Amy Karon

Atopic eczema was linked with a significantly increased risk of lymphoma, and severe eczema was associated with a twofold increase in non-Hodgkin lymphoma (NHL) risk, according to two matched longitudinal cohort studies from England and Denmark.

“In this study, no evidence was found that people with atopic eczema are at increased risk of most cancers. An exception is the observed association between atopic eczema and lymphoma, particularly NHL, [which] increased with eczema severity,” Kathryn E. Mansfield, PhD, wrote in JAMA Dermatology. Adjusted hazard ratios for NHL in the English cohort were 1.06 (99% CI, 0.90-1.25) for mild atopic eczema, 1.24 (99% CI, 1.04-1.48) for moderate eczema, and 2.08 (99% CI, 1.42-3.04) for severe eczema, reported Dr. Mansfield of the London School of Hygiene and Tropical Medicine and associates.

Past studies of a possible link between atopic eczema and cancer have produced conflicting evidence, which might reflect “two competing theories” – that cancer risk falls with greater immune surveillance, and that cancer risk rises with immune stimulation, the researchers wrote. Immunosuppressive treatment and an impaired skin barrier might also increase the risk of cancer, but the evidence is conflicting.

For the study, they analyzed electronic health records linked with hospital admissions and death records in England and national health registry data from Denmark. The English cohort included 471,970 adults with atopic eczema and 2,239,775 adults without atopic eczema. The Danish cohort was composed of individuals of any age, including 44,945 who had eczema and with 445,673 who did not. Participants were matched based on factors such as age, sex, and primary care practice. The researchers excluded individuals with a history of cancer, apart from nonmelanoma skin cancer or keratinocyte cancer. (For analyses of skin cancer risk, they also excluded individuals with a history of nonmelanoma skin cancer.)

Overall, there was “little evidence” for a link between atopic eczema and cancer (adjusted hazard ratio in England, 1.04; 99% CI, 1.02-1.06; aHR in Denmark, 1.05; 99% CI, 0.95-1.16) or for most specific types of cancer, the investigators wrote.

In England, however, eczema was associated with a significantly increased risk for noncutaneous lymphoma, with an adjusted HRs of 1.19 (99% CI, 1.07-1.34) for NHL, and 1.48 (99% CI, 1.07-2.04) for Hodgkin lymphoma. Lymphoma risk was highest among adults with severe eczema, defined as those who had been prescribed a systemic treatment for their disease, who had received phototherapy, or who had been referred to a specialist or admitted to a hospital for atopic eczema. Point estimates in the Danish cohort also revealed a higher risk for lymphoma among individuals with moderate to severe atopic eczema, compared with those with eczema, but the 99% CIs crossed 1.0.

The findings highlight the need to be aware of, screen for, and study the pathogenesis of heightened lymphoma risk among patients with atopic eczema, said Shawn Demehri, MD, PhD, of the department of dermatology and cancer center, at Massachusetts General Hospital, Boston, who was not involved in the study.

“Prospectively collected data from large cohorts of eczema patients is a strength of this study,” he said in an interview. “However, the age range included in the study is suboptimal for assessing cancer as an outcome. The lower incidence of cancer in younger individuals hinders the ability to detect differences in cancer risk between the two groups.” (Approximately 57% of individuals in the English cohort were aged 18-44 years, while approximately 70% of those in the Danish cohort were less than 18 years.)

Understanding how eczema affects the risk of non-Hodgkin lymphoma is an important future direction of research, Dr. Demehri emphasized. “The landscape of atopic eczema therapeutics has dramatically changed in the recent years. It will be very interesting to determine how new biologics impact cancer risk in eczema patients.”

Partial support for the work was provided by the Wellcome Trust, the Royal Society, the Dagmar Marshalls Fund, and the Aase and Ejnar Danielsens Fund. Dr. Mansfield disclosed support from a Wellcome Trust grant. Her coinvestigators disclosed ties to TARGET-DERM, Pfizer, and GlaxoSmithKline, and from the Wellcome Trust, Medical Research Council, the National Institute for Health Research, the British Heart Foundation, Diabetes UK, and IMI Horizon 2020 funding BIOMAP. Dr. Demehri reported having no relevant conflicts of interest.

