-10-200911170-00147

40. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core needle and open surgery biopsy for diagnosis of breast lesions: an update to the 2009 report. Published September 2014. Accessed April 12, 2021. https://www.ncbi.nlm.nih.gov/books/NBK246878

41. National Cancer Institute. Genetics of breast and ovarian cancer (PDQ)—health profession version. Updated February 12, 2021. Accessed April 12, 2021. http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional

42. US Department of Health and Human Services. National Institutes of Health, National Institute of Environmental Health Sciences The sister study. Accessed April 12, 2021. https://sisterstudy.niehs.nih.gov/english/NIEHS.htm

43. Tutt A, Ashworth A. Can genetic testing guide treatment in breast cancer?. Eur J Cancer. 2008;44(18):2774-2780. doi:10.1016/j.ejca.2008.10.009

44. Katz SJ, Ward KC, Hamilton AS, et al. Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer. J Clin Oncol. 2018;36(12):1218-1224. doi:10.1200/JCO.2017.76.2369

45. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in adults? Updated October 17, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_adults.asp

46. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in women? Updated October 16, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_women.asp

47. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in veterans? Updated September 24, 2018. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_veterans.asp

48. Lindberg NM, Wellisch D. Anxiety and compliance among women at high risk for breast cancer. Ann Behav Med. 2001;23(4):298-303. doi:10.1207/S15324796ABM2304_9

49. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107. doi:10.1001/archinte.160.14.2101

50. Centers for Disease Control and Prevention. MMWR appendix: breast cancer rates among black women and white women. Updated October 13, 2016. Accessed April 12, 2021. https://www.cdc.gov/cancer/breast/statistics/trends_invasive.htm

51. Richardson LC, Henley SJ, Miller JW, Massetti G, Thomas CC. Patterns and trends in age-specific black-white differences in breast cancer incidence and mortality - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2016;65(40):1093-1098. Published 2016 Oct 14. doi:10.15585/mmwr.mm6540a1

52. Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007;109(12 Suppl):2667-2711. doi:10.1002/cncr.22655

53. Brophy JT, Keith MM, Watterson A, et al. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. Environ Health. 2012;11:87. Published 2012 Nov 19. doi:10.1186/1476-069X-11-87

54. Labrèche F, Goldberg MS, Valois MF, Nadon L. Postmenopausal breast cancer and occupational exposures. Occup Environ Med. 2010;67(4):263-269. doi:10.1136/oem.2009.049817

55. National Institute of Environmental Health Sciences, Interagency Breast Cancer & Environmental Research Coordinating Committee. Breast cancer and the environment: prioritizing prevention. Updated March 8, 2013. Accessed April 12, 2021. https://www.niehs.nih.gov/about/boards/ibcercc/index.cfm

56. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women [published correction appears in J Natl Cancer Inst. 2008 Aug 6;100(15):1118] [published correction appears in J Natl Cancer Inst. 2008 Mar 5;100(5):373]. J Natl Cancer Inst. 2007;99(23):1782-1792. doi:10.1093/jnci/djm223

57. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.x

58. Braunstein JB, Sherber NS, Schulman SP, Ding EL, Powe NR. Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials. Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78

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Achieving Excellence in Hepatitis B Virus Care for Veterans in the VHA (FULL)

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Achieving Excellence in Hepatitis B Virus Care for Veterans in the VHA
Enhancing care of veterans infected with hepatitis B virus who are in VHA care includes providingclinical guidance, informatics tools, patient monitoring, and continuous evaluation of care.

Hepatitis B is a viral infection caused by the hepatitis B virus (HBV), which is transmitted through percutaneous (ie, puncture through the skin) or mucosal (ie, direct contact with mucous membranes) exposure to infectious blood or body fluids. Hepatitis B virus can cause chronic infection, resulting in cirrhosis of the liver, liver cancer, liver failure, and death. Persons with chronic infection also serve as the main reservoir for continued HBV transmission.1

Individuals at highest risk for infection include those born in geographic regions with a high prevalence of HBV, those with sexual partners or household contacts with chronic HBV infection, men who have sex with men (MSM), those with HIV, and individuals who inject drugs. Pregnant women also are a population of concern given the potential for perinatal transmission.2

About 850,000 to 2.2 million people in the US (about 0.3% of the civilian US population) are chronically infected with HBV.3 The prevalence of chronic HBV is much higher (10%-19%) among Asian Americans, those of Pacific Island descent, and other immigrant populations from highly endemic countries.4 In the US, HBV is responsible for 2,000 to 4,000 preventable deaths annually, primarily from cirrhosis, liver cancer, and hepatic failure.4 In the civilian US population, reported cases of acute HBV decreased 0.3% from 2011 to 2012, increased 5.4% in 2013 with an 8.5% decrease in 2014, and a 20.7% increase in 2015.4 Injection drug use is likely driving the most recent increase.5

Not all individuals exposed to HBV will develop chronic infection, and the risk of chronic HBV infection depends on an individual’s age at the time of exposure. For example, about 95% of infants exposed to HBV perinatally will develop a chronic infection compared with 5% of exposed adults.6 Of those with chronic HBV, a small proportion will develop cirrhosis and/or hepatocellular carcinoma (HCC) with increasing risk as viral DNA concentrations increase. Additional risk factors for cirrhosis include being older, male, having a persistently elevated alanine transaminase, viral superinfections, HBV reversion/reactivation, genotype, and various markers of disease severity (HCC).6 Of note, chronic HBV infection may cause HCC even in the absence of cirrhosis.7 In addition, immunosuppression (eg, from cancer chemotherapy) may allow HBV reactivation, which may result in fulminant hepatic failure. In the Veterans Health Affairs (VHA) health care system, about 17% of those with known chronic HBV also carry a diagnosis of cirrhosis.

Vaccination is the mainstay of efforts to prevent HBV infection. The first commercially available HBV vaccine was approved by the FDA in 1981, with subsequent FDA approval in 1986 of a vaccine manufactured using recombinant DNA technology.8 In 1991, the Advisory Committee on Immunization Practices (ACIP) recommended universal childhood vaccination for HBV, with subsequent recommendations for vaccination of adolescents and adults in high-risk groups in 1995, and in 1999 all remaining unvaccinated children aged ≤ 19 years.9 Military policy has been to provide hepatitis B immunization to personnel assigned to the Korean peninsula since 1986 and to all recruits since 2001.10

Following publication of an Institute of Medicine/National Academies of Sciences, Engineering, and Medicine (NASEM) report, in 2011 the US Department of Health and Human Services (HHS) released the first National Viral Hepatitis Action Plan.11 The current HHS Action Plan, along with the NASEM National Strategy for the Elimination of Hepatitis B and C: Phase Two Report, commissioned by the US Centers for Disease Control and Prevention (CDC), outlines a national strategy to prevent new viral hepatitis infections; reduce deaths and improve the health of people living with viral hepatitis; reduce viral hepatitis health disparities; and coordinate, monitor, and report on implementation of viral hepatitis activities.12 The VA is a critical partner in this federal collaborative effort to achieve excellence in viral hepatitis care.

In August 2016, the HIV, Hepatitis, and Related Conditions Programs in the VA Office of Specialty Care Services convened a National Hepatitis B Working Group consisting of VA subject matter experts (SMEs) and representatives from the VA Central Office stakeholder program offices, with a charge of developing a strategic plan to ensure excellence in HBV prevention, care, and management across the VHA. The task included addressing supportive processes and barriers at each level of the organization through a public health framework and using a population health management approach.

The VA National Strategic Plan for Excellence in HBV Care was focused on the following overarching aims:

  • Characterizing the current state of care for veterans with HBV in VA care;
  • Developing and disseminating clinical guidance on high-quality care for patients with HBV;
  • Developing population data and informatics tools to streamline the identification and monitoring of patients with chronic HBV; and
  • Evaluating VHA care for patients with HBV over time.
 

 

Care for Veterans With HBV at the VA

The VA health care system is America’s largest integrated health care system, providing care at 1,243 health care facilities, including 170 medical centers and 1,063 outpatient sites of care serving 9 million enrolled veterans each year.13 As of January 2018, there were 10,743 individuals with serologic evidence for chronic HBV infection in VA care, based on a definition of 2 or more detectable surface antigen (sAg) or hepatitis B DNA tests recorded at least 6 months apart.1 About 2,000 additional VA patients have a history of a single positive sAg test. These patients have unclear HBV status and require a second sAg test to determine whether they have a chronic infection.

The prevalence of HBV infection among veterans in VA care is slightly higher than that in the US civilian population at 0.4%.14 Studies of selected subpopulations of veterans have found high seropositivity of prior or chronic HBV infection among homeless veterans and veterans admitted to a psychiatric hospital.15,16 The data from 2015 suggest that homeless veterans have a chronic HBV infection rate of 1.0%.14 Of those with known chronic HBV infection, the plurality are white (40.4%) or African American (40.2%), male (92.4%), with a mean age of 59.9 (SD 12.0) years. According to National HIV, Hepatitis and Related Conditions Data and Analysis Group personal correspondence, the geographic territories with the largest chronic HBV caseload include the Southeast, Gulf Coast, and West Coast. As of January 2018, 1,210 veterans in care have HBV-related cirrhosis.

HBV Screening in VA

The current VA HBV screening guidelines follow those of the US Preventive Services Task Force (USPSTF).17 HBV screening is recommended for unvaccinated individuals in high-risk groups, such as patients with HIV or hepatitis C virus (HCV), those on hemodialysis, those with elevated alanine transaminase/aspartate transaminase of unknown etiology, those on immunosuppressive therapy, injection drug users, the MSM population, people with household contact with an HBV-infected person, people born to an HBV-infected mother, those with risk factors for HBV exposure prior to vaccination, pregnant women, and people born in highly endemic areas regardless of vaccination status.2 The VHA recommends against standardized risk assessment and laboratory screening for HBV infection in the asymptomatic general patient population. However, if risk factors become known during the course of providing usual clinical care, then laboratory screening should be considered.2

Of the 6.1 million VHA users in fiscal year (FY) 2016, 26% have received HBV testing, an increase from 21.8% in FY 2013, despite enrollment of nearly 500,000 new VA users since that time. Screening rates for HBV among veterans in VHA care with HIV and HCV are > 94%.18 The VHA screening rates for HBV for veterans receiving immunosuppressive therapy, who inject drugs, or who have sexually transmitted infection are estimated to be 43.9%, 53.5%, and 51.4%, respectively.18 Testing for HBV sAg in homeless US veterans is estimated at 52.8% using data from a 2015 prevalence study.14

HBV Care and VA Antiviral Treatment

In a study of an HBV care cascade, Serper and colleagues reviewed a cohort of veterans in the VA with HBV. About 50% of the patients with known chronic HBV in the VA system from 1999 to 2013 had received infectious diseases or gastroenterology/hepatology specialty care in the previous 2 years.19 Follow-up data from the National HIV, Hepatitis and Related Conditions Data and Analysis Group indicated that this remains the case: 52.3% of patients with documented chronic HBV had received specialty care from VA sources in the prior 2 years. Serper and colleagues also reported that among veterans in VHA care with chronic HBV infection and cirrhosis from 1999 to 2013, annual imaging was < 50%, and initiation of antiviral treatment was only 39%. Antiviral therapy and liver imaging were both independently associated with lower mortality for patients with HBV and cirrhosis.19

A review of studies that evaluated the delivery of care for patients with HBV in U.S. civilian populations, including retrospective reviews of private payer claims databases and chart reviews, the Kaiser Permanente claims database, and community gastrointestinal (GI) practice chart reviews, revealed similar practice patterns with those in the VA.20 Across the US, rates of antiviral therapy and HCC surveillance for those with HBV cirrhosis were low, ranging from 14% to 50% and 19% to 60%, respectively. Several of these studies also found that being seen by an HBV specialist was associated with improved care.20

Antiviral treatment of individuals with cirrhosis and chronic HBV infection can reduce the risk of progression to decompensated cirrhosis and liver cancer. Among current VA patients with HBV cirrhosis, 62.4% received at least 1 month of HBV antiviral medication in the prior year. Additionally, biannual liver imaging is recommended in this population to screen for the development of HCC. According to National HIV, Hepatitis and Related Conditions Data and Analysis Group personal correspondence, nationally, 51.2% of individuals with HBV cirrhosis had received at least one instance of liver imaging within the past 6 months, and 71.2% received imaging within the past 12 months.

 

 

Prevention of HBV Infection and Sequelae

Vaccination rates in the US vary by age group, with higher immunization rates among those born after 1991 than the rates of those born earlier. Data from the National Health and Nutrition Examination Survey from 1988 to 2012 reported 33% immunity among veterans aged < 50 years and 6% among those aged ≥ 50 years.21 In addition to individuals who received childhood vaccination in the 1990s, all new military recruits assigned to the Korean Peninsula were vaccinated for HBV as of 1986, and those joining the military after 2002 received mandatory vaccination.

The VA follows the ACIP/CDC hepatitis B immunization guidelines.22-24 The VA currently recommends HBV immunization among previously unvaccinated adults at increased risk of contracting HBV infection and for any other adult who is seeking protection from HBV infection. The VA also offers general recommendations for prevention of transmission between veterans with known chronic HBV to their household, sexual, or drug-using partners. Transmission prevention guidelines also provide recommendations for vaccination of pregnant women with HBV risk factors and women at risk for HBV infection during pregnancy.22

HBV Care Guidance

One of the core tasks of the VA National Hepatitis B Working Group, given its broad, multidisciplinary expertise in HBV, was developing general clinical guidelines for the provision of high-quality care for patients with HBV. The group reviewed current literature and scientific evidence on care for patients with HBV. The working group relied heavily on the VA’s national guidelines for HBV screening and immunization, which are based on recommendations from the USPSTF, ACIP, CDC, and professional societies. The professional society guidelines included the American Association for the Study of Liver Disease’s Guidelines for Treatment of Chronic Hepatitis B, the America College of Gastroenterology’s Practice Guidelines: Evaluation of Abnormal Liver Chemistries, the American Gastroenterological Association Institute’s Guidelines for Prevention and Treatment of Hepatitis B Reactivation during Immunosuppressive Drug Therapy, and CDC’s Guidelines for Screening Pregnant Women for HBV.19,22-27

The working group identified areas for HBV quality improvement that were consistent with the VA and professional guidelines, specific and measurable using VA data, clinically relevant, feasible, and achievable in a defined time period. Areas for targeted improvement will include testing for HBV among high-risk patients, increasing antiviral treatment and HCC surveillance of veterans with HBV-related cirrhosis, decreasing progression of chronic HBV to cirrhosis, and expanding prevention measures, such as immunization among those at high risk for HBV and prevention of HBV reactivation.

