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Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.

Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.

This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.

While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.

“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.

“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”

The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).

Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.

“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”

In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.

Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.

For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).

Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”

The investigators reported no external funding or conflicts of interest.

SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.

Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.

Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.

This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.

While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.

“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.

“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”

The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).

Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.

“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”

In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.

Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.

For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).

Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”

The investigators reported no external funding or conflicts of interest.

SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.

Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.

Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.

This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.

While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.

“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.

“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”

The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).

Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.

“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”

In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.

Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.

For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).

Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”

The investigators reported no external funding or conflicts of interest.

SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.

Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.

Graça Victoria/Thinkstockphotos.com

The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.

During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.

In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.

The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.

The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.

They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.

The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.

Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.

Graça Victoria/Thinkstockphotos.com

The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.

During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.

In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.

The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.

The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.

They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.

The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.

Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.

Graça Victoria/Thinkstockphotos.com

The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.

During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.

In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.

The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.

The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.

They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.

The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.

Curing hepatitis C virus (HCV) infection without addressing the high rate of alcohol use disorder in many patients may undermine the benefits of treatment to long-term liver health, according to the results of a large cohort study.

Katarzyna Bialasiewicz/Thinkstock

Because excess alcohol use is known to accelerate liver disease progression, researchers Risha Irvin, MD, and her colleagues from Johns Hopkins University, Baltimore, examined the prevalence of alcohol use in HCV-infected people who inject drugs (PWID). Their study examined the prevalence and associated correlates of alcohol use (Addictive Behaviors 2019;96:56-61).

They followed a large cohort of 1,623 HCV-antibody positive PWID from 2005 to 2013 from the AIDS Linked to the Intravenous Experience (ALIVE) study. They characterized alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Multivariable logistic regression with generalized estimated equations was used to examine sociodemographic, clinical, and substance use correlates of alcohol use.

At baseline, the median age was 47 years, 67% were men, 81% were black, and 34% were HIV positive. The majority (60%) reported injection drug use in the prior 6 months, while 46% reported noninjection cocaine or heroin, 31% reported street-acquired prescription drugs, and 22% reported marijuana use in the same time period. According to the AUDIT-C results, 41% of the patients reported no alcohol use, 21% reported moderate alcohol use, and 38% reported heavy alcohol use at their baseline visit.

The factors that were significantly associated with heavy alcohol use included male sex, black race, income of $5,000 or less, a Center for Epidemiologic Studies Depression Scale (range 0-60) score of 23 or greater, being homeless, being incarcerated, marijuana use, use of street-acquired prescription drugs, noninjection cocaine/heroin, injection drug use, and cigarette smoking. In a model that included the composite summary variable for substance use intensity, one drug type (adjusted odds ratio, 1.92), two drug types (AOR, 2.93), and three drug types (AOR, 3.65) were significantly associated with heavy alcohol use.

“While clinicians are undoubtedly concerned about any level of alcohol use in the setting of HCV infection due to the acceleration of liver fibrosis, there is particular concern for individuals with heavy alcohol use and their increased risk for cirrhosis and liver failure even after HCV cure. Without intervention, alcohol use will persist after HCV is cured with the potential to undermine the benefit of HCV cure. Therefore, our data point to the need to invest in and develop programs that effectively address alcohol use and co-occurring substance use in this population of PWID with HCV,” the researchers concluded.

The study was supported by the U.S. National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, and the National Institute on Alcohol Abuse and Alcoholism. The authors declared that they had no conflicts.

mlesney@mdedge.com

SOURCE: Irvin R et al. Addictive Behaviors. 2019;96:56-61.

Curing hepatitis C virus (HCV) infection without addressing the high rate of alcohol use disorder in many patients may undermine the benefits of treatment to long-term liver health, according to the results of a large cohort study.

Katarzyna Bialasiewicz/Thinkstock

Because excess alcohol use is known to accelerate liver disease progression, researchers Risha Irvin, MD, and her colleagues from Johns Hopkins University, Baltimore, examined the prevalence of alcohol use in HCV-infected people who inject drugs (PWID). Their study examined the prevalence and associated correlates of alcohol use (Addictive Behaviors 2019;96:56-61).

They followed a large cohort of 1,623 HCV-antibody positive PWID from 2005 to 2013 from the AIDS Linked to the Intravenous Experience (ALIVE) study. They characterized alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Multivariable logistic regression with generalized estimated equations was used to examine sociodemographic, clinical, and substance use correlates of alcohol use.

At baseline, the median age was 47 years, 67% were men, 81% were black, and 34% were HIV positive. The majority (60%) reported injection drug use in the prior 6 months, while 46% reported noninjection cocaine or heroin, 31% reported street-acquired prescription drugs, and 22% reported marijuana use in the same time period. According to the AUDIT-C results, 41% of the patients reported no alcohol use, 21% reported moderate alcohol use, and 38% reported heavy alcohol use at their baseline visit.