SOURCE: Mansfield KE et al. JAMA Dermatol. 2020 Jun 24. doi: 10.1001/jamadermatol.2020.1948.

Atopic eczema was linked with a significantly increased risk of lymphoma, and severe eczema was associated with a twofold increase in non-Hodgkin lymphoma (NHL) risk, according to two matched longitudinal cohort studies from England and Denmark.

“In this study, no evidence was found that people with atopic eczema are at increased risk of most cancers. An exception is the observed association between atopic eczema and lymphoma, particularly NHL, [which] increased with eczema severity,” Kathryn E. Mansfield, PhD, wrote in JAMA Dermatology. Adjusted hazard ratios for NHL in the English cohort were 1.06 (99% CI, 0.90-1.25) for mild atopic eczema, 1.24 (99% CI, 1.04-1.48) for moderate eczema, and 2.08 (99% CI, 1.42-3.04) for severe eczema, reported Dr. Mansfield of the London School of Hygiene and Tropical Medicine and associates.

Past studies of a possible link between atopic eczema and cancer have produced conflicting evidence, which might reflect “two competing theories” – that cancer risk falls with greater immune surveillance, and that cancer risk rises with immune stimulation, the researchers wrote. Immunosuppressive treatment and an impaired skin barrier might also increase the risk of cancer, but the evidence is conflicting.

For the study, they analyzed electronic health records linked with hospital admissions and death records in England and national health registry data from Denmark. The English cohort included 471,970 adults with atopic eczema and 2,239,775 adults without atopic eczema. The Danish cohort was composed of individuals of any age, including 44,945 who had eczema and with 445,673 who did not. Participants were matched based on factors such as age, sex, and primary care practice. The researchers excluded individuals with a history of cancer, apart from nonmelanoma skin cancer or keratinocyte cancer. (For analyses of skin cancer risk, they also excluded individuals with a history of nonmelanoma skin cancer.)

Overall, there was “little evidence” for a link between atopic eczema and cancer (adjusted hazard ratio in England, 1.04; 99% CI, 1.02-1.06; aHR in Denmark, 1.05; 99% CI, 0.95-1.16) or for most specific types of cancer, the investigators wrote.

In England, however, eczema was associated with a significantly increased risk for noncutaneous lymphoma, with an adjusted HRs of 1.19 (99% CI, 1.07-1.34) for NHL, and 1.48 (99% CI, 1.07-2.04) for Hodgkin lymphoma. Lymphoma risk was highest among adults with severe eczema, defined as those who had been prescribed a systemic treatment for their disease, who had received phototherapy, or who had been referred to a specialist or admitted to a hospital for atopic eczema. Point estimates in the Danish cohort also revealed a higher risk for lymphoma among individuals with moderate to severe atopic eczema, compared with those with eczema, but the 99% CIs crossed 1.0.

The findings highlight the need to be aware of, screen for, and study the pathogenesis of heightened lymphoma risk among patients with atopic eczema, said Shawn Demehri, MD, PhD, of the department of dermatology and cancer center, at Massachusetts General Hospital, Boston, who was not involved in the study.

“Prospectively collected data from large cohorts of eczema patients is a strength of this study,” he said in an interview. “However, the age range included in the study is suboptimal for assessing cancer as an outcome. The lower incidence of cancer in younger individuals hinders the ability to detect differences in cancer risk between the two groups.” (Approximately 57% of individuals in the English cohort were aged 18-44 years, while approximately 70% of those in the Danish cohort were less than 18 years.)

Understanding how eczema affects the risk of non-Hodgkin lymphoma is an important future direction of research, Dr. Demehri emphasized. “The landscape of atopic eczema therapeutics has dramatically changed in the recent years. It will be very interesting to determine how new biologics impact cancer risk in eczema patients.”