At a national level, development of specific and measurable quality of care indicators for HBV will aid in assessing gaps in care and developing strategies to address these gaps. A broader discussion of care for patients with HBV quality with front-line health care providers (HCPs) will be paired with increased education and providing clinical support tools for those HCPs and facilities without access to specialty GI services.

Clinical pharmacists will be critical targets for the dissemination of guidance for HBV care paired with clinical informatics support tools and clinical educational opportunities. As of 2015, there were about 7,700 clinical pharmacists in the VHA and 3,200 had a scope of practice that included prescribing authority. As a result, 20% of HCV prescriptions in the VA in fiscal year 2015 were written by a clinical pharmacy specialist.28 Since then, the VA has expanded the education and support of clinical pharmacists in the care of patients with HCV and advanced liver disease, making them uniquely suited to provide additional support for a complex, low-prevalence disease like HBV.

Identification and Monitoring

The HBV working group and the VA Viral Hepatitis Technical Advisory Group are working with field HCPs to develop several informatics tools to promote HBV case identification and quality monitoring. These groups identified several barriers to HBV case identification and monitoring. The following informatics tools are either available or in development to reduce these barriers:

  1. A local clinical case registry of patients with HBV infection based on ICD codes, which allows users to create custom reports to identify, monitor, and track care;
  2. Because of the risk of HBV reactivation in patients with chronic HBV infection who receive anti-CD20 agents, such as rituximab, a medication order check to improve HBV screening among veterans receiving anti-CD20 medication;
  3. Validated patient reports based on laboratory diagnosis of HBV, drawn from all results across the VHA since 1999, made available to all facilities;
  4. Interactive reports summarizing quality of care for patients with HBV infection, based on facility-level indicators in development by the national HBV working group, will be distributed and enable geographic comparison;
  5. An HBV immunization clinical reminder that will prompt frontline HCPs to test and vaccinate; and
  6. An HBV clinical dashboard that will enable HCPs and facilities to identify all their HBV-positive veterans and track their care and outcomes over time.
 

 

Evaluating VA Care for Patients with HBV

As indicators of quality of HBV care are refined for VA patients and the health care delivery system, guidance will be made broadly available to frontline HCPs and administrators. The HBV quality of care recommendations will be paired with a suite of clinical informatics tools and virtual educational trainings to ensure that VA HCPs and facilities can streamline care for patients with HBV infection as much as possible. Quality improvement will be measured nationally each year, and strategies to address persistent variability and gaps in care will be developed in collaboration with the VA SME’s, facilities, and HCPs.

Conclusion

Hepatitis B virus is at least as prevalent among veterans who are cared for at VA facilities as it is in the US civilian population. Although care for patients with HBV infection in the VA is similar to care for patients with HBV infection in the community, the VA recognizes areas for improved HBV prevention, testing, care, and treatment. The VA has begun a continuous quality improvement strategic plan to enhance the level of care for patients with HBV infection in VA care. Centralized coordination and communication of VA data combined with veteran- and field-centered policies and operational planning and execution will allow clinically relevant improvements in HBV diagnosis, treatment, and prevention among veterans served by VA.

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References

1. Centers for Disease Control and Prevention. Hepatitis B FAQs for health professionals: overview and statistics. https://www.cdc.gov/hepatitis/hbv/hbvfaq .htm#overview. Updated January 11, 2018. Accessed on February 12, 2018.

2. USDepartment of Veterans Affairs. National clinical preventive service guidance statements: hepatitis B screening. http://vaww.prevention.va.gov/CPS/Screen ing_for_Hepatitis_B.asp. Published August 11, 2016. [Nonpublic document; source not verified.]

3. Centers for Disease Control and Prevention. Surveillance for viral hepatitis—United States, 2015. https://www.cdc.gov/hepatitis/statistics/2015surveillance/index.htm. Updated June 19, 2017. Accessed February 12, 2018.

4. Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49(suppl 5):S28-S34.

5. Harris AM, Iqbal K, Schillie S, et al. Increases in acute hepatitis B virus infections— Kentucky, Tennessee, and West Virginia, 2006-2013. MMWR Morb Mortal Wkly Rep. 2016;65(3):47-50.

6. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373(9663):582-592.

7. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118-1127.

8. Weinbaum CM, Williams I, Mast EE, et al; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.

9. Centers for Disease Control and Prevention. Achievements in public health: hepatitis B vaccination—United States, 1982-2002. MMWR. 2002;51(25):549-552, 563.

10. Grabenstein JD, Pittman PR, Greenwood JT, Engler RJ. Immunization to protect the US Armed Forces: heritage, current practice, and prospects. Epidemiol Rev. 2006;28:3-26.

11. Colvin HM, Mitchell AE, eds; Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: National Academies Press; 2010.

12. National Academies of Sciences, Engineering, and Medicine. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report. Washington, DC: National Academies Press; 2017.

13. US Department of Veterans Affairs. Providing health care for veterans. https://www.va.gov/health. Updated February 20, 2018. Accessed February 22, 2018.

14. Noska AJ, Belperio PS, Loomis TP, O’Toole TP, Backus LI. Prevalence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus among homeless and nonhomeless United States veterans. Clin Infect Dis. 2017;65(2):252-258.

15. Gelberg L, Robertson MJ, Leake B, et al. Hepatitis B among homeless and other impoverished US military veterans in residential care in Los Angeles. Public Health. 2001;115(4):286-291.

16. Tabibian JH, Wirshing DA, Pierre JM, et al. Hepatitis B and C among veterans in a psychiatric ward. Dig Dis Sci. 2008;53(6):1693-1698

17. US Preventive Services Task Force. Final recommendation statement: screening for hepatitis B virus infection in nonpregnant adolescents and adults. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-b-virus-infection-screening-2014. Published May 2014. Updated February 2018. Accessed February 22, 2018.

18. Backus LI, Belperio PS, Loomis TP, Han SH, Mole LA. Screening for and prevalence of hepatitis B virus infection among high-risk veterans under the care of the U.S. Department of Veterans Affairs: a case report. Ann Intern Med. 2014;161(12):926-928.

19. Serper M, Choi G, Forde KA, Kaplan DE. Care delivery and outcomes among US veterans with hepatitis B: a national cohort study. Hepatology. 2016;63(6):1774-1782.

20. Mellinger J, Fontana RJ. Quality of care metrics in chronic hepatitis B. Hepatology. 2016;63(6):1755-1758.

21. Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63(2):388-397.

22. US Department of Veterans Affairs. National Clinical Preventive Service Guidance Statements: Hepatitis B Immunization. http://vaww.prevention.va.gov/CPS/Hepatitis_B_Immunization.asp. Nonpublic document. Source not verified.

23. Advisory Committee on Immunization Practices (ACIP). Recommended immunization schedule for adults aged 19 years or older, United States, 2017. https://www.cdc.gov/vaccines/schedules/hcp/adult.html. Accessed February 12, 2018.

24. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2018;67(1):1-31.

25. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283.

26. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.

27. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT; American Gastroenterological Association Institute. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215-219, quiz e16-e17.

28. Ourth H, Groppi J, Morreale AP, Quicci-Roberts K. Clinical pharmacist prescribing activities in the Veterans Health Administration. Am J Health Syst Pharm. 2016;73(18):1406-1415.

Author and Disclosure Information

Dr. Ross is Director and Dr. Chartier is the Deputy Director and the National Infectious Diseases Officer for the Veterans Health Administration (VHA) Office of Specialty Care Services, HIV, Hepatitis, and Related Conditions Programs (HHRC). Dr. Morgan is the Director of the HHRC National Hepatitis Resource Center; Chief, Gastroenterology at VA Long Beach Healthcare System in California; and Professor in the Division of Gastroenterology at University of California, Irvine. Dr. Lowy is a Data Analyst for the HHRC Data and Analytics Group and Data Analyst for Health Services Research and Development at VA Puget Sound Healthcare System. Dr. Beste is a Staff Physician and the Director of the VA National Liver Disease Database at VA Puget Sound Healthcare System, the Director of the HHRC Data Analytics Group, and Assistant Professor of Medicine in the Division of General Internal Medicine at the University of Washington in Seattle. Dr. Maier is a Staff Physician in the Infectious Diseases Section at the VA Portland Healthcare System and an Assistant Professor at Oregon Health and Sciences University in the Division of Infectious Diseases, both in Portland. Ms. Hoffman-Högg is National Program Manager for Prevention Policy at VHA National Center for Health Promotion and Disease Prevention in Durham, North Carolina.
Correspondence: Dr. Chartier (maggie.chartier@va.gov).

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

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Author and Disclosure Information

Dr. Ross is Director and Dr. Chartier is the Deputy Director and the National Infectious Diseases Officer for the Veterans Health Administration (VHA) Office of Specialty Care Services, HIV, Hepatitis, and Related Conditions Programs (HHRC). Dr. Morgan is the Director of the HHRC National Hepatitis Resource Center; Chief, Gastroenterology at VA Long Beach Healthcare System in California; and Professor in the Division of Gastroenterology at University of California, Irvine. Dr. Lowy is a Data Analyst for the HHRC Data and Analytics Group and Data Analyst for Health Services Research and Development at VA Puget Sound Healthcare System. Dr. Beste is a Staff Physician and the Director of the VA National Liver Disease Database at VA Puget Sound Healthcare System, the Director of the HHRC Data Analytics Group, and Assistant Professor of Medicine in the Division of General Internal Medicine at the University of Washington in Seattle. Dr. Maier is a Staff Physician in the Infectious Diseases Section at the VA Portland Healthcare System and an Assistant Professor at Oregon Health and Sciences University in the Division of Infectious Diseases, both in Portland. Ms. Hoffman-Högg is National Program Manager for Prevention Policy at VHA National Center for Health Promotion and Disease Prevention in Durham, North Carolina.
Correspondence: Dr. Chartier (maggie.chartier@va.gov).

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Author and Disclosure Information

Dr. Ross is Director and Dr. Chartier is the Deputy Director and the National Infectious Diseases Officer for the Veterans Health Administration (VHA) Office of Specialty Care Services, HIV, Hepatitis, and Related Conditions Programs (HHRC). Dr. Morgan is the Director of the HHRC National Hepatitis Resource Center; Chief, Gastroenterology at VA Long Beach Healthcare System in California; and Professor in the Division of Gastroenterology at University of California, Irvine. Dr. Lowy is a Data Analyst for the HHRC Data and Analytics Group and Data Analyst for Health Services Research and Development at VA Puget Sound Healthcare System. Dr. Beste is a Staff Physician and the Director of the VA National Liver Disease Database at VA Puget Sound Healthcare System, the Director of the HHRC Data Analytics Group, and Assistant Professor of Medicine in the Division of General Internal Medicine at the University of Washington in Seattle. Dr. Maier is a Staff Physician in the Infectious Diseases Section at the VA Portland Healthcare System and an Assistant Professor at Oregon Health and Sciences University in the Division of Infectious Diseases, both in Portland. Ms. Hoffman-Högg is National Program Manager for Prevention Policy at VHA National Center for Health Promotion and Disease Prevention in Durham, North Carolina.
Correspondence: Dr. Chartier (maggie.chartier@va.gov).

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Enhancing care of veterans infected with hepatitis B virus who are in VHA care includes providingclinical guidance, informatics tools, patient monitoring, and continuous evaluation of care.
Enhancing care of veterans infected with hepatitis B virus who are in VHA care includes providingclinical guidance, informatics tools, patient monitoring, and continuous evaluation of care.

Hepatitis B is a viral infection caused by the hepatitis B virus (HBV), which is transmitted through percutaneous (ie, puncture through the skin) or mucosal (ie, direct contact with mucous membranes) exposure to infectious blood or body fluids. Hepatitis B virus can cause chronic infection, resulting in cirrhosis of the liver, liver cancer, liver failure, and death. Persons with chronic infection also serve as the main reservoir for continued HBV transmission.1

Individuals at highest risk for infection include those born in geographic regions with a high prevalence of HBV, those with sexual partners or household contacts with chronic HBV infection, men who have sex with men (MSM), those with HIV, and individuals who inject drugs. Pregnant women also are a population of concern given the potential for perinatal transmission.2

About 850,000 to 2.2 million people in the US (about 0.3% of the civilian US population) are chronically infected with HBV.3 The prevalence of chronic HBV is much higher (10%-19%) among Asian Americans, those of Pacific Island descent, and other immigrant populations from highly endemic countries.4 In the US, HBV is responsible for 2,000 to 4,000 preventable deaths annually, primarily from cirrhosis, liver cancer, and hepatic failure.4 In the civilian US population, reported cases of acute HBV decreased 0.3% from 2011 to 2012, increased 5.4% in 2013 with an 8.5% decrease in 2014, and a 20.7% increase in 2015.4 Injection drug use is likely driving the most recent increase.5

Not all individuals exposed to HBV will develop chronic infection, and the risk of chronic HBV infection depends on an individual’s age at the time of exposure. For example, about 95% of infants exposed to HBV perinatally will develop a chronic infection compared with 5% of exposed adults.6 Of those with chronic HBV, a small proportion will develop cirrhosis and/or hepatocellular carcinoma (HCC) with increasing risk as viral DNA concentrations increase. Additional risk factors for cirrhosis include being older, male, having a persistently elevated alanine transaminase, viral superinfections, HBV reversion/reactivation, genotype, and various markers of disease severity (HCC).6 Of note, chronic HBV infection may cause HCC even in the absence of cirrhosis.7 In addition, immunosuppression (eg, from cancer chemotherapy) may allow HBV reactivation, which may result in fulminant hepatic failure. In the Veterans Health Affairs (VHA) health care system, about 17% of those with known chronic HBV also carry a diagnosis of cirrhosis.