The factors that were significantly associated with heavy alcohol use included male sex, black race, income of $5,000 or less, a Center for Epidemiologic Studies Depression Scale (range 0-60) score of 23 or greater, being homeless, being incarcerated, marijuana use, use of street-acquired prescription drugs, noninjection cocaine/heroin, injection drug use, and cigarette smoking. In a model that included the composite summary variable for substance use intensity, one drug type (adjusted odds ratio, 1.92), two drug types (AOR, 2.93), and three drug types (AOR, 3.65) were significantly associated with heavy alcohol use.

“While clinicians are undoubtedly concerned about any level of alcohol use in the setting of HCV infection due to the acceleration of liver fibrosis, there is particular concern for individuals with heavy alcohol use and their increased risk for cirrhosis and liver failure even after HCV cure. Without intervention, alcohol use will persist after HCV is cured with the potential to undermine the benefit of HCV cure. Therefore, our data point to the need to invest in and develop programs that effectively address alcohol use and co-occurring substance use in this population of PWID with HCV,” the researchers concluded.

The study was supported by the U.S. National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, and the National Institute on Alcohol Abuse and Alcoholism. The authors declared that they had no conflicts.

mlesney@mdedge.com

SOURCE: Irvin R et al. Addictive Behaviors. 2019;96:56-61.

Curing hepatitis C virus (HCV) infection without addressing the high rate of alcohol use disorder in many patients may undermine the benefits of treatment to long-term liver health, according to the results of a large cohort study.

Katarzyna Bialasiewicz/Thinkstock

Because excess alcohol use is known to accelerate liver disease progression, researchers Risha Irvin, MD, and her colleagues from Johns Hopkins University, Baltimore, examined the prevalence of alcohol use in HCV-infected people who inject drugs (PWID). Their study examined the prevalence and associated correlates of alcohol use (Addictive Behaviors 2019;96:56-61).

They followed a large cohort of 1,623 HCV-antibody positive PWID from 2005 to 2013 from the AIDS Linked to the Intravenous Experience (ALIVE) study. They characterized alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Multivariable logistic regression with generalized estimated equations was used to examine sociodemographic, clinical, and substance use correlates of alcohol use.

At baseline, the median age was 47 years, 67% were men, 81% were black, and 34% were HIV positive. The majority (60%) reported injection drug use in the prior 6 months, while 46% reported noninjection cocaine or heroin, 31% reported street-acquired prescription drugs, and 22% reported marijuana use in the same time period. According to the AUDIT-C results, 41% of the patients reported no alcohol use, 21% reported moderate alcohol use, and 38% reported heavy alcohol use at their baseline visit.

The factors that were significantly associated with heavy alcohol use included male sex, black race, income of $5,000 or less, a Center for Epidemiologic Studies Depression Scale (range 0-60) score of 23 or greater, being homeless, being incarcerated, marijuana use, use of street-acquired prescription drugs, noninjection cocaine/heroin, injection drug use, and cigarette smoking. In a model that included the composite summary variable for substance use intensity, one drug type (adjusted odds ratio, 1.92), two drug types (AOR, 2.93), and three drug types (AOR, 3.65) were significantly associated with heavy alcohol use.

“While clinicians are undoubtedly concerned about any level of alcohol use in the setting of HCV infection due to the acceleration of liver fibrosis, there is particular concern for individuals with heavy alcohol use and their increased risk for cirrhosis and liver failure even after HCV cure. Without intervention, alcohol use will persist after HCV is cured with the potential to undermine the benefit of HCV cure. Therefore, our data point to the need to invest in and develop programs that effectively address alcohol use and co-occurring substance use in this population of PWID with HCV,” the researchers concluded.

The study was supported by the U.S. National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, and the National Institute on Alcohol Abuse and Alcoholism. The authors declared that they had no conflicts.

mlesney@mdedge.com

SOURCE: Irvin R et al. Addictive Behaviors. 2019;96:56-61.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

gtwachtman@mdedge.com

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

gtwachtman@mdedge.com

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

gtwachtman@mdedge.com

A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.

Copyright Eraxion/Thinkstock

They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.

They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.

“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.

The authors declared that they had no conflicts.

mlesney@mdedge.com

SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.

A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.

Copyright Eraxion/Thinkstock

They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.

They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.

“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.

The authors declared that they had no conflicts.

mlesney@mdedge.com

SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.

A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.

Copyright Eraxion/Thinkstock

They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.

They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.

“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.

The authors declared that they had no conflicts.

mlesney@mdedge.com

SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.