Partial support for the work was provided by the Wellcome Trust, the Royal Society, the Dagmar Marshalls Fund, and the Aase and Ejnar Danielsens Fund. Dr. Mansfield disclosed support from a Wellcome Trust grant. Her coinvestigators disclosed ties to TARGET-DERM, Pfizer, and GlaxoSmithKline, and from the Wellcome Trust, Medical Research Council, the National Institute for Health Research, the British Heart Foundation, Diabetes UK, and IMI Horizon 2020 funding BIOMAP. Dr. Demehri reported having no relevant conflicts of interest.

SOURCE: Mansfield KE et al. JAMA Dermatol. 2020 Jun 24. doi: 10.1001/jamadermatol.2020.1948.

Atopic eczema was linked with a significantly increased risk of lymphoma, and severe eczema was associated with a twofold increase in non-Hodgkin lymphoma (NHL) risk, according to two matched longitudinal cohort studies from England and Denmark.

“In this study, no evidence was found that people with atopic eczema are at increased risk of most cancers. An exception is the observed association between atopic eczema and lymphoma, particularly NHL, [which] increased with eczema severity,” Kathryn E. Mansfield, PhD, wrote in JAMA Dermatology. Adjusted hazard ratios for NHL in the English cohort were 1.06 (99% CI, 0.90-1.25) for mild atopic eczema, 1.24 (99% CI, 1.04-1.48) for moderate eczema, and 2.08 (99% CI, 1.42-3.04) for severe eczema, reported Dr. Mansfield of the London School of Hygiene and Tropical Medicine and associates.

Past studies of a possible link between atopic eczema and cancer have produced conflicting evidence, which might reflect “two competing theories” – that cancer risk falls with greater immune surveillance, and that cancer risk rises with immune stimulation, the researchers wrote. Immunosuppressive treatment and an impaired skin barrier might also increase the risk of cancer, but the evidence is conflicting.

For the study, they analyzed electronic health records linked with hospital admissions and death records in England and national health registry data from Denmark. The English cohort included 471,970 adults with atopic eczema and 2,239,775 adults without atopic eczema. The Danish cohort was composed of individuals of any age, including 44,945 who had eczema and with 445,673 who did not. Participants were matched based on factors such as age, sex, and primary care practice. The researchers excluded individuals with a history of cancer, apart from nonmelanoma skin cancer or keratinocyte cancer. (For analyses of skin cancer risk, they also excluded individuals with a history of nonmelanoma skin cancer.)

Overall, there was “little evidence” for a link between atopic eczema and cancer (adjusted hazard ratio in England, 1.04; 99% CI, 1.02-1.06; aHR in Denmark, 1.05; 99% CI, 0.95-1.16) or for most specific types of cancer, the investigators wrote.

In England, however, eczema was associated with a significantly increased risk for noncutaneous lymphoma, with an adjusted HRs of 1.19 (99% CI, 1.07-1.34) for NHL, and 1.48 (99% CI, 1.07-2.04) for Hodgkin lymphoma. Lymphoma risk was highest among adults with severe eczema, defined as those who had been prescribed a systemic treatment for their disease, who had received phototherapy, or who had been referred to a specialist or admitted to a hospital for atopic eczema. Point estimates in the Danish cohort also revealed a higher risk for lymphoma among individuals with moderate to severe atopic eczema, compared with those with eczema, but the 99% CIs crossed 1.0.

The findings highlight the need to be aware of, screen for, and study the pathogenesis of heightened lymphoma risk among patients with atopic eczema, said Shawn Demehri, MD, PhD, of the department of dermatology and cancer center, at Massachusetts General Hospital, Boston, who was not involved in the study.

“Prospectively collected data from large cohorts of eczema patients is a strength of this study,” he said in an interview. “However, the age range included in the study is suboptimal for assessing cancer as an outcome. The lower incidence of cancer in younger individuals hinders the ability to detect differences in cancer risk between the two groups.” (Approximately 57% of individuals in the English cohort were aged 18-44 years, while approximately 70% of those in the Danish cohort were less than 18 years.)

Understanding how eczema affects the risk of non-Hodgkin lymphoma is an important future direction of research, Dr. Demehri emphasized. “The landscape of atopic eczema therapeutics has dramatically changed in the recent years. It will be very interesting to determine how new biologics impact cancer risk in eczema patients.”