Vaccination is the mainstay of efforts to prevent HBV infection. The first commercially available HBV vaccine was approved by the FDA in 1981, with subsequent FDA approval in 1986 of a vaccine manufactured using recombinant DNA technology.8 In 1991, the Advisory Committee on Immunization Practices (ACIP) recommended universal childhood vaccination for HBV, with subsequent recommendations for vaccination of adolescents and adults in high-risk groups in 1995, and in 1999 all remaining unvaccinated children aged ≤ 19 years.9 Military policy has been to provide hepatitis B immunization to personnel assigned to the Korean peninsula since 1986 and to all recruits since 2001.10

Following publication of an Institute of Medicine/National Academies of Sciences, Engineering, and Medicine (NASEM) report, in 2011 the US Department of Health and Human Services (HHS) released the first National Viral Hepatitis Action Plan.11 The current HHS Action Plan, along with the NASEM National Strategy for the Elimination of Hepatitis B and C: Phase Two Report, commissioned by the US Centers for Disease Control and Prevention (CDC), outlines a national strategy to prevent new viral hepatitis infections; reduce deaths and improve the health of people living with viral hepatitis; reduce viral hepatitis health disparities; and coordinate, monitor, and report on implementation of viral hepatitis activities.12 The VA is a critical partner in this federal collaborative effort to achieve excellence in viral hepatitis care.

In August 2016, the HIV, Hepatitis, and Related Conditions Programs in the VA Office of Specialty Care Services convened a National Hepatitis B Working Group consisting of VA subject matter experts (SMEs) and representatives from the VA Central Office stakeholder program offices, with a charge of developing a strategic plan to ensure excellence in HBV prevention, care, and management across the VHA. The task included addressing supportive processes and barriers at each level of the organization through a public health framework and using a population health management approach.

The VA National Strategic Plan for Excellence in HBV Care was focused on the following overarching aims:

  • Characterizing the current state of care for veterans with HBV in VA care;
  • Developing and disseminating clinical guidance on high-quality care for patients with HBV;
  • Developing population data and informatics tools to streamline the identification and monitoring of patients with chronic HBV; and
  • Evaluating VHA care for patients with HBV over time.
 

 

Care for Veterans With HBV at the VA

The VA health care system is America’s largest integrated health care system, providing care at 1,243 health care facilities, including 170 medical centers and 1,063 outpatient sites of care serving 9 million enrolled veterans each year.13 As of January 2018, there were 10,743 individuals with serologic evidence for chronic HBV infection in VA care, based on a definition of 2 or more detectable surface antigen (sAg) or hepatitis B DNA tests recorded at least 6 months apart.1 About 2,000 additional VA patients have a history of a single positive sAg test. These patients have unclear HBV status and require a second sAg test to determine whether they have a chronic infection.

The prevalence of HBV infection among veterans in VA care is slightly higher than that in the US civilian population at 0.4%.14 Studies of selected subpopulations of veterans have found high seropositivity of prior or chronic HBV infection among homeless veterans and veterans admitted to a psychiatric hospital.15,16 The data from 2015 suggest that homeless veterans have a chronic HBV infection rate of 1.0%.14 Of those with known chronic HBV infection, the plurality are white (40.4%) or African American (40.2%), male (92.4%), with a mean age of 59.9 (SD 12.0) years. According to National HIV, Hepatitis and Related Conditions Data and Analysis Group personal correspondence, the geographic territories with the largest chronic HBV caseload include the Southeast, Gulf Coast, and West Coast. As of January 2018, 1,210 veterans in care have HBV-related cirrhosis.

HBV Screening in VA

The current VA HBV screening guidelines follow those of the US Preventive Services Task Force (USPSTF).17 HBV screening is recommended for unvaccinated individuals in high-risk groups, such as patients with HIV or hepatitis C virus (HCV), those on hemodialysis, those with elevated alanine transaminase/aspartate transaminase of unknown etiology, those on immunosuppressive therapy, injection drug users, the MSM population, people with household contact with an HBV-infected person, people born to an HBV-infected mother, those with risk factors for HBV exposure prior to vaccination, pregnant women, and people born in highly endemic areas regardless of vaccination status.2 The VHA recommends against standardized risk assessment and laboratory screening for HBV infection in the asymptomatic general patient population. However, if risk factors become known during the course of providing usual clinical care, then laboratory screening should be considered.2

Of the 6.1 million VHA users in fiscal year (FY) 2016, 26% have received HBV testing, an increase from 21.8% in FY 2013, despite enrollment of nearly 500,000 new VA users since that time. Screening rates for HBV among veterans in VHA care with HIV and HCV are > 94%.18 The VHA screening rates for HBV for veterans receiving immunosuppressive therapy, who inject drugs, or who have sexually transmitted infection are estimated to be 43.9%, 53.5%, and 51.4%, respectively.18 Testing for HBV sAg in homeless US veterans is estimated at 52.8% using data from a 2015 prevalence study.14

HBV Care and VA Antiviral Treatment

In a study of an HBV care cascade, Serper and colleagues reviewed a cohort of veterans in the VA with HBV. About 50% of the patients with known chronic HBV in the VA system from 1999 to 2013 had received infectious diseases or gastroenterology/hepatology specialty care in the previous 2 years.19 Follow-up data from the National HIV, Hepatitis and Related Conditions Data and Analysis Group indicated that this remains the case: 52.3% of patients with documented chronic HBV had received specialty care from VA sources in the prior 2 years. Serper and colleagues also reported that among veterans in VHA care with chronic HBV infection and cirrhosis from 1999 to 2013, annual imaging was < 50%, and initiation of antiviral treatment was only 39%. Antiviral therapy and liver imaging were both independently associated with lower mortality for patients with HBV and cirrhosis.19

A review of studies that evaluated the delivery of care for patients with HBV in U.S. civilian populations, including retrospective reviews of private payer claims databases and chart reviews, the Kaiser Permanente claims database, and community gastrointestinal (GI) practice chart reviews, revealed similar practice patterns with those in the VA.20 Across the US, rates of antiviral therapy and HCC surveillance for those with HBV cirrhosis were low, ranging from 14% to 50% and 19% to 60%, respectively. Several of these studies also found that being seen by an HBV specialist was associated with improved care.20

Antiviral treatment of individuals with cirrhosis and chronic HBV infection can reduce the risk of progression to decompensated cirrhosis and liver cancer. Among current VA patients with HBV cirrhosis, 62.4% received at least 1 month of HBV antiviral medication in the prior year. Additionally, biannual liver imaging is recommended in this population to screen for the development of HCC. According to National HIV, Hepatitis and Related Conditions Data and Analysis Group personal correspondence, nationally, 51.2% of individuals with HBV cirrhosis had received at least one instance of liver imaging within the past 6 months, and 71.2% received imaging within the past 12 months.

 

 

Prevention of HBV Infection and Sequelae

Vaccination rates in the US vary by age group, with higher immunization rates among those born after 1991 than the rates of those born earlier. Data from the National Health and Nutrition Examination Survey from 1988 to 2012 reported 33% immunity among veterans aged < 50 years and 6% among those aged ≥ 50 years.21 In addition to individuals who received childhood vaccination in the 1990s, all new military recruits assigned to the Korean Peninsula were vaccinated for HBV as of 1986, and those joining the military after 2002 received mandatory vaccination.

The VA follows the ACIP/CDC hepatitis B immunization guidelines.22-24 The VA currently recommends HBV immunization among previously unvaccinated adults at increased risk of contracting HBV infection and for any other adult who is seeking protection from HBV infection. The VA also offers general recommendations for prevention of transmission between veterans with known chronic HBV to their household, sexual, or drug-using partners. Transmission prevention guidelines also provide recommendations for vaccination of pregnant women with HBV risk factors and women at risk for HBV infection during pregnancy.22

HBV Care Guidance

One of the core tasks of the VA National Hepatitis B Working Group, given its broad, multidisciplinary expertise in HBV, was developing general clinical guidelines for the provision of high-quality care for patients with HBV. The group reviewed current literature and scientific evidence on care for patients with HBV. The working group relied heavily on the VA’s national guidelines for HBV screening and immunization, which are based on recommendations from the USPSTF, ACIP, CDC, and professional societies. The professional society guidelines included the American Association for the Study of Liver Disease’s Guidelines for Treatment of Chronic Hepatitis B, the America College of Gastroenterology’s Practice Guidelines: Evaluation of Abnormal Liver Chemistries, the American Gastroenterological Association Institute’s Guidelines for Prevention and Treatment of Hepatitis B Reactivation during Immunosuppressive Drug Therapy, and CDC’s Guidelines for Screening Pregnant Women for HBV.19,22-27

The working group identified areas for HBV quality improvement that were consistent with the VA and professional guidelines, specific and measurable using VA data, clinically relevant, feasible, and achievable in a defined time period. Areas for targeted improvement will include testing for HBV among high-risk patients, increasing antiviral treatment and HCC surveillance of veterans with HBV-related cirrhosis, decreasing progression of chronic HBV to cirrhosis, and expanding prevention measures, such as immunization among those at high risk for HBV and prevention of HBV reactivation.

At a national level, development of specific and measurable quality of care indicators for HBV will aid in assessing gaps in care and developing strategies to address these gaps. A broader discussion of care for patients with HBV quality with front-line health care providers (HCPs) will be paired with increased education and providing clinical support tools for those HCPs and facilities without access to specialty GI services.

Clinical pharmacists will be critical targets for the dissemination of guidance for HBV care paired with clinical informatics support tools and clinical educational opportunities. As of 2015, there were about 7,700 clinical pharmacists in the VHA and 3,200 had a scope of practice that included prescribing authority. As a result, 20% of HCV prescriptions in the VA in fiscal year 2015 were written by a clinical pharmacy specialist.28 Since then, the VA has expanded the education and support of clinical pharmacists in the care of patients with HCV and advanced liver disease, making them uniquely suited to provide additional support for a complex, low-prevalence disease like HBV.

Identification and Monitoring

The HBV working group and the VA Viral Hepatitis Technical Advisory Group are working with field HCPs to develop several informatics tools to promote HBV case identification and quality monitoring. These groups identified several barriers to HBV case identification and monitoring. The following informatics tools are either available or in development to reduce these barriers:

  1. A local clinical case registry of patients with HBV infection based on ICD codes, which allows users to create custom reports to identify, monitor, and track care;
  2. Because of the risk of HBV reactivation in patients with chronic HBV infection who receive anti-CD20 agents, such as rituximab, a medication order check to improve HBV screening among veterans receiving anti-CD20 medication;
  3. Validated patient reports based on laboratory diagnosis of HBV, drawn from all results across the VHA since 1999, made available to all facilities;
  4. Interactive reports summarizing quality of care for patients with HBV infection, based on facility-level indicators in development by the national HBV working group, will be distributed and enable geographic comparison;
  5. An HBV immunization clinical reminder that will prompt frontline HCPs to test and vaccinate; and
  6. An HBV clinical dashboard that will enable HCPs and facilities to identify all their HBV-positive veterans and track their care and outcomes over time.
 

 

Evaluating VA Care for Patients with HBV

As indicators of quality of HBV care are refined for VA patients and the health care delivery system, guidance will be made broadly available to frontline HCPs and administrators. The HBV quality of care recommendations will be paired with a suite of clinical informatics tools and virtual educational trainings to ensure that VA HCPs and facilities can streamline care for patients with HBV infection as much as possible. Quality improvement will be measured nationally each year, and strategies to address persistent variability and gaps in care will be developed in collaboration with the VA SME’s, facilities, and HCPs.

Conclusion

Hepatitis B virus is at least as prevalent among veterans who are cared for at VA facilities as it is in the US civilian population. Although care for patients with HBV infection in the VA is similar to care for patients with HBV infection in the community, the VA recognizes areas for improved HBV prevention, testing, care, and treatment. The VA has begun a continuous quality improvement strategic plan to enhance the level of care for patients with HBV infection in VA care. Centralized coordination and communication of VA data combined with veteran- and field-centered policies and operational planning and execution will allow clinically relevant improvements in HBV diagnosis, treatment, and prevention among veterans served by VA.

Click here to read the digital edition.

Hepatitis B is a viral infection caused by the hepatitis B virus (HBV), which is transmitted through percutaneous (ie, puncture through the skin) or mucosal (ie, direct contact with mucous membranes) exposure to infectious blood or body fluids. Hepatitis B virus can cause chronic infection, resulting in cirrhosis of the liver, liver cancer, liver failure, and death. Persons with chronic infection also serve as the main reservoir for continued HBV transmission.1

Individuals at highest risk for infection include those born in geographic regions with a high prevalence of HBV, those with sexual partners or household contacts with chronic HBV infection, men who have sex with men (MSM), those with HIV, and individuals who inject drugs. Pregnant women also are a population of concern given the potential for perinatal transmission.2

About 850,000 to 2.2 million people in the US (about 0.3% of the civilian US population) are chronically infected with HBV.3 The prevalence of chronic HBV is much higher (10%-19%) among Asian Americans, those of Pacific Island descent, and other immigrant populations from highly endemic countries.4 In the US, HBV is responsible for 2,000 to 4,000 preventable deaths annually, primarily from cirrhosis, liver cancer, and hepatic failure.4 In the civilian US population, reported cases of acute HBV decreased 0.3% from 2011 to 2012, increased 5.4% in 2013 with an 8.5% decrease in 2014, and a 20.7% increase in 2015.4 Injection drug use is likely driving the most recent increase.5

Not all individuals exposed to HBV will develop chronic infection, and the risk of chronic HBV infection depends on an individual’s age at the time of exposure. For example, about 95% of infants exposed to HBV perinatally will develop a chronic infection compared with 5% of exposed adults.6 Of those with chronic HBV, a small proportion will develop cirrhosis and/or hepatocellular carcinoma (HCC) with increasing risk as viral DNA concentrations increase. Additional risk factors for cirrhosis include being older, male, having a persistently elevated alanine transaminase, viral superinfections, HBV reversion/reactivation, genotype, and various markers of disease severity (HCC).6 Of note, chronic HBV infection may cause HCC even in the absence of cirrhosis.7 In addition, immunosuppression (eg, from cancer chemotherapy) may allow HBV reactivation, which may result in fulminant hepatic failure. In the Veterans Health Affairs (VHA) health care system, about 17% of those with known chronic HBV also carry a diagnosis of cirrhosis.