Assessment of a large cohort of hepatitis C virus (HCV)–infected patients revealed a high prevalence of current or past hepatitis B virus. However, within this cohort, there were notable gaps in HBV testing, directed care, and vaccination, according to Aaron M. Harris, MD, of the Centers for Disease Control and Prevention.

Betty Partin/CDC

Dr. Harris and his colleagues abstracted patient-level data from the Grady Health System EHR in August 2016 to create an HCV patient registry. They found that, among 4,224 HCV-infected patients, 3,629 (86%) had test results for the hepatitis B surface antigen (HBsAg), with 43 (1.2%) being HBsAg positive.

“Our results identified a gap in care as a minority of HBsAg-positive patients with HCV coinfection received HBV DNA and/or e-antigen [HBeAg] testing,” the researchers stated.

Overall, only 2,342 (55.4%) patients had test results for all three HBV serologic markers. Among these, 789 (33.7%) were anti-HBc positive only, 678 (28.9%) were anti-HBc/anti-HBs positive, 190 (8.1%) were anti-HBs positive only, and 642 (27.4%) were HBV susceptible. In addition, only 50% of the HBV-susceptible patients received at least one dose of hepatitis B vaccine, according to the report published in Vaccine.

“Strategies are needed to increase hepatitis B testing, linkage to hepatitis B–directed care of HBV/HCV-coinfected patients, and to increase uptake in hepatitis B vaccination for HCV-infected patients within the Grady Health System,” the researchers concluded.

The study was funded by the CDC and the authors reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Harris AM et al. Vaccine. 2019;37:2188-93.

Assessment of a large cohort of hepatitis C virus (HCV)–infected patients revealed a high prevalence of current or past hepatitis B virus. However, within this cohort, there were notable gaps in HBV testing, directed care, and vaccination, according to Aaron M. Harris, MD, of the Centers for Disease Control and Prevention.

Betty Partin/CDC

Dr. Harris and his colleagues abstracted patient-level data from the Grady Health System EHR in August 2016 to create an HCV patient registry. They found that, among 4,224 HCV-infected patients, 3,629 (86%) had test results for the hepatitis B surface antigen (HBsAg), with 43 (1.2%) being HBsAg positive.

“Our results identified a gap in care as a minority of HBsAg-positive patients with HCV coinfection received HBV DNA and/or e-antigen [HBeAg] testing,” the researchers stated.

Overall, only 2,342 (55.4%) patients had test results for all three HBV serologic markers. Among these, 789 (33.7%) were anti-HBc positive only, 678 (28.9%) were anti-HBc/anti-HBs positive, 190 (8.1%) were anti-HBs positive only, and 642 (27.4%) were HBV susceptible. In addition, only 50% of the HBV-susceptible patients received at least one dose of hepatitis B vaccine, according to the report published in Vaccine.

“Strategies are needed to increase hepatitis B testing, linkage to hepatitis B–directed care of HBV/HCV-coinfected patients, and to increase uptake in hepatitis B vaccination for HCV-infected patients within the Grady Health System,” the researchers concluded.

The study was funded by the CDC and the authors reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Harris AM et al. Vaccine. 2019;37:2188-93.

Assessment of a large cohort of hepatitis C virus (HCV)–infected patients revealed a high prevalence of current or past hepatitis B virus. However, within this cohort, there were notable gaps in HBV testing, directed care, and vaccination, according to Aaron M. Harris, MD, of the Centers for Disease Control and Prevention.

Betty Partin/CDC

Dr. Harris and his colleagues abstracted patient-level data from the Grady Health System EHR in August 2016 to create an HCV patient registry. They found that, among 4,224 HCV-infected patients, 3,629 (86%) had test results for the hepatitis B surface antigen (HBsAg), with 43 (1.2%) being HBsAg positive.

“Our results identified a gap in care as a minority of HBsAg-positive patients with HCV coinfection received HBV DNA and/or e-antigen [HBeAg] testing,” the researchers stated.

Overall, only 2,342 (55.4%) patients had test results for all three HBV serologic markers. Among these, 789 (33.7%) were anti-HBc positive only, 678 (28.9%) were anti-HBc/anti-HBs positive, 190 (8.1%) were anti-HBs positive only, and 642 (27.4%) were HBV susceptible. In addition, only 50% of the HBV-susceptible patients received at least one dose of hepatitis B vaccine, according to the report published in Vaccine.

“Strategies are needed to increase hepatitis B testing, linkage to hepatitis B–directed care of HBV/HCV-coinfected patients, and to increase uptake in hepatitis B vaccination for HCV-infected patients within the Grady Health System,” the researchers concluded.

The study was funded by the CDC and the authors reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Harris AM et al. Vaccine. 2019;37:2188-93.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

mlesney@mdedge.com

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.