Partial support for the work was provided by the Wellcome Trust, the Royal Society, the Dagmar Marshalls Fund, and the Aase and Ejnar Danielsens Fund. Dr. Mansfield disclosed support from a Wellcome Trust grant. Her coinvestigators disclosed ties to TARGET-DERM, Pfizer, and GlaxoSmithKline, and from the Wellcome Trust, Medical Research Council, the National Institute for Health Research, the British Heart Foundation, Diabetes UK, and IMI Horizon 2020 funding BIOMAP. Dr. Demehri reported having no relevant conflicts of interest.

SOURCE: Mansfield KE et al. JAMA Dermatol. 2020 Jun 24. doi: 10.1001/jamadermatol.2020.1948.

Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.

“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.^®

Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).

Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.

“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).

Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).

Dr. Mehtsun reported having no relevant conflicts of interest.

SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.

Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.

“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.^®

Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).

Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.

“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).

Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).

Dr. Mehtsun reported having no relevant conflicts of interest.

SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.

Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.

“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.^®

Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).

Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.

“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).

Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).

Dr. Mehtsun reported having no relevant conflicts of interest.

SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.

Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.

The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.^®

“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”

Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.

To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.

Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.

After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”

She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”

Dr. Lopes reported having no conflicts of interest.

SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.

Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.

The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.^®

“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”

Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.

To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.

Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.

After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”

She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”

Dr. Lopes reported having no conflicts of interest.

SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.

Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.

The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.^®

“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”

Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.

To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.

Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.

After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”

She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”

Dr. Lopes reported having no conflicts of interest.

SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.

High-dose oral famotidine might improve cardinal symptoms of COVID-19 infection, according to the findings of a small outpatient case series and a subsequent retrospective study.

After developing COVID-19 symptoms, the 10 patients in the case series began self-medicating with 60-240 mg famotidine daily over a median of 11 days. “All patients reported marked improvements of disease-related symptoms after starting famotidine,” first author Tobias Janowitz, MD, PhD, of Cold Spring Harbor Laboratory, N.Y., and associates wrote in Gut.

Improvements began within 24-48 hours of starting on the histamine-2 receptor antagonist. By 14 days after treatment initiation, all patients reported near-normalization of both respiratory and systemic symptoms, the researchers reported.

The patients were 23-71 years old. Seven tested positive for COVID-19, two had antibodies to COVID-19, and one had a clinical diagnosis of COVID-19 without laboratory confirmation. Over a median of 11 days (range, 5-21 days), six patients self-administered 80 mg famotidine three times daily and four self-administered lower amounts – from 60 to 150 mg of famotidine daily, divided into two or three doses. Patients started on famotidine between 2 and 26 days after symptom onset.

Through phone interviews and questionnaires, the researchers ascertained changes in cough, dyspnea, fatigue, headache, anosmia, and general unwellness by using a modified four-point Eastern Cooperative Oncology Group (ECOG) performance status scale. Improvements were seen across all symptom categories, and respiratory symptoms improved faster than systemic symptoms. Apart from two cases of persistent anosmia, symptoms resolved completely within 14 days of starting famotidine.

Seven patients reported no side effects of famotidine; one reported grade 1 dizziness and infrequent perceptions of tachycardia; one reported grade 1 dizziness, dry skin, and insomnia; and one reported grade 1 gastrointestinal symptoms and temporary forgetfulness. “Other than forgetfulness, all of these side effects are listed in the prescription information for famotidine, and all side effects resolved on discontinuation of famotidine,” the investigators wrote.

While the findings are intriguing, Dr. Janowitz and associates cautioned against overinterpretation of them. Another expert agreed: “This is a preliminary study based on a hypothesized antiviral effect. It’s important to know that it doesn’t really prove it works,” said Amesh Adalja, MD, senior scholar at the Johns Hopkins University Center for Health Security, Baltimore, and a spokesperson for the Infectious Diseases Society of America, during an interview with MDedge.

These patients might have improved anyway, without self-administering famotidine, said Dr. Adalja, who was not involved in the study.