Vaccination is the mainstay of efforts to prevent HBV infection. The first commercially available HBV vaccine was approved by the FDA in 1981, with subsequent FDA approval in 1986 of a vaccine manufactured using recombinant DNA technology.8 In 1991, the Advisory Committee on Immunization Practices (ACIP) recommended universal childhood vaccination for HBV, with subsequent recommendations for vaccination of adolescents and adults in high-risk groups in 1995, and in 1999 all remaining unvaccinated children aged ≤ 19 years.9 Military policy has been to provide hepatitis B immunization to personnel assigned to the Korean peninsula since 1986 and to all recruits since 2001.10

Following publication of an Institute of Medicine/National Academies of Sciences, Engineering, and Medicine (NASEM) report, in 2011 the US Department of Health and Human Services (HHS) released the first National Viral Hepatitis Action Plan.11 The current HHS Action Plan, along with the NASEM National Strategy for the Elimination of Hepatitis B and C: Phase Two Report, commissioned by the US Centers for Disease Control and Prevention (CDC), outlines a national strategy to prevent new viral hepatitis infections; reduce deaths and improve the health of people living with viral hepatitis; reduce viral hepatitis health disparities; and coordinate, monitor, and report on implementation of viral hepatitis activities.12 The VA is a critical partner in this federal collaborative effort to achieve excellence in viral hepatitis care.

In August 2016, the HIV, Hepatitis, and Related Conditions Programs in the VA Office of Specialty Care Services convened a National Hepatitis B Working Group consisting of VA subject matter experts (SMEs) and representatives from the VA Central Office stakeholder program offices, with a charge of developing a strategic plan to ensure excellence in HBV prevention, care, and management across the VHA. The task included addressing supportive processes and barriers at each level of the organization through a public health framework and using a population health management approach.

The VA National Strategic Plan for Excellence in HBV Care was focused on the following overarching aims:

  • Characterizing the current state of care for veterans with HBV in VA care;
  • Developing and disseminating clinical guidance on high-quality care for patients with HBV;
  • Developing population data and informatics tools to streamline the identification and monitoring of patients with chronic HBV; and
  • Evaluating VHA care for patients with HBV over time.
 

 

Care for Veterans With HBV at the VA

The VA health care system is America’s largest integrated health care system, providing care at 1,243 health care facilities, including 170 medical centers and 1,063 outpatient sites of care serving 9 million enrolled veterans each year.13 As of January 2018, there were 10,743 individuals with serologic evidence for chronic HBV infection in VA care, based on a definition of 2 or more detectable surface antigen (sAg) or hepatitis B DNA tests recorded at least 6 months apart.1 About 2,000 additional VA patients have a history of a single positive sAg test. These patients have unclear HBV status and require a second sAg test to determine whether they have a chronic infection.

The prevalence of HBV infection among veterans in VA care is slightly higher than that in the US civilian population at 0.4%.14 Studies of selected subpopulations of veterans have found high seropositivity of prior or chronic HBV infection among homeless veterans and veterans admitted to a psychiatric hospital.15,16 The data from 2015 suggest that homeless veterans have a chronic HBV infection rate of 1.0%.14 Of those with known chronic HBV infection, the plurality are white (40.4%) or African American (40.2%), male (92.4%), with a mean age of 59.9 (SD 12.0) years. According to National HIV, Hepatitis and Related Conditions Data and Analysis Group personal correspondence, the geographic territories with the largest chronic HBV caseload include the Southeast, Gulf Coast, and West Coast. As of January 2018, 1,210 veterans in care have HBV-related cirrhosis.

HBV Screening in VA

The current VA HBV screening guidelines follow those of the US Preventive Services Task Force (USPSTF).17 HBV screening is recommended for unvaccinated individuals in high-risk groups, such as patients with HIV or hepatitis C virus (HCV), those on hemodialysis, those with elevated alanine transaminase/aspartate transaminase of unknown etiology, those on immunosuppressive therapy, injection drug users, the MSM population, people with household contact with an HBV-infected person, people born to an HBV-infected mother, those with risk factors for HBV exposure prior to vaccination, pregnant women, and people born in highly endemic areas regardless of vaccination status.2 The VHA recommends against standardized risk assessment and laboratory screening for HBV infection in the asymptomatic general patient population. However, if risk factors become known during the course of providing usual clinical care, then laboratory screening should be considered.2

Of the 6.1 million VHA users in fiscal year (FY) 2016, 26% have received HBV testing, an increase from 21.8% in FY 2013, despite enrollment of nearly 500,000 new VA users since that time. Screening rates for HBV among veterans in VHA care with HIV and HCV are > 94%.18 The VHA screening rates for HBV for veterans receiving immunosuppressive therapy, who inject drugs, or who have sexually transmitted infection are estimated to be 43.9%, 53.5%, and 51.4%, respectively.18 Testing for HBV sAg in homeless US veterans is estimated at 52.8% using data from a 2015 prevalence study.14

HBV Care and VA Antiviral Treatment

In a study of an HBV care cascade, Serper and colleagues reviewed a cohort of veterans in the VA with HBV. About 50% of the patients with known chronic HBV in the VA system from 1999 to 2013 had received infectious diseases or gastroenterology/hepatology specialty care in the previous 2 years.19 Follow-up data from the National HIV, Hepatitis and Related Conditions Data and Analysis Group indicated that this remains the case: 52.3% of patients with documented chronic HBV had received specialty care from VA sources in the prior 2 years. Serper and colleagues also reported that among veterans in VHA care with chronic HBV infection and cirrhosis from 1999 to 2013, annual imaging was < 50%, and initiation of antiviral treatment was only 39%. Antiviral therapy and liver imaging were both independently associated with lower mortality for patients with HBV and cirrhosis.19

A review of studies that evaluated the delivery of care for patients with HBV in U.S. civilian populations, including retrospective reviews of private payer claims databases and chart reviews, the Kaiser Permanente claims database, and community gastrointestinal (GI) practice chart reviews, revealed similar practice patterns with those in the VA.20 Across the US, rates of antiviral therapy and HCC surveillance for those with HBV cirrhosis were low, ranging from 14% to 50% and 19% to 60%, respectively. Several of these studies also found that being seen by an HBV specialist was associated with improved care.20

Antiviral treatment of individuals with cirrhosis and chronic HBV infection can reduce the risk of progression to decompensated cirrhosis and liver cancer. Among current VA patients with HBV cirrhosis, 62.4% received at least 1 month of HBV antiviral medication in the prior year. Additionally, biannual liver imaging is recommended in this population to screen for the development of HCC. According to National HIV, Hepatitis and Related Conditions Data and Analysis Group personal correspondence, nationally, 51.2% of individuals with HBV cirrhosis had received at least one instance of liver imaging within the past 6 months, and 71.2% received imaging within the past 12 months.

 

 

Prevention of HBV Infection and Sequelae

Vaccination rates in the US vary by age group, with higher immunization rates among those born after 1991 than the rates of those born earlier. Data from the National Health and Nutrition Examination Survey from 1988 to 2012 reported 33% immunity among veterans aged < 50 years and 6% among those aged ≥ 50 years.21 In addition to individuals who received childhood vaccination in the 1990s, all new military recruits assigned to the Korean Peninsula were vaccinated for HBV as of 1986, and those joining the military after 2002 received mandatory vaccination.

The VA follows the ACIP/CDC hepatitis B immunization guidelines.22-24 The VA currently recommends HBV immunization among previously unvaccinated adults at increased risk of contracting HBV infection and for any other adult who is seeking protection from HBV infection. The VA also offers general recommendations for prevention of transmission between veterans with known chronic HBV to their household, sexual, or drug-using partners. Transmission prevention guidelines also provide recommendations for vaccination of pregnant women with HBV risk factors and women at risk for HBV infection during pregnancy.22

HBV Care Guidance

One of the core tasks of the VA National Hepatitis B Working Group, given its broad, multidisciplinary expertise in HBV, was developing general clinical guidelines for the provision of high-quality care for patients with HBV. The group reviewed current literature and scientific evidence on care for patients with HBV. The working group relied heavily on the VA’s national guidelines for HBV screening and immunization, which are based on recommendations from the USPSTF, ACIP, CDC, and professional societies. The professional society guidelines included the American Association for the Study of Liver Disease’s Guidelines for Treatment of Chronic Hepatitis B, the America College of Gastroenterology’s Practice Guidelines: Evaluation of Abnormal Liver Chemistries, the American Gastroenterological Association Institute’s Guidelines for Prevention and Treatment of Hepatitis B Reactivation during Immunosuppressive Drug Therapy, and CDC’s Guidelines for Screening Pregnant Women for HBV.19,22-27

The working group identified areas for HBV quality improvement that were consistent with the VA and professional guidelines, specific and measurable using VA data, clinically relevant, feasible, and achievable in a defined time period. Areas for targeted improvement will include testing for HBV among high-risk patients, increasing antiviral treatment and HCC surveillance of veterans with HBV-related cirrhosis, decreasing progression of chronic HBV to cirrhosis, and expanding prevention measures, such as immunization among those at high risk for HBV and prevention of HBV reactivation.

At a national level, development of specific and measurable quality of care indicators for HBV will aid in assessing gaps in care and developing strategies to address these gaps. A broader discussion of care for patients with HBV quality with front-line health care providers (HCPs) will be paired with increased education and providing clinical support tools for those HCPs and facilities without access to specialty GI services.

Clinical pharmacists will be critical targets for the dissemination of guidance for HBV care paired with clinical informatics support tools and clinical educational opportunities. As of 2015, there were about 7,700 clinical pharmacists in the VHA and 3,200 had a scope of practice that included prescribing authority. As a result, 20% of HCV prescriptions in the VA in fiscal year 2015 were written by a clinical pharmacy specialist.28 Since then, the VA has expanded the education and support of clinical pharmacists in the care of patients with HCV and advanced liver disease, making them uniquely suited to provide additional support for a complex, low-prevalence disease like HBV.

Identification and Monitoring

The HBV working group and the VA Viral Hepatitis Technical Advisory Group are working with field HCPs to develop several informatics tools to promote HBV case identification and quality monitoring. These groups identified several barriers to HBV case identification and monitoring. The following informatics tools are either available or in development to reduce these barriers:

  1. A local clinical case registry of patients with HBV infection based on ICD codes, which allows users to create custom reports to identify, monitor, and track care;
  2. Because of the risk of HBV reactivation in patients with chronic HBV infection who receive anti-CD20 agents, such as rituximab, a medication order check to improve HBV screening among veterans receiving anti-CD20 medication;
  3. Validated patient reports based on laboratory diagnosis of HBV, drawn from all results across the VHA since 1999, made available to all facilities;
  4. Interactive reports summarizing quality of care for patients with HBV infection, based on facility-level indicators in development by the national HBV working group, will be distributed and enable geographic comparison;
  5. An HBV immunization clinical reminder that will prompt frontline HCPs to test and vaccinate; and
  6. An HBV clinical dashboard that will enable HCPs and facilities to identify all their HBV-positive veterans and track their care and outcomes over time.
 

 

Evaluating VA Care for Patients with HBV

As indicators of quality of HBV care are refined for VA patients and the health care delivery system, guidance will be made broadly available to frontline HCPs and administrators. The HBV quality of care recommendations will be paired with a suite of clinical informatics tools and virtual educational trainings to ensure that VA HCPs and facilities can streamline care for patients with HBV infection as much as possible. Quality improvement will be measured nationally each year, and strategies to address persistent variability and gaps in care will be developed in collaboration with the VA SME’s, facilities, and HCPs.

Conclusion

Hepatitis B virus is at least as prevalent among veterans who are cared for at VA facilities as it is in the US civilian population. Although care for patients with HBV infection in the VA is similar to care for patients with HBV infection in the community, the VA recognizes areas for improved HBV prevention, testing, care, and treatment. The VA has begun a continuous quality improvement strategic plan to enhance the level of care for patients with HBV infection in VA care. Centralized coordination and communication of VA data combined with veteran- and field-centered policies and operational planning and execution will allow clinically relevant improvements in HBV diagnosis, treatment, and prevention among veterans served by VA.

Click here to read the digital edition.

References

1. Centers for Disease Control and Prevention. Hepatitis B FAQs for health professionals: overview and statistics. https://www.cdc.gov/hepatitis/hbv/hbvfaq .htm#overview. Updated January 11, 2018. Accessed on February 12, 2018.

2. USDepartment of Veterans Affairs. National clinical preventive service guidance statements: hepatitis B screening. http://vaww.prevention.va.gov/CPS/Screen ing_for_Hepatitis_B.asp. Published August 11, 2016. [Nonpublic document; source not verified.]

3. Centers for Disease Control and Prevention. Surveillance for viral hepatitis—United States, 2015. https://www.cdc.gov/hepatitis/statistics/2015surveillance/index.htm. Updated June 19, 2017. Accessed February 12, 2018.

4. Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49(suppl 5):S28-S34.

5. Harris AM, Iqbal K, Schillie S, et al. Increases in acute hepatitis B virus infections— Kentucky, Tennessee, and West Virginia, 2006-2013. MMWR Morb Mortal Wkly Rep. 2016;65(3):47-50.

6. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373(9663):582-592.

7. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118-1127.

8. Weinbaum CM, Williams I, Mast EE, et al; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.

9. Centers for Disease Control and Prevention. Achievements in public health: hepatitis B vaccination—United States, 1982-2002. MMWR. 2002;51(25):549-552, 563.

10. Grabenstein JD, Pittman PR, Greenwood JT, Engler RJ. Immunization to protect the US Armed Forces: heritage, current practice, and prospects. Epidemiol Rev. 2006;28:3-26.

11. Colvin HM, Mitchell AE, eds; Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: National Academies Press; 2010.

12. National Academies of Sciences, Engineering, and Medicine. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report. Washington, DC: National Academies Press; 2017.

13. US Department of Veterans Affairs. Providing health care for veterans. https://www.va.gov/health. Updated February 20, 2018. Accessed February 22, 2018.

14. Noska AJ, Belperio PS, Loomis TP, O’Toole TP, Backus LI. Prevalence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus among homeless and nonhomeless United States veterans. Clin Infect Dis. 2017;65(2):252-258.

15. Gelberg L, Robertson MJ, Leake B, et al. Hepatitis B among homeless and other impoverished US military veterans in residential care in Los Angeles. Public Health. 2001;115(4):286-291.

16. Tabibian JH, Wirshing DA, Pierre JM, et al. Hepatitis B and C among veterans in a psychiatric ward. Dig Dis Sci. 2008;53(6):1693-1698

17. US Preventive Services Task Force. Final recommendation statement: screening for hepatitis B virus infection in nonpregnant adolescents and adults. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-b-virus-infection-screening-2014. Published May 2014. Updated February 2018. Accessed February 22, 2018.