Furthermore, the mechanism by which famotidine might act on COVID-19 remains unclear. The drug “could have a viral target, for example, one of the viral proteases, or a host target, resulting, for example, in modulation of the immunological response to the virus,” Dr. Janowitz and associates wrote.

Dr. Adalja noted that many compounds show effects against COVID-19 that are not well understood. He called for randomized trials to evaluate the biological plausibility of famotidine use, and its potential efficacy.

“This is a cheap, over-the-counter drug, but no drug is without side effects,” he added. “We need to know whether it works.”

Based on the case series findings, researchers conducted another retrospective study of patients hospitalized with COVID-19 infection. Those who were incidentally taking famotidine before or at hospitalization had a significantly reduced risk of intubation or death, with a hazard ratio of 0.43 (Gastroenterology. 2020 May 22. doi: 10.1053/j.gastro.2020.05.053)

The National Institutes of Health provided partial support. The investigators reported having no conflicts of interest.

SOURCE: Janowitz T et al. Gut. 2020 Jun 4. doi: 10.1136/gutjnl-2020-321852.

High-dose oral famotidine might improve cardinal symptoms of COVID-19 infection, according to the findings of a small outpatient case series and a subsequent retrospective study.

After developing COVID-19 symptoms, the 10 patients in the case series began self-medicating with 60-240 mg famotidine daily over a median of 11 days. “All patients reported marked improvements of disease-related symptoms after starting famotidine,” first author Tobias Janowitz, MD, PhD, of Cold Spring Harbor Laboratory, N.Y., and associates wrote in Gut.

Improvements began within 24-48 hours of starting on the histamine-2 receptor antagonist. By 14 days after treatment initiation, all patients reported near-normalization of both respiratory and systemic symptoms, the researchers reported.

The patients were 23-71 years old. Seven tested positive for COVID-19, two had antibodies to COVID-19, and one had a clinical diagnosis of COVID-19 without laboratory confirmation. Over a median of 11 days (range, 5-21 days), six patients self-administered 80 mg famotidine three times daily and four self-administered lower amounts – from 60 to 150 mg of famotidine daily, divided into two or three doses. Patients started on famotidine between 2 and 26 days after symptom onset.

Through phone interviews and questionnaires, the researchers ascertained changes in cough, dyspnea, fatigue, headache, anosmia, and general unwellness by using a modified four-point Eastern Cooperative Oncology Group (ECOG) performance status scale. Improvements were seen across all symptom categories, and respiratory symptoms improved faster than systemic symptoms. Apart from two cases of persistent anosmia, symptoms resolved completely within 14 days of starting famotidine.

Seven patients reported no side effects of famotidine; one reported grade 1 dizziness and infrequent perceptions of tachycardia; one reported grade 1 dizziness, dry skin, and insomnia; and one reported grade 1 gastrointestinal symptoms and temporary forgetfulness. “Other than forgetfulness, all of these side effects are listed in the prescription information for famotidine, and all side effects resolved on discontinuation of famotidine,” the investigators wrote.

While the findings are intriguing, Dr. Janowitz and associates cautioned against overinterpretation of them. Another expert agreed: “This is a preliminary study based on a hypothesized antiviral effect. It’s important to know that it doesn’t really prove it works,” said Amesh Adalja, MD, senior scholar at the Johns Hopkins University Center for Health Security, Baltimore, and a spokesperson for the Infectious Diseases Society of America, during an interview with MDedge.

These patients might have improved anyway, without self-administering famotidine, said Dr. Adalja, who was not involved in the study.

Furthermore, the mechanism by which famotidine might act on COVID-19 remains unclear. The drug “could have a viral target, for example, one of the viral proteases, or a host target, resulting, for example, in modulation of the immunological response to the virus,” Dr. Janowitz and associates wrote.

Dr. Adalja noted that many compounds show effects against COVID-19 that are not well understood. He called for randomized trials to evaluate the biological plausibility of famotidine use, and its potential efficacy.

“This is a cheap, over-the-counter drug, but no drug is without side effects,” he added. “We need to know whether it works.”