18. Backus LI, Belperio PS, Loomis TP, Han SH, Mole LA. Screening for and prevalence of hepatitis B virus infection among high-risk veterans under the care of the U.S. Department of Veterans Affairs: a case report. Ann Intern Med. 2014;161(12):926-928.

19. Serper M, Choi G, Forde KA, Kaplan DE. Care delivery and outcomes among US veterans with hepatitis B: a national cohort study. Hepatology. 2016;63(6):1774-1782.

20. Mellinger J, Fontana RJ. Quality of care metrics in chronic hepatitis B. Hepatology. 2016;63(6):1755-1758.

21. Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63(2):388-397.

22. US Department of Veterans Affairs. National Clinical Preventive Service Guidance Statements: Hepatitis B Immunization. http://vaww.prevention.va.gov/CPS/Hepatitis_B_Immunization.asp. Nonpublic document. Source not verified.

23. Advisory Committee on Immunization Practices (ACIP). Recommended immunization schedule for adults aged 19 years or older, United States, 2017. https://www.cdc.gov/vaccines/schedules/hcp/adult.html. Accessed February 12, 2018.

24. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2018;67(1):1-31.

25. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283.

26. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.

27. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT; American Gastroenterological Association Institute. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215-219, quiz e16-e17.

28. Ourth H, Groppi J, Morreale AP, Quicci-Roberts K. Clinical pharmacist prescribing activities in the Veterans Health Administration. Am J Health Syst Pharm. 2016;73(18):1406-1415.

References

1. Centers for Disease Control and Prevention. Hepatitis B FAQs for health professionals: overview and statistics. https://www.cdc.gov/hepatitis/hbv/hbvfaq .htm#overview. Updated January 11, 2018. Accessed on February 12, 2018.

2. USDepartment of Veterans Affairs. National clinical preventive service guidance statements: hepatitis B screening. http://vaww.prevention.va.gov/CPS/Screen ing_for_Hepatitis_B.asp. Published August 11, 2016. [Nonpublic document; source not verified.]

3. Centers for Disease Control and Prevention. Surveillance for viral hepatitis—United States, 2015. https://www.cdc.gov/hepatitis/statistics/2015surveillance/index.htm. Updated June 19, 2017. Accessed February 12, 2018.

4. Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49(suppl 5):S28-S34.

5. Harris AM, Iqbal K, Schillie S, et al. Increases in acute hepatitis B virus infections— Kentucky, Tennessee, and West Virginia, 2006-2013. MMWR Morb Mortal Wkly Rep. 2016;65(3):47-50.

6. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373(9663):582-592.

7. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118-1127.

8. Weinbaum CM, Williams I, Mast EE, et al; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.

9. Centers for Disease Control and Prevention. Achievements in public health: hepatitis B vaccination—United States, 1982-2002. MMWR. 2002;51(25):549-552, 563.

10. Grabenstein JD, Pittman PR, Greenwood JT, Engler RJ. Immunization to protect the US Armed Forces: heritage, current practice, and prospects. Epidemiol Rev. 2006;28:3-26.

11. Colvin HM, Mitchell AE, eds; Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: National Academies Press; 2010.

12. National Academies of Sciences, Engineering, and Medicine. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report. Washington, DC: National Academies Press; 2017.

13. US Department of Veterans Affairs. Providing health care for veterans. https://www.va.gov/health. Updated February 20, 2018. Accessed February 22, 2018.

14. Noska AJ, Belperio PS, Loomis TP, O’Toole TP, Backus LI. Prevalence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus among homeless and nonhomeless United States veterans. Clin Infect Dis. 2017;65(2):252-258.

15. Gelberg L, Robertson MJ, Leake B, et al. Hepatitis B among homeless and other impoverished US military veterans in residential care in Los Angeles. Public Health. 2001;115(4):286-291.

16. Tabibian JH, Wirshing DA, Pierre JM, et al. Hepatitis B and C among veterans in a psychiatric ward. Dig Dis Sci. 2008;53(6):1693-1698

17. US Preventive Services Task Force. Final recommendation statement: screening for hepatitis B virus infection in nonpregnant adolescents and adults. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-b-virus-infection-screening-2014. Published May 2014. Updated February 2018. Accessed February 22, 2018.

18. Backus LI, Belperio PS, Loomis TP, Han SH, Mole LA. Screening for and prevalence of hepatitis B virus infection among high-risk veterans under the care of the U.S. Department of Veterans Affairs: a case report. Ann Intern Med. 2014;161(12):926-928.

19. Serper M, Choi G, Forde KA, Kaplan DE. Care delivery and outcomes among US veterans with hepatitis B: a national cohort study. Hepatology. 2016;63(6):1774-1782.

20. Mellinger J, Fontana RJ. Quality of care metrics in chronic hepatitis B. Hepatology. 2016;63(6):1755-1758.

21. Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63(2):388-397.

22. US Department of Veterans Affairs. National Clinical Preventive Service Guidance Statements: Hepatitis B Immunization. http://vaww.prevention.va.gov/CPS/Hepatitis_B_Immunization.asp. Nonpublic document. Source not verified.

23. Advisory Committee on Immunization Practices (ACIP). Recommended immunization schedule for adults aged 19 years or older, United States, 2017. https://www.cdc.gov/vaccines/schedules/hcp/adult.html. Accessed February 12, 2018.

24. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2018;67(1):1-31.

25. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283.

26. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.

27. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT; American Gastroenterological Association Institute. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215-219, quiz e16-e17.

28. Ourth H, Groppi J, Morreale AP, Quicci-Roberts K. Clinical pharmacist prescribing activities in the Veterans Health Administration. Am J Health Syst Pharm. 2016;73(18):1406-1415.

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Hepatitis A Virus Prevention and Vaccination Within and Outside the VHA in Light of Recent Outbreaks (FULL)

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Although widespread hepatitis A vaccination has dramatically decreased infection rates, a large proportion of VA patients in traditionally high-risk groups remains susceptible to infection.

Hepatitis A virus (HAV) can result in acute infection characterized by fatigue, nausea, jaundice (yellowing of the skin) and, rarely, acute liver failure and death.1,2 In the US, HAV yearly incidence (per 100,000) has decreased from 11.7 cases in 1996 to 0.4 cases in 2015, largely due to the 2006 recommendations from the Centers for Disease Control and Prevention (CDC) that all infants receive HAV vaccination.3,4

In 2017, multiple HAV outbreaks occurred in Arizona, California, Colorado, Kentucky, Michigan, and Utah with infections concentrated among those who were homeless, used illicit drugs (both injection and noninjection), or had close contact with these groups (Table 1).5-7 

These HAV outbreaks resulted in more than 1,000 hospitalizations and 45 reported deaths. The true scope of the outbreaks is believed to be much larger, given that HAV cases are under-reported.8

In response, the CDC has recommended the administration of HAV vaccine or immune globulin (IG) as postexposure prophylaxis (PEP) to people in high-risk groups including unvaccinated individuals exposed to HAV within the prior 2 weeks.5 While the Veterans Health Administration (VHA) in the Department of Veteran’s Affairs (VA) has not noted a significant increase in the number of reported HAV infections, there have been cases of hospitalization within the VA health care system due to HAV in at least 2 of the outbreak areas. The VA facilities in outbreak areas are responding by supporting county disease-control measures that include ensuring handwashing stations and vaccinations for high-risk, in-care populations and employees in direct contact with patients at high risk for HAV.

This review provides information on HAV transmission and clinical manifestations, guidelines on the prevention of HAV infection, and baseline data on current HAV susceptibility and immunization rates in the VHA.

Transmission and Clinical Manifestations

Hepatitis A virus is primarily transmitted by ingestion of small amounts of infected stool (ie, fecal-oral route) via direct person-to-person contact or through exposure to contaminated food or water.9,10 Groups at high risk of HAV infection include those in direct contact with HAV-infected individuals, users of injection or non-injection drugs, men who have sex with men (MSM), travelers to high-risk countries, individuals with clotting disorders, and those who work with nonhuman primates.11 Individuals who are homeless are susceptible to HAV due to poor sanitary conditions, and MSM are at increased risk of HAV acquisition via exposure to infected stool during sexual activity.

Complications of acute HAV infection, including fulminant liver failure and death, are more common among patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV).12,13 While infection with HIV does not independently increase the risk of HAV acquisition, about 75% of new HIV infections in the US are among MSM or IV drug users who are at increased risk of HAV infection.14 In addition, duration of HAV viremia and resulting HAV transmissibility may be increased in HIV-infected individuals.15-17

After infection, HAV remains asymptomatic (the incubation period) for an average of 28 days with a range of 15 to 50 days.18,19 Most children younger than 6 years remain asymptomatic while older children and adults typically experience symptoms including fever, fatigue, poor appetite, abdominal pain, dark urine, clay-colored stools, and jaundice.2,20,21 Symptoms typically last less than 2 months but can persist or relapse for up to 6 months in 10% to 15% of symptomatic individuals.22,23 Those with HAV infection are capable of viral transmission from the beginning of the incubation period until about a week after jaundice appears.24 Unlike HBV and HCV, HAV does not cause chronic infection.

Fulminant liver failure, characterized by encephalopathy, jaundice, and elevated international normalized ratio (INR), occurs in < 1% of HAV infections and is more common in those with underlying liver disease and older individuals.13,25-27 In one retrospective review of fulminant liver failure from HAV infection, about half of the patients required liver transplantation or died within 3 weeks of presentation.12

Other than supportive care, there are no specific treatments for acute HAV infection. However, the CDC recommends that healthy individuals aged between 1 and 40 years with known or suspected exposure to HAV within the prior 2 weeks receive 1 dose of a single-antigen HAV vaccination. The CDC also recommends that recently exposed individuals aged < 1 year or > 40 years, or patients who are immunocompromised, have chronic liver disease (CLD), or are allergic to HAV vaccine or a vaccine component should receive a single IG injection. In addition, the CDC recommends that health care providers report all cases of acute HAV to state and local health departments.28

In patients with typical symptoms of acute viral hepatitis (eg, headache, fever, malaise, anorexia, nausea, vomiting, abdominal pain, and diarrhea) and either jaundice or elevated serum aminotransferase levels, confirmation of HAV infection is required with either a positive serologic test for immunoglobulin M (IgM) anti-HAV antibody or an epidemiologic link (eg, recent household or close contact) to a person with laboratory-confirmed HAV.5 Serum IgM anti-HAV antibodies are first detectable when symptoms begin and remain detectable for about 3 to 6 months.29,30 Serum immunoglobulin G (IgG) anti-HAV antibodies, which provide lifelong protection against reinfection, appear as symptoms improve and persist indefinitely.31,32 Therefore, the presence of anti-HAV IgG and the absence of anti-HAV IgM is indicative of immunity to HAV via past infection or vaccination.

 

 

HAV Prevention in The VHA

The mainstay of HAV prevention is vaccination with 2 doses of inactivated, single-antigen hepatitis A vaccine or 3 doses of combination (HAV and HBV) vaccine.11 Both single antigen and combination HAV vaccines are safe in immunocompromised and pregnant patients.33-39 The HAV vaccination results in 100% anti-HAV IgG seropositivity among healthy individuals, although immunogenicity might be lower for those who are immunocompromised or with CLD.31,40-47 The VHA recommends HAV immunization, unless contraindicated, for previously unvaccinated 

adults who are at increased risk of contracting HAV and for any other adult who is seeking protection from HAV infection (Table 2).48 Hepatitis A virus vaccination is not specifically recommended for workers in food service, health care, sanitation, or child care.11

In addition to vaccination, addressing risk factors for HAV infection and its complications could reduce the burden of disease. For instance, recent outbreaks highlight that homeless individuals and users of injection and noninjection drugs are particularly vulnerable to infections transmitted via fecal-oral contamination. Broad strategies to address homelessness and related sanitation concerns are needed to help reduce the likelihood of future HAV outbreaks.49 Specific measures to combat HAV include providing access to clean water, adequate hygiene, and clean needles for people who inject drugs.11 Hepatitis A virus can be destroyed by heating food to ≥ 185 °F for at least 1 minute, chlorinating contaminated water, or cleaning contaminated surfaces with a solution of household bleach and water.50 Moreover, it is important to identify and treat risk factors for complications of HAV infection. This includes identifying individuals with HCV and ensuring that they are immune to HAV, given data that HCV-infected individuals are at increased risk of fulminant hepatic failure from HAV.12,13

Active-duty service members have long been considered at higher risk of HAV infections due to deployments in endemic areas and exposure to contaminated food and water.51,52 Shortly after the FDA approved HAV vaccination in 1995, the Department of Defense (DoD) mandated screening and HAV immunization for all incoming active-duty service members and those deployed to areas of high endemicity.53 However, US veterans who were discharged before the adoption of universal HAV vaccination remain at increased risk for HAV infection, particularly given the high prevalence of CLD, homelessness, and substance use disorder (SUD) in this cohort.54-56 Given the importance of HAV prevention for high-risk individuals, an analysis was performed to determine rates of HAV vaccination and testing within VA-enrolled individuals with selected risk factors for HAV acquisition or complications.

Methods

A cross-sectional analysis of veterans in VA care from June 1, 2016 to June 1, 2017 was performed to determine national rates of HAV susceptibility among patients with HCV exposure, homelessness, SUD, or HIV infection. The definitions of homelessness, SUD (alcohol, cannabis, opioid, sedatives, hallucinogens, inhalants, stimulants, or tobacco), and HIV infection were based on the presence of appropriate ICD-9 or ICD-10 codes. History of HCV exposure was based on a positive HCV antibody test. Presence of HAV vaccination was determined based on CPT codes for administration of the single-antigen HAV vaccination or combination HAV/HBV vaccination.

While HIV infection is not independently considered an indication for HAV vaccination, the authors included this group given its high proportion of patients with other risk factors, including MSM and IV drug use. All data were obtained from the VA Corporate Data Warehouse (CDW), a comprehensive national repository of all laboratory, diagnosis, and prescription results (including vaccines) within the VHA since 1999.

Hepatitis A virus nonsusceptibility was defined as (1) documented receipt of HAV vaccination within the VHA; (2) anti-HAV IgG antibody testing within the VHA; or (3) active-duty service after October 1997. It was considered likely that patients who received HAV testing either showed evidence of HAV immunity (eg, positive anti-HAV IgG) or were anti-HAV IgG negative and subsequently immunized. Therefore, patients with anti-HAV IgG antibody testing were counted presumptively as nonsusceptible. The DoD implemented a universal HAV vaccination policy in 1995, therefore, 1997 was chosen as a time at which the military’s universal HAV vaccination campaign was likely to have achieved near 100% vaccination coverage of active-duty military.

 

Results

The cohort included 5,896,451 patients in VA care, including 381,628 (6.5%) who were homeless, 455,344 (7.7%) with SUD, 225,889 (3.8%) with a lifetime history of positive HCV antibody (indicating past HCV exposure), and 29,166 (0.5%) with HIV infection.

National rates of HAV susceptibility were lowest among patients with HIV (mean 21.8%, facility range 0%-56.5%) followed by SUD (mean 47.4%, facility range 3.8%-70.4%), homelessness (mean 48.4%, facility range 5.9%-69.3%), and HCV exposure (mean 48.9%, facility range 30.5%-71.6%) (Table 3).

 

 

There was wide geographic variability in rates of HAV susceptibility (Figure 1). 

When limiting the analysis to patients with confirmed vaccination within the VHA or active duty military service after October 1997, VA facilities in states with active outbreaks had a mean HAV vaccination rate of 38.1% (range 31.5%-44.3%) among patients who were homeless and 42.0% (range 33.8%-49.0%) among patients with SUD.

Discussion

Widespread HAV vaccination has decreased the incidence of HAV infection in the US dramatically. Nevertheless, recent outbreaks demonstrate that substantial population susceptibility and associated risk for HAV-related morbidity and mortality remains, particularly in high-risk populations. Although the VHA has not experienced a significant increase in acute HAV infections to date, this cross-sectional analysis highlights that a large proportion of VA patients in traditionally high-risk groups remain susceptible to HAV infection.

Strengths

Strengths of this analysis include a current reflection of HAV susceptibility within the national VHA, thus informing HAV testing and vaccination strategies. This study also involves a very large cohort, which is possible because the VHA is the largest integrated healthcare system in the US. Lastly, because the VHA uses electronic medical records, there was nearly complete capture of HAV vaccinations and testing obtained through the VHA.

Limitations

This cross-sectional analysis has several potential limitations. First, findings may not be generalizable outside the VHA. In addition, determination of homelessness, substance abuse, and HIV infection were based on ICD-9 and ICD-10 codes, which have been used in previous studies but may be subject to misclassification. The authors deliberately included all patients with positive HCV antibody testing to include those with current or prior risk factors for HAV acquisition. This population does not reflect patients with HCV viremia who received HAV testing or vaccination. Lastly, misattribution of HAV susceptibility could have occurred if patients with negative HAV IgG results were not vaccinated or if patients previously received HAV vaccination outside the VHA.

Conclusion

To mitigate the risk of future HAV outbreaks, continued efforts should be made to increase vaccination among high-risk groups, improve awareness of additional prevention measures, and address risk factors for HAV acquisition, particularly in areas with active outbreaks. Further study is suggested to identify geographic areas with large caseloads of at-risk patients and to highlight best practices utilized by VHA facilities that achieved high vaccine coverage rates. Recommended approaches likely will need to include efforts to improve hygiene and reduce risks for HAV exposure associated with SUD and homelessness.

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31. Plumb ID, Bulkow LR, Bruce MG, et al. Persistence of antibody to Hepatitis A virus 20 years after receipt of Hepatitis A vaccine in Alaska. J Viral Hepat. 2017;24(7):608-612.

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34. Ambrosch F, André FE, Delem A, et al. Simultaneous vaccination against hepatitis A and B: results of a controlled study. Vaccine. 1992;10(suppl 1):S142-S145.

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36. Jong EC, Kaplan KM, Eves KA, Taddeo CA, Lakkis HD, Kuter BJ. An open randomized study of inactivated hepatitis A vaccine administered concomitantly with typhoid fever and yellow fever vaccines. J Travel Med. 2002;9(2):66-70.

37. Nolan T, Bernstein H, Blatter MM, et al. Immunogenicity and safety of an inactivated hepatitis A vaccine administered concomitantly with diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines to children less than 2 years of age. Pediatrics. 2006;118(3):e602-e609.

38. Usonis V, Meriste S, Bakasenas V, et al. Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months. Vaccine. 2005;23(20):2602-2606.

39. Moro PL, Museru OI, Niu M, Lewis P, Broder K. Reports to the Vaccine Adverse Event Reporting System after hepatitis A and hepatitis AB vaccines in pregnant women. Am J Obstet Gynecol. 2014;210(6):561.e1-561.e-6.

40. André FE, D’Hondt E, Delem A, Safary A. Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. Vaccine. 1992;10(suppl 1):S160-S168.

41. Just M, Berger R. Reactogenicity and immunogenicity of inactivated hepatitis A vaccines. Vaccine. 1992;10(suppl 1):S110-S113.

42. McMahon BJ, Williams J, Bulkow L, et al. Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and Native and non-Native adults. J Infect Dis. 1995;171(3):676-679.

43. Balcarek KB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis. 1995;171(suppl 1):S70-S72.

44. Bell BP, Negus S, Fiore AE, et al. Immunogenicity of an inactivated hepatitis A vaccine in infants and young children. Pediatr Infect Dis J. 2007;26(2):116-122.

45. Arguedas MR, Johnson A, Eloubeidi MA, Fallon MB. Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients. Hepatology. 2001;34(1):28-31.

46. Overton ET, Nurutdinova D, Sungkanuparph S, Seyfried W, Groger RK, Powderly WG. Predictors of immunity after hepatitis A vaccination in HIV-infected persons. J Viral Hepat. 2007;14(3):189-193.

47. Askling HH, Rombo L, van Vollenhoven R, et al. Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study. Travel Med Infect Dis. 2014;12(2):134-142.

48. US Department of Veterans Affairs. VHA national hepatitis A immunization guidelines. http://vaww.prevention.va.gov/CPS/Hepatitis_A_Immunization.asp. Nonpublic document. Source not verified.

49. Kushel M. Hepatitis A outbreak in California - addressing the root cause. N Engl J Med. 2018;378(3):211-213.

50. Millard J, Appleton H, Parry JV. Studies on heat inactivation of hepatitis A virus with special reference to shellfish. Part 1. Procedures for infection and recovery of virus from laboratory-maintained cockles. Epidemiol Infect. 1987;98(3):397-414.

51. Hoke CH, Jr., Binn LN, Egan JE, et al. Hepatitis A in the US Army: epidemiology and vaccine development. Vaccine. 1992;10(suppl 1):S75-S79.

52. Dooley DP. History of U.S. military contributions to the study of viral hepatitis. Mil Med. 2005;170(suppl 4):71-76.

53. Grabenstein JD, Pittman PR, Greenwood JT, Engler RJ. Immunization to protect the US Armed Forces: heritage, current practice, and prospects. Epidemiol Rev. 2006;28:3-26.

54. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013. Gastroenterology. 2015;149(6):1471-1482.e1475; quiz e17-e18.

55. Fargo J, Metraux S, Byrne T, et al. Prevalence and risk of homelessness among US veterans. Prev Chronic Dis. 2012;9:E45.

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Author and Disclosure Information

Dr. Moon is a Fellow in the Division of Gastroenterology and Hepatology at University of North Carolina School of Medicine in Chapel Hill, North Carolina. Dr. Lowy is a Data Analyst for the HHRC Data and Analytics Group and Data Analyst for Health Services Research and Development at VA Puget Sound Healthcare System. Dr. Chartier is the Deputy Director and the National Infectious Diseases Officer for the Veterans Health Administration (VHA), Office of Specialty Care Services, HIV, Hepatitis, and Related Conditions Programs (HHRC). Dr. Beste is a Staff Physician and the Director of the VA National Liver Disease Database at VA Puget Sound Healthcare System, the Director of the HHRC Data Analytics Group, and Assistant Professor of Medicine in the Division of General Internal Medicine at the University of Washington in Seattle. Dr. Maier is a Staff Physician in the Infectious Diseases Section at VA Portland Healthcare System in Oregon and an Assistant Professor in the Division of Infectious Diseases at Oregon Health and Sciences University in Portland. Dr. Maier is the National Public Health Infectious Disease Officer. Dr. Morgan is the Director of the HHRC National Hepatitis Resource Center; Chief, Gastroenterology at VA Long Beach Healthcare System in California; and Professor in the Division of Gastroenterology at University of California, Irvine. Ms. Hoffman-Högg is National Program Manager for Prevention Policy at VHA National Center for Health Promotion and Disease Prevention in Durham, North Carolina
Correspondence: Dr. Moon (andrew.moon@unchealth.unc.edu)

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The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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Dr. Moon is a Fellow in the Division of Gastroenterology and Hepatology at University of North Carolina School of Medicine in Chapel Hill, North Carolina. Dr. Lowy is a Data Analyst for the HHRC Data and Analytics Group and Data Analyst for Health Services Research and Development at VA Puget Sound Healthcare System. Dr. Chartier is the Deputy Director and the National Infectious Diseases Officer for the Veterans Health Administration (VHA), Office of Specialty Care Services, HIV, Hepatitis, and Related Conditions Programs (HHRC). Dr. Beste is a Staff Physician and the Director of the VA National Liver Disease Database at VA Puget Sound Healthcare System, the Director of the HHRC Data Analytics Group, and Assistant Professor of Medicine in the Division of General Internal Medicine at the University of Washington in Seattle. Dr. Maier is a Staff Physician in the Infectious Diseases Section at VA Portland Healthcare System in Oregon and an Assistant Professor in the Division of Infectious Diseases at Oregon Health and Sciences University in Portland. Dr. Maier is the National Public Health Infectious Disease Officer. Dr. Morgan is the Director of the HHRC National Hepatitis Resource Center; Chief, Gastroenterology at VA Long Beach Healthcare System in California; and Professor in the Division of Gastroenterology at University of California, Irvine. Ms. Hoffman-Högg is National Program Manager for Prevention Policy at VHA National Center for Health Promotion and Disease Prevention in Durham, North Carolina
Correspondence: Dr. Moon (andrew.moon@unchealth.unc.edu)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Author and Disclosure Information

Dr. Moon is a Fellow in the Division of Gastroenterology and Hepatology at University of North Carolina School of Medicine in Chapel Hill, North Carolina. Dr. Lowy is a Data Analyst for the HHRC Data and Analytics Group and Data Analyst for Health Services Research and Development at VA Puget Sound Healthcare System. Dr. Chartier is the Deputy Director and the National Infectious Diseases Officer for the Veterans Health Administration (VHA), Office of Specialty Care Services, HIV, Hepatitis, and Related Conditions Programs (HHRC). Dr. Beste is a Staff Physician and the Director of the VA National Liver Disease Database at VA Puget Sound Healthcare System, the Director of the HHRC Data Analytics Group, and Assistant Professor of Medicine in the Division of General Internal Medicine at the University of Washington in Seattle. Dr. Maier is a Staff Physician in the Infectious Diseases Section at VA Portland Healthcare System in Oregon and an Assistant Professor in the Division of Infectious Diseases at Oregon Health and Sciences University in Portland. Dr. Maier is the National Public Health Infectious Disease Officer. Dr. Morgan is the Director of the HHRC National Hepatitis Resource Center; Chief, Gastroenterology at VA Long Beach Healthcare System in California; and Professor in the Division of Gastroenterology at University of California, Irvine. Ms. Hoffman-Högg is National Program Manager for Prevention Policy at VHA National Center for Health Promotion and Disease Prevention in Durham, North Carolina
Correspondence: Dr. Moon (andrew.moon@unchealth.unc.edu)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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Although widespread hepatitis A vaccination has dramatically decreased infection rates, a large proportion of VA patients in traditionally high-risk groups remains susceptible to infection.
Although widespread hepatitis A vaccination has dramatically decreased infection rates, a large proportion of VA patients in traditionally high-risk groups remains susceptible to infection.

Hepatitis A virus (HAV) can result in acute infection characterized by fatigue, nausea, jaundice (yellowing of the skin) and, rarely, acute liver failure and death.1,2 In the US, HAV yearly incidence (per 100,000) has decreased from 11.7 cases in 1996 to 0.4 cases in 2015, largely due to the 2006 recommendations from the Centers for Disease Control and Prevention (CDC) that all infants receive HAV vaccination.3,4

In 2017, multiple HAV outbreaks occurred in Arizona, California, Colorado, Kentucky, Michigan, and Utah with infections concentrated among those who were homeless, used illicit drugs (both injection and noninjection), or had close contact with these groups (Table 1).5-7 

These HAV outbreaks resulted in more than 1,000 hospitalizations and 45 reported deaths. The true scope of the outbreaks is believed to be much larger, given that HAV cases are under-reported.8

In response, the CDC has recommended the administration of HAV vaccine or immune globulin (IG) as postexposure prophylaxis (PEP) to people in high-risk groups including unvaccinated individuals exposed to HAV within the prior 2 weeks.5 While the Veterans Health Administration (VHA) in the Department of Veteran’s Affairs (VA) has not noted a significant increase in the number of reported HAV infections, there have been cases of hospitalization within the VA health care system due to HAV in at least 2 of the outbreak areas. The VA facilities in outbreak areas are responding by supporting county disease-control measures that include ensuring handwashing stations and vaccinations for high-risk, in-care populations and employees in direct contact with patients at high risk for HAV.

This review provides information on HAV transmission and clinical manifestations, guidelines on the prevention of HAV infection, and baseline data on current HAV susceptibility and immunization rates in the VHA.

Transmission and Clinical Manifestations

Hepatitis A virus is primarily transmitted by ingestion of small amounts of infected stool (ie, fecal-oral route) via direct person-to-person contact or through exposure to contaminated food or water.9,10 Groups at high risk of HAV infection include those in direct contact with HAV-infected individuals, users of injection or non-injection drugs, men who have sex with men (MSM), travelers to high-risk countries, individuals with clotting disorders, and those who work with nonhuman primates.11 Individuals who are homeless are susceptible to HAV due to poor sanitary conditions, and MSM are at increased risk of HAV acquisition via exposure to infected stool during sexual activity.