Based on the case series findings, researchers conducted another retrospective study of patients hospitalized with COVID-19 infection. Those who were incidentally taking famotidine before or at hospitalization had a significantly reduced risk of intubation or death, with a hazard ratio of 0.43 (Gastroenterology. 2020 May 22. doi: 10.1053/j.gastro.2020.05.053)

The National Institutes of Health provided partial support. The investigators reported having no conflicts of interest.

SOURCE: Janowitz T et al. Gut. 2020 Jun 4. doi: 10.1136/gutjnl-2020-321852.

High-dose oral famotidine might improve cardinal symptoms of COVID-19 infection, according to the findings of a small outpatient case series and a subsequent retrospective study.

After developing COVID-19 symptoms, the 10 patients in the case series began self-medicating with 60-240 mg famotidine daily over a median of 11 days. “All patients reported marked improvements of disease-related symptoms after starting famotidine,” first author Tobias Janowitz, MD, PhD, of Cold Spring Harbor Laboratory, N.Y., and associates wrote in Gut.

Improvements began within 24-48 hours of starting on the histamine-2 receptor antagonist. By 14 days after treatment initiation, all patients reported near-normalization of both respiratory and systemic symptoms, the researchers reported.

The patients were 23-71 years old. Seven tested positive for COVID-19, two had antibodies to COVID-19, and one had a clinical diagnosis of COVID-19 without laboratory confirmation. Over a median of 11 days (range, 5-21 days), six patients self-administered 80 mg famotidine three times daily and four self-administered lower amounts – from 60 to 150 mg of famotidine daily, divided into two or three doses. Patients started on famotidine between 2 and 26 days after symptom onset.

Through phone interviews and questionnaires, the researchers ascertained changes in cough, dyspnea, fatigue, headache, anosmia, and general unwellness by using a modified four-point Eastern Cooperative Oncology Group (ECOG) performance status scale. Improvements were seen across all symptom categories, and respiratory symptoms improved faster than systemic symptoms. Apart from two cases of persistent anosmia, symptoms resolved completely within 14 days of starting famotidine.

Seven patients reported no side effects of famotidine; one reported grade 1 dizziness and infrequent perceptions of tachycardia; one reported grade 1 dizziness, dry skin, and insomnia; and one reported grade 1 gastrointestinal symptoms and temporary forgetfulness. “Other than forgetfulness, all of these side effects are listed in the prescription information for famotidine, and all side effects resolved on discontinuation of famotidine,” the investigators wrote.

While the findings are intriguing, Dr. Janowitz and associates cautioned against overinterpretation of them. Another expert agreed: “This is a preliminary study based on a hypothesized antiviral effect. It’s important to know that it doesn’t really prove it works,” said Amesh Adalja, MD, senior scholar at the Johns Hopkins University Center for Health Security, Baltimore, and a spokesperson for the Infectious Diseases Society of America, during an interview with MDedge.

These patients might have improved anyway, without self-administering famotidine, said Dr. Adalja, who was not involved in the study.

Furthermore, the mechanism by which famotidine might act on COVID-19 remains unclear. The drug “could have a viral target, for example, one of the viral proteases, or a host target, resulting, for example, in modulation of the immunological response to the virus,” Dr. Janowitz and associates wrote.

Dr. Adalja noted that many compounds show effects against COVID-19 that are not well understood. He called for randomized trials to evaluate the biological plausibility of famotidine use, and its potential efficacy.

“This is a cheap, over-the-counter drug, but no drug is without side effects,” he added. “We need to know whether it works.”

Based on the case series findings, researchers conducted another retrospective study of patients hospitalized with COVID-19 infection. Those who were incidentally taking famotidine before or at hospitalization had a significantly reduced risk of intubation or death, with a hazard ratio of 0.43 (Gastroenterology. 2020 May 22. doi: 10.1053/j.gastro.2020.05.053)

The National Institutes of Health provided partial support. The investigators reported having no conflicts of interest.

SOURCE: Janowitz T et al. Gut. 2020 Jun 4. doi: 10.1136/gutjnl-2020-321852.

Gastrointestinal symptoms affected 26% of hospital employees hospitalized with presumptive COVID-19 infection, according to the results of a study from Wuhan, China.