Complications of acute HAV infection, including fulminant liver failure and death, are more common among patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV).12,13 While infection with HIV does not independently increase the risk of HAV acquisition, about 75% of new HIV infections in the US are among MSM or IV drug users who are at increased risk of HAV infection.14 In addition, duration of HAV viremia and resulting HAV transmissibility may be increased in HIV-infected individuals.15-17

After infection, HAV remains asymptomatic (the incubation period) for an average of 28 days with a range of 15 to 50 days.18,19 Most children younger than 6 years remain asymptomatic while older children and adults typically experience symptoms including fever, fatigue, poor appetite, abdominal pain, dark urine, clay-colored stools, and jaundice.2,20,21 Symptoms typically last less than 2 months but can persist or relapse for up to 6 months in 10% to 15% of symptomatic individuals.22,23 Those with HAV infection are capable of viral transmission from the beginning of the incubation period until about a week after jaundice appears.24 Unlike HBV and HCV, HAV does not cause chronic infection.

Fulminant liver failure, characterized by encephalopathy, jaundice, and elevated international normalized ratio (INR), occurs in < 1% of HAV infections and is more common in those with underlying liver disease and older individuals.13,25-27 In one retrospective review of fulminant liver failure from HAV infection, about half of the patients required liver transplantation or died within 3 weeks of presentation.12

Other than supportive care, there are no specific treatments for acute HAV infection. However, the CDC recommends that healthy individuals aged between 1 and 40 years with known or suspected exposure to HAV within the prior 2 weeks receive 1 dose of a single-antigen HAV vaccination. The CDC also recommends that recently exposed individuals aged < 1 year or > 40 years, or patients who are immunocompromised, have chronic liver disease (CLD), or are allergic to HAV vaccine or a vaccine component should receive a single IG injection. In addition, the CDC recommends that health care providers report all cases of acute HAV to state and local health departments.28

In patients with typical symptoms of acute viral hepatitis (eg, headache, fever, malaise, anorexia, nausea, vomiting, abdominal pain, and diarrhea) and either jaundice or elevated serum aminotransferase levels, confirmation of HAV infection is required with either a positive serologic test for immunoglobulin M (IgM) anti-HAV antibody or an epidemiologic link (eg, recent household or close contact) to a person with laboratory-confirmed HAV.5 Serum IgM anti-HAV antibodies are first detectable when symptoms begin and remain detectable for about 3 to 6 months.29,30 Serum immunoglobulin G (IgG) anti-HAV antibodies, which provide lifelong protection against reinfection, appear as symptoms improve and persist indefinitely.31,32 Therefore, the presence of anti-HAV IgG and the absence of anti-HAV IgM is indicative of immunity to HAV via past infection or vaccination.

 

 

HAV Prevention in The VHA

The mainstay of HAV prevention is vaccination with 2 doses of inactivated, single-antigen hepatitis A vaccine or 3 doses of combination (HAV and HBV) vaccine.11 Both single antigen and combination HAV vaccines are safe in immunocompromised and pregnant patients.33-39 The HAV vaccination results in 100% anti-HAV IgG seropositivity among healthy individuals, although immunogenicity might be lower for those who are immunocompromised or with CLD.31,40-47 The VHA recommends HAV immunization, unless contraindicated, for previously unvaccinated 

adults who are at increased risk of contracting HAV and for any other adult who is seeking protection from HAV infection (Table 2).48 Hepatitis A virus vaccination is not specifically recommended for workers in food service, health care, sanitation, or child care.11

In addition to vaccination, addressing risk factors for HAV infection and its complications could reduce the burden of disease. For instance, recent outbreaks highlight that homeless individuals and users of injection and noninjection drugs are particularly vulnerable to infections transmitted via fecal-oral contamination. Broad strategies to address homelessness and related sanitation concerns are needed to help reduce the likelihood of future HAV outbreaks.49 Specific measures to combat HAV include providing access to clean water, adequate hygiene, and clean needles for people who inject drugs.11 Hepatitis A virus can be destroyed by heating food to ≥ 185 °F for at least 1 minute, chlorinating contaminated water, or cleaning contaminated surfaces with a solution of household bleach and water.50 Moreover, it is important to identify and treat risk factors for complications of HAV infection. This includes identifying individuals with HCV and ensuring that they are immune to HAV, given data that HCV-infected individuals are at increased risk of fulminant hepatic failure from HAV.12,13

Active-duty service members have long been considered at higher risk of HAV infections due to deployments in endemic areas and exposure to contaminated food and water.51,52 Shortly after the FDA approved HAV vaccination in 1995, the Department of Defense (DoD) mandated screening and HAV immunization for all incoming active-duty service members and those deployed to areas of high endemicity.53 However, US veterans who were discharged before the adoption of universal HAV vaccination remain at increased risk for HAV infection, particularly given the high prevalence of CLD, homelessness, and substance use disorder (SUD) in this cohort.54-56 Given the importance of HAV prevention for high-risk individuals, an analysis was performed to determine rates of HAV vaccination and testing within VA-enrolled individuals with selected risk factors for HAV acquisition or complications.

Methods

A cross-sectional analysis of veterans in VA care from June 1, 2016 to June 1, 2017 was performed to determine national rates of HAV susceptibility among patients with HCV exposure, homelessness, SUD, or HIV infection. The definitions of homelessness, SUD (alcohol, cannabis, opioid, sedatives, hallucinogens, inhalants, stimulants, or tobacco), and HIV infection were based on the presence of appropriate ICD-9 or ICD-10 codes. History of HCV exposure was based on a positive HCV antibody test. Presence of HAV vaccination was determined based on CPT codes for administration of the single-antigen HAV vaccination or combination HAV/HBV vaccination.

While HIV infection is not independently considered an indication for HAV vaccination, the authors included this group given its high proportion of patients with other risk factors, including MSM and IV drug use. All data were obtained from the VA Corporate Data Warehouse (CDW), a comprehensive national repository of all laboratory, diagnosis, and prescription results (including vaccines) within the VHA since 1999.

Hepatitis A virus nonsusceptibility was defined as (1) documented receipt of HAV vaccination within the VHA; (2) anti-HAV IgG antibody testing within the VHA; or (3) active-duty service after October 1997. It was considered likely that patients who received HAV testing either showed evidence of HAV immunity (eg, positive anti-HAV IgG) or were anti-HAV IgG negative and subsequently immunized. Therefore, patients with anti-HAV IgG antibody testing were counted presumptively as nonsusceptible. The DoD implemented a universal HAV vaccination policy in 1995, therefore, 1997 was chosen as a time at which the military’s universal HAV vaccination campaign was likely to have achieved near 100% vaccination coverage of active-duty military.

 

Results

The cohort included 5,896,451 patients in VA care, including 381,628 (6.5%) who were homeless, 455,344 (7.7%) with SUD, 225,889 (3.8%) with a lifetime history of positive HCV antibody (indicating past HCV exposure), and 29,166 (0.5%) with HIV infection.

National rates of HAV susceptibility were lowest among patients with HIV (mean 21.8%, facility range 0%-56.5%) followed by SUD (mean 47.4%, facility range 3.8%-70.4%), homelessness (mean 48.4%, facility range 5.9%-69.3%), and HCV exposure (mean 48.9%, facility range 30.5%-71.6%) (Table 3).

 

 

There was wide geographic variability in rates of HAV susceptibility (Figure 1). 

When limiting the analysis to patients with confirmed vaccination within the VHA or active duty military service after October 1997, VA facilities in states with active outbreaks had a mean HAV vaccination rate of 38.1% (range 31.5%-44.3%) among patients who were homeless and 42.0% (range 33.8%-49.0%) among patients with SUD.

Discussion

Widespread HAV vaccination has decreased the incidence of HAV infection in the US dramatically. Nevertheless, recent outbreaks demonstrate that substantial population susceptibility and associated risk for HAV-related morbidity and mortality remains, particularly in high-risk populations. Although the VHA has not experienced a significant increase in acute HAV infections to date, this cross-sectional analysis highlights that a large proportion of VA patients in traditionally high-risk groups remain susceptible to HAV infection.

Strengths

Strengths of this analysis include a current reflection of HAV susceptibility within the national VHA, thus informing HAV testing and vaccination strategies. This study also involves a very large cohort, which is possible because the VHA is the largest integrated healthcare system in the US. Lastly, because the VHA uses electronic medical records, there was nearly complete capture of HAV vaccinations and testing obtained through the VHA.

Limitations

This cross-sectional analysis has several potential limitations. First, findings may not be generalizable outside the VHA. In addition, determination of homelessness, substance abuse, and HIV infection were based on ICD-9 and ICD-10 codes, which have been used in previous studies but may be subject to misclassification. The authors deliberately included all patients with positive HCV antibody testing to include those with current or prior risk factors for HAV acquisition. This population does not reflect patients with HCV viremia who received HAV testing or vaccination. Lastly, misattribution of HAV susceptibility could have occurred if patients with negative HAV IgG results were not vaccinated or if patients previously received HAV vaccination outside the VHA.

Conclusion

To mitigate the risk of future HAV outbreaks, continued efforts should be made to increase vaccination among high-risk groups, improve awareness of additional prevention measures, and address risk factors for HAV acquisition, particularly in areas with active outbreaks. Further study is suggested to identify geographic areas with large caseloads of at-risk patients and to highlight best practices utilized by VHA facilities that achieved high vaccine coverage rates. Recommended approaches likely will need to include efforts to improve hygiene and reduce risks for HAV exposure associated with SUD and homelessness.

Click here to read the digital edition.

Hepatitis A virus (HAV) can result in acute infection characterized by fatigue, nausea, jaundice (yellowing of the skin) and, rarely, acute liver failure and death.1,2 In the US, HAV yearly incidence (per 100,000) has decreased from 11.7 cases in 1996 to 0.4 cases in 2015, largely due to the 2006 recommendations from the Centers for Disease Control and Prevention (CDC) that all infants receive HAV vaccination.3,4

In 2017, multiple HAV outbreaks occurred in Arizona, California, Colorado, Kentucky, Michigan, and Utah with infections concentrated among those who were homeless, used illicit drugs (both injection and noninjection), or had close contact with these groups (Table 1).5-7 

These HAV outbreaks resulted in more than 1,000 hospitalizations and 45 reported deaths. The true scope of the outbreaks is believed to be much larger, given that HAV cases are under-reported.8

In response, the CDC has recommended the administration of HAV vaccine or immune globulin (IG) as postexposure prophylaxis (PEP) to people in high-risk groups including unvaccinated individuals exposed to HAV within the prior 2 weeks.5 While the Veterans Health Administration (VHA) in the Department of Veteran’s Affairs (VA) has not noted a significant increase in the number of reported HAV infections, there have been cases of hospitalization within the VA health care system due to HAV in at least 2 of the outbreak areas. The VA facilities in outbreak areas are responding by supporting county disease-control measures that include ensuring handwashing stations and vaccinations for high-risk, in-care populations and employees in direct contact with patients at high risk for HAV.

This review provides information on HAV transmission and clinical manifestations, guidelines on the prevention of HAV infection, and baseline data on current HAV susceptibility and immunization rates in the VHA.

Transmission and Clinical Manifestations

Hepatitis A virus is primarily transmitted by ingestion of small amounts of infected stool (ie, fecal-oral route) via direct person-to-person contact or through exposure to contaminated food or water.9,10 Groups at high risk of HAV infection include those in direct contact with HAV-infected individuals, users of injection or non-injection drugs, men who have sex with men (MSM), travelers to high-risk countries, individuals with clotting disorders, and those who work with nonhuman primates.11 Individuals who are homeless are susceptible to HAV due to poor sanitary conditions, and MSM are at increased risk of HAV acquisition via exposure to infected stool during sexual activity.

Complications of acute HAV infection, including fulminant liver failure and death, are more common among patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV).12,13 While infection with HIV does not independently increase the risk of HAV acquisition, about 75% of new HIV infections in the US are among MSM or IV drug users who are at increased risk of HAV infection.14 In addition, duration of HAV viremia and resulting HAV transmissibility may be increased in HIV-infected individuals.15-17

After infection, HAV remains asymptomatic (the incubation period) for an average of 28 days with a range of 15 to 50 days.18,19 Most children younger than 6 years remain asymptomatic while older children and adults typically experience symptoms including fever, fatigue, poor appetite, abdominal pain, dark urine, clay-colored stools, and jaundice.2,20,21 Symptoms typically last less than 2 months but can persist or relapse for up to 6 months in 10% to 15% of symptomatic individuals.22,23 Those with HAV infection are capable of viral transmission from the beginning of the incubation period until about a week after jaundice appears.24 Unlike HBV and HCV, HAV does not cause chronic infection.

Fulminant liver failure, characterized by encephalopathy, jaundice, and elevated international normalized ratio (INR), occurs in < 1% of HAV infections and is more common in those with underlying liver disease and older individuals.13,25-27 In one retrospective review of fulminant liver failure from HAV infection, about half of the patients required liver transplantation or died within 3 weeks of presentation.12

Other than supportive care, there are no specific treatments for acute HAV infection. However, the CDC recommends that healthy individuals aged between 1 and 40 years with known or suspected exposure to HAV within the prior 2 weeks receive 1 dose of a single-antigen HAV vaccination. The CDC also recommends that recently exposed individuals aged < 1 year or > 40 years, or patients who are immunocompromised, have chronic liver disease (CLD), or are allergic to HAV vaccine or a vaccine component should receive a single IG injection. In addition, the CDC recommends that health care providers report all cases of acute HAV to state and local health departments.28

In patients with typical symptoms of acute viral hepatitis (eg, headache, fever, malaise, anorexia, nausea, vomiting, abdominal pain, and diarrhea) and either jaundice or elevated serum aminotransferase levels, confirmation of HAV infection is required with either a positive serologic test for immunoglobulin M (IgM) anti-HAV antibody or an epidemiologic link (eg, recent household or close contact) to a person with laboratory-confirmed HAV.5 Serum IgM anti-HAV antibodies are first detectable when symptoms begin and remain detectable for about 3 to 6 months.29,30 Serum immunoglobulin G (IgG) anti-HAV antibodies, which provide lifelong protection against reinfection, appear as symptoms improve and persist indefinitely.31,32 Therefore, the presence of anti-HAV IgG and the absence of anti-HAV IgM is indicative of immunity to HAV via past infection or vaccination.