Among nonmedical personnel in the study (median age, 62 years), 63% of those with GI symptoms were female (P = .03), wrote Zili Zhou of Huazhong University of Science and Technology, Wuhan, China, and associates. Gastrointestinal symptoms correlated significantly with lower hemoglobin levels, increased levels of inflammatory markers, and poorer liver function, but not with clinical complications or mortality, they noted. However, “most patients were still hospitalized at the time of [manuscript] submission, [which made it] difficult to further assess the correlation between GI symptoms and clinical outcomes,” they wrote in Gastroenterology.

Reverse transcriptase polymerase chain reaction has detected COVID-19 in patients’ stool, and COVID-19’s primary receptor for cellular entry, the angiotensin converting enzyme 2 (ACE2) receptor, “is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon,” the investigators wrote. They compared laboratory and clinical findings among 254 adults with and without GI symptoms who were admitted to Wuhan’s main hospital with presumptive COVID-19 pneumonia between December 20, 2019, and February 9, 2020. All patients were employed by the hospital.

Gastrointestinal symptoms affected 26% of patients and most commonly included diarrhea (18%), nausea (8%), vomiting (6%), and abdominal pain (2%), the researchers reported. Arrhythmias and shock were rare, affecting less than 0.5% of patients. A total of 16 patients (6%) died.

The 161 nonmedical staff in the study were older and, therefore, were evaluated separately from medical staff (respective medians, 36 and 62 years; interquartile ranges, 31-41 years and 49-69 years). Among nonmedical staff, GI symptoms correlated with significantly lower hemoglobin levels (117 g/L [range, 106-127] vs. 133 g/L [range, 114-141], P = .03), and significantly higher levels of C-reactive protein (7.3 mg [range, 2.9-6.6] vs. 3.8 mg (1.8-5.8), P = .021) and alanine aminotransferase (64.1 U/L [range, 51.2-64.4] vs. 46.6 U/L [range, 31.9-61.2]; P = .049). Gastrointestinal symptoms also correlated significantly with fatigue, sore throat, and dizziness. Although the nonmedical cohort included five more males than females, females made up nearly two-thirds (63%) of individuals with GI symptoms (P = .03).

Although 25% of medical staff in the study had GI symptoms, GI symptoms did not correlate with other symptoms or with laboratory findings. This might be because “most of the infected medical staff were younger nurses without comorbidities,” the investigators wrote. “In addition, there [was] less delay from the onset of symptoms to hospital admission.”

For the overall cohort, the most prevalent symptoms were fever (84%), fatigue (52%), productive cough (42%), dry cough (42%), and myalgia (34%). Although these symptoms are typical of COVID-19 infection, most patients were not tested for the virus, “which will inevitably lead to several patients without [COVID-19 pneumonia] being included,” the investigators noted.

The National Nature Science Foundation of China provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhou Z et al. Gastroenterology. 2020 Mar 18. doi: 10.1053/j.gastro.2020.03.020.

Gastrointestinal symptoms affected 26% of hospital employees hospitalized with presumptive COVID-19 infection, according to the results of a study from Wuhan, China.

Among nonmedical personnel in the study (median age, 62 years), 63% of those with GI symptoms were female (P = .03), wrote Zili Zhou of Huazhong University of Science and Technology, Wuhan, China, and associates. Gastrointestinal symptoms correlated significantly with lower hemoglobin levels, increased levels of inflammatory markers, and poorer liver function, but not with clinical complications or mortality, they noted. However, “most patients were still hospitalized at the time of [manuscript] submission, [which made it] difficult to further assess the correlation between GI symptoms and clinical outcomes,” they wrote in Gastroenterology.

Reverse transcriptase polymerase chain reaction has detected COVID-19 in patients’ stool, and COVID-19’s primary receptor for cellular entry, the angiotensin converting enzyme 2 (ACE2) receptor, “is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon,” the investigators wrote. They compared laboratory and clinical findings among 254 adults with and without GI symptoms who were admitted to Wuhan’s main hospital with presumptive COVID-19 pneumonia between December 20, 2019, and February 9, 2020. All patients were employed by the hospital.