 

 

HAV Prevention in The VHA

The mainstay of HAV prevention is vaccination with 2 doses of inactivated, single-antigen hepatitis A vaccine or 3 doses of combination (HAV and HBV) vaccine.11 Both single antigen and combination HAV vaccines are safe in immunocompromised and pregnant patients.33-39 The HAV vaccination results in 100% anti-HAV IgG seropositivity among healthy individuals, although immunogenicity might be lower for those who are immunocompromised or with CLD.31,40-47 The VHA recommends HAV immunization, unless contraindicated, for previously unvaccinated 

adults who are at increased risk of contracting HAV and for any other adult who is seeking protection from HAV infection (Table 2).48 Hepatitis A virus vaccination is not specifically recommended for workers in food service, health care, sanitation, or child care.11

In addition to vaccination, addressing risk factors for HAV infection and its complications could reduce the burden of disease. For instance, recent outbreaks highlight that homeless individuals and users of injection and noninjection drugs are particularly vulnerable to infections transmitted via fecal-oral contamination. Broad strategies to address homelessness and related sanitation concerns are needed to help reduce the likelihood of future HAV outbreaks.49 Specific measures to combat HAV include providing access to clean water, adequate hygiene, and clean needles for people who inject drugs.11 Hepatitis A virus can be destroyed by heating food to ≥ 185 °F for at least 1 minute, chlorinating contaminated water, or cleaning contaminated surfaces with a solution of household bleach and water.50 Moreover, it is important to identify and treat risk factors for complications of HAV infection. This includes identifying individuals with HCV and ensuring that they are immune to HAV, given data that HCV-infected individuals are at increased risk of fulminant hepatic failure from HAV.12,13

Active-duty service members have long been considered at higher risk of HAV infections due to deployments in endemic areas and exposure to contaminated food and water.51,52 Shortly after the FDA approved HAV vaccination in 1995, the Department of Defense (DoD) mandated screening and HAV immunization for all incoming active-duty service members and those deployed to areas of high endemicity.53 However, US veterans who were discharged before the adoption of universal HAV vaccination remain at increased risk for HAV infection, particularly given the high prevalence of CLD, homelessness, and substance use disorder (SUD) in this cohort.54-56 Given the importance of HAV prevention for high-risk individuals, an analysis was performed to determine rates of HAV vaccination and testing within VA-enrolled individuals with selected risk factors for HAV acquisition or complications.

Methods

A cross-sectional analysis of veterans in VA care from June 1, 2016 to June 1, 2017 was performed to determine national rates of HAV susceptibility among patients with HCV exposure, homelessness, SUD, or HIV infection. The definitions of homelessness, SUD (alcohol, cannabis, opioid, sedatives, hallucinogens, inhalants, stimulants, or tobacco), and HIV infection were based on the presence of appropriate ICD-9 or ICD-10 codes. History of HCV exposure was based on a positive HCV antibody test. Presence of HAV vaccination was determined based on CPT codes for administration of the single-antigen HAV vaccination or combination HAV/HBV vaccination.

While HIV infection is not independently considered an indication for HAV vaccination, the authors included this group given its high proportion of patients with other risk factors, including MSM and IV drug use. All data were obtained from the VA Corporate Data Warehouse (CDW), a comprehensive national repository of all laboratory, diagnosis, and prescription results (including vaccines) within the VHA since 1999.

Hepatitis A virus nonsusceptibility was defined as (1) documented receipt of HAV vaccination within the VHA; (2) anti-HAV IgG antibody testing within the VHA; or (3) active-duty service after October 1997. It was considered likely that patients who received HAV testing either showed evidence of HAV immunity (eg, positive anti-HAV IgG) or were anti-HAV IgG negative and subsequently immunized. Therefore, patients with anti-HAV IgG antibody testing were counted presumptively as nonsusceptible. The DoD implemented a universal HAV vaccination policy in 1995, therefore, 1997 was chosen as a time at which the military’s universal HAV vaccination campaign was likely to have achieved near 100% vaccination coverage of active-duty military.

 

Results

The cohort included 5,896,451 patients in VA care, including 381,628 (6.5%) who were homeless, 455,344 (7.7%) with SUD, 225,889 (3.8%) with a lifetime history of positive HCV antibody (indicating past HCV exposure), and 29,166 (0.5%) with HIV infection.

National rates of HAV susceptibility were lowest among patients with HIV (mean 21.8%, facility range 0%-56.5%) followed by SUD (mean 47.4%, facility range 3.8%-70.4%), homelessness (mean 48.4%, facility range 5.9%-69.3%), and HCV exposure (mean 48.9%, facility range 30.5%-71.6%) (Table 3).

 

 

There was wide geographic variability in rates of HAV susceptibility (Figure 1). 

When limiting the analysis to patients with confirmed vaccination within the VHA or active duty military service after October 1997, VA facilities in states with active outbreaks had a mean HAV vaccination rate of 38.1% (range 31.5%-44.3%) among patients who were homeless and 42.0% (range 33.8%-49.0%) among patients with SUD.

Discussion

Widespread HAV vaccination has decreased the incidence of HAV infection in the US dramatically. Nevertheless, recent outbreaks demonstrate that substantial population susceptibility and associated risk for HAV-related morbidity and mortality remains, particularly in high-risk populations. Although the VHA has not experienced a significant increase in acute HAV infections to date, this cross-sectional analysis highlights that a large proportion of VA patients in traditionally high-risk groups remain susceptible to HAV infection.

Strengths

Strengths of this analysis include a current reflection of HAV susceptibility within the national VHA, thus informing HAV testing and vaccination strategies. This study also involves a very large cohort, which is possible because the VHA is the largest integrated healthcare system in the US. Lastly, because the VHA uses electronic medical records, there was nearly complete capture of HAV vaccinations and testing obtained through the VHA.

Limitations

This cross-sectional analysis has several potential limitations. First, findings may not be generalizable outside the VHA. In addition, determination of homelessness, substance abuse, and HIV infection were based on ICD-9 and ICD-10 codes, which have been used in previous studies but may be subject to misclassification. The authors deliberately included all patients with positive HCV antibody testing to include those with current or prior risk factors for HAV acquisition. This population does not reflect patients with HCV viremia who received HAV testing or vaccination. Lastly, misattribution of HAV susceptibility could have occurred if patients with negative HAV IgG results were not vaccinated or if patients previously received HAV vaccination outside the VHA.

Conclusion

To mitigate the risk of future HAV outbreaks, continued efforts should be made to increase vaccination among high-risk groups, improve awareness of additional prevention measures, and address risk factors for HAV acquisition, particularly in areas with active outbreaks. Further study is suggested to identify geographic areas with large caseloads of at-risk patients and to highlight best practices utilized by VHA facilities that achieved high vaccine coverage rates. Recommended approaches likely will need to include efforts to improve hygiene and reduce risks for HAV exposure associated with SUD and homelessness.

Click here to read the digital edition.

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37. Nolan T, Bernstein H, Blatter MM, et al. Immunogenicity and safety of an inactivated hepatitis A vaccine administered concomitantly with diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines to children less than 2 years of age. Pediatrics. 2006;118(3):e602-e609.

38. Usonis V, Meriste S, Bakasenas V, et al. Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months. Vaccine. 2005;23(20):2602-2606.

39. Moro PL, Museru OI, Niu M, Lewis P, Broder K. Reports to the Vaccine Adverse Event Reporting System after hepatitis A and hepatitis AB vaccines in pregnant women. Am J Obstet Gynecol. 2014;210(6):561.e1-561.e-6.

40. André FE, D’Hondt E, Delem A, Safary A. Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. Vaccine. 1992;10(suppl 1):S160-S168.

41. Just M, Berger R. Reactogenicity and immunogenicity of inactivated hepatitis A vaccines. Vaccine. 1992;10(suppl 1):S110-S113.

42. McMahon BJ, Williams J, Bulkow L, et al. Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and Native and non-Native adults. J Infect Dis. 1995;171(3):676-679.

43. Balcarek KB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis. 1995;171(suppl 1):S70-S72.

44. Bell BP, Negus S, Fiore AE, et al. Immunogenicity of an inactivated hepatitis A vaccine in infants and young children. Pediatr Infect Dis J. 2007;26(2):116-122.

45. Arguedas MR, Johnson A, Eloubeidi MA, Fallon MB. Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients. Hepatology. 2001;34(1):28-31.

46. Overton ET, Nurutdinova D, Sungkanuparph S, Seyfried W, Groger RK, Powderly WG. Predictors of immunity after hepatitis A vaccination in HIV-infected persons. J Viral Hepat. 2007;14(3):189-193.

47. Askling HH, Rombo L, van Vollenhoven R, et al. Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study. Travel Med Infect Dis. 2014;12(2):134-142.

48. US Department of Veterans Affairs. VHA national hepatitis A immunization guidelines. http://vaww.prevention.va.gov/CPS/Hepatitis_A_Immunization.asp. Nonpublic document. Source not verified.

49. Kushel M. Hepatitis A outbreak in California - addressing the root cause. N Engl J Med. 2018;378(3):211-213.

50. Millard J, Appleton H, Parry JV. Studies on heat inactivation of hepatitis A virus with special reference to shellfish. Part 1. Procedures for infection and recovery of virus from laboratory-maintained cockles. Epidemiol Infect. 1987;98(3):397-414.

51. Hoke CH, Jr., Binn LN, Egan JE, et al. Hepatitis A in the US Army: epidemiology and vaccine development. Vaccine. 1992;10(suppl 1):S75-S79.

52. Dooley DP. History of U.S. military contributions to the study of viral hepatitis. Mil Med. 2005;170(suppl 4):71-76.

53. Grabenstein JD, Pittman PR, Greenwood JT, Engler RJ. Immunization to protect the US Armed Forces: heritage, current practice, and prospects. Epidemiol Rev. 2006;28:3-26.

54. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013. Gastroenterology. 2015;149(6):1471-1482.e1475; quiz e17-e18.

55. Fargo J, Metraux S, Byrne T, et al. Prevalence and risk of homelessness among US veterans. Prev Chronic Dis. 2012;9:E45.

56. Teeters JB, Lancaster CL, Brown DG, Back SE. Substance use disorders in military veterans: prevalence and treatment challenges. Subst Abuse Rehabil. 2017;8:69-77.

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31. Plumb ID, Bulkow LR, Bruce MG, et al. Persistence of antibody to Hepatitis A virus 20 years after receipt of Hepatitis A vaccine in Alaska. J Viral Hepat. 2017;24(7):608-612.

32. Koff RS. Clinical manifestations and diagnosis of hepatitis A virus infection. Vaccine. 1992;10 (suppl 1):S15-S17.

33. Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ, André FE. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis. 1995;171(suppl 1):S44-S49.

34. Ambrosch F, André FE, Delem A, et al. Simultaneous vaccination against hepatitis A and B: results of a controlled study. Vaccine. 1992;10(suppl 1):S142-S145.

35. Gil A, González A, Dal-Ré R, Calero JR. Interference assessment of yellow fever vaccine with the immune response to a single-dose inactivated hepatitis A vaccine (1440 EL.U.). A controlled study in adults. Vaccine. 1996;14(11):1028-1030.

36. Jong EC, Kaplan KM, Eves KA, Taddeo CA, Lakkis HD, Kuter BJ. An open randomized study of inactivated hepatitis A vaccine administered concomitantly with typhoid fever and yellow fever vaccines. J Travel Med. 2002;9(2):66-70.

37. Nolan T, Bernstein H, Blatter MM, et al. Immunogenicity and safety of an inactivated hepatitis A vaccine administered concomitantly with diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines to children less than 2 years of age. Pediatrics. 2006;118(3):e602-e609.

38. Usonis V, Meriste S, Bakasenas V, et al. Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months. Vaccine. 2005;23(20):2602-2606.

39. Moro PL, Museru OI, Niu M, Lewis P, Broder K. Reports to the Vaccine Adverse Event Reporting System after hepatitis A and hepatitis AB vaccines in pregnant women. Am J Obstet Gynecol. 2014;210(6):561.e1-561.e-6.

40. André FE, D’Hondt E, Delem A, Safary A. Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. Vaccine. 1992;10(suppl 1):S160-S168.

41. Just M, Berger R. Reactogenicity and immunogenicity of inactivated hepatitis A vaccines. Vaccine. 1992;10(suppl 1):S110-S113.

42. McMahon BJ, Williams J, Bulkow L, et al. Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and Native and non-Native adults. J Infect Dis. 1995;171(3):676-679.

43. Balcarek KB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis. 1995;171(suppl 1):S70-S72.

44. Bell BP, Negus S, Fiore AE, et al. Immunogenicity of an inactivated hepatitis A vaccine in infants and young children. Pediatr Infect Dis J. 2007;26(2):116-122.

45. Arguedas MR, Johnson A, Eloubeidi MA, Fallon MB. Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients. Hepatology. 2001;34(1):28-31.

46. Overton ET, Nurutdinova D, Sungkanuparph S, Seyfried W, Groger RK, Powderly WG. Predictors of immunity after hepatitis A vaccination in HIV-infected persons. J Viral Hepat. 2007;14(3):189-193.

47. Askling HH, Rombo L, van Vollenhoven R, et al. Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study. Travel Med Infect Dis. 2014;12(2):134-142.

48. US Department of Veterans Affairs. VHA national hepatitis A immunization guidelines. http://vaww.prevention.va.gov/CPS/Hepatitis_A_Immunization.asp. Nonpublic document. Source not verified.

49. Kushel M. Hepatitis A outbreak in California - addressing the root cause. N Engl J Med. 2018;378(3):211-213.

50. Millard J, Appleton H, Parry JV. Studies on heat inactivation of hepatitis A virus with special reference to shellfish. Part 1. Procedures for infection and recovery of virus from laboratory-maintained cockles. Epidemiol Infect. 1987;98(3):397-414.

51. Hoke CH, Jr., Binn LN, Egan JE, et al. Hepatitis A in the US Army: epidemiology and vaccine development. Vaccine. 1992;10(suppl 1):S75-S79.

52. Dooley DP. History of U.S. military contributions to the study of viral hepatitis. Mil Med. 2005;170(suppl 4):71-76.

53. Grabenstein JD, Pittman PR, Greenwood JT, Engler RJ. Immunization to protect the US Armed Forces: heritage, current practice, and prospects. Epidemiol Rev. 2006;28:3-26.

54. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013. Gastroenterology. 2015;149(6):1471-1482.e1475; quiz e17-e18.

55. Fargo J, Metraux S, Byrne T, et al. Prevalence and risk of homelessness among US veterans. Prev Chronic Dis. 2012;9:E45.

56. Teeters JB, Lancaster CL, Brown DG, Back SE. Substance use disorders in military veterans: prevalence and treatment challenges. Subst Abuse Rehabil. 2017;8:69-77.

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