Gastrointestinal symptoms affected 26% of patients and most commonly included diarrhea (18%), nausea (8%), vomiting (6%), and abdominal pain (2%), the researchers reported. Arrhythmias and shock were rare, affecting less than 0.5% of patients. A total of 16 patients (6%) died.

The 161 nonmedical staff in the study were older and, therefore, were evaluated separately from medical staff (respective medians, 36 and 62 years; interquartile ranges, 31-41 years and 49-69 years). Among nonmedical staff, GI symptoms correlated with significantly lower hemoglobin levels (117 g/L [range, 106-127] vs. 133 g/L [range, 114-141], P = .03), and significantly higher levels of C-reactive protein (7.3 mg [range, 2.9-6.6] vs. 3.8 mg (1.8-5.8), P = .021) and alanine aminotransferase (64.1 U/L [range, 51.2-64.4] vs. 46.6 U/L [range, 31.9-61.2]; P = .049). Gastrointestinal symptoms also correlated significantly with fatigue, sore throat, and dizziness. Although the nonmedical cohort included five more males than females, females made up nearly two-thirds (63%) of individuals with GI symptoms (P = .03).

Although 25% of medical staff in the study had GI symptoms, GI symptoms did not correlate with other symptoms or with laboratory findings. This might be because “most of the infected medical staff were younger nurses without comorbidities,” the investigators wrote. “In addition, there [was] less delay from the onset of symptoms to hospital admission.”

For the overall cohort, the most prevalent symptoms were fever (84%), fatigue (52%), productive cough (42%), dry cough (42%), and myalgia (34%). Although these symptoms are typical of COVID-19 infection, most patients were not tested for the virus, “which will inevitably lead to several patients without [COVID-19 pneumonia] being included,” the investigators noted.

The National Nature Science Foundation of China provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhou Z et al. Gastroenterology. 2020 Mar 18. doi: 10.1053/j.gastro.2020.03.020.

Gastrointestinal symptoms affected 26% of hospital employees hospitalized with presumptive COVID-19 infection, according to the results of a study from Wuhan, China.

Among nonmedical personnel in the study (median age, 62 years), 63% of those with GI symptoms were female (P = .03), wrote Zili Zhou of Huazhong University of Science and Technology, Wuhan, China, and associates. Gastrointestinal symptoms correlated significantly with lower hemoglobin levels, increased levels of inflammatory markers, and poorer liver function, but not with clinical complications or mortality, they noted. However, “most patients were still hospitalized at the time of [manuscript] submission, [which made it] difficult to further assess the correlation between GI symptoms and clinical outcomes,” they wrote in Gastroenterology.

Reverse transcriptase polymerase chain reaction has detected COVID-19 in patients’ stool, and COVID-19’s primary receptor for cellular entry, the angiotensin converting enzyme 2 (ACE2) receptor, “is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon,” the investigators wrote. They compared laboratory and clinical findings among 254 adults with and without GI symptoms who were admitted to Wuhan’s main hospital with presumptive COVID-19 pneumonia between December 20, 2019, and February 9, 2020. All patients were employed by the hospital.

Gastrointestinal symptoms affected 26% of patients and most commonly included diarrhea (18%), nausea (8%), vomiting (6%), and abdominal pain (2%), the researchers reported. Arrhythmias and shock were rare, affecting less than 0.5% of patients. A total of 16 patients (6%) died.

The 161 nonmedical staff in the study were older and, therefore, were evaluated separately from medical staff (respective medians, 36 and 62 years; interquartile ranges, 31-41 years and 49-69 years). Among nonmedical staff, GI symptoms correlated with significantly lower hemoglobin levels (117 g/L [range, 106-127] vs. 133 g/L [range, 114-141], P = .03), and significantly higher levels of C-reactive protein (7.3 mg [range, 2.9-6.6] vs. 3.8 mg (1.8-5.8), P = .021) and alanine aminotransferase (64.1 U/L [range, 51.2-64.4] vs. 46.6 U/L [range, 31.9-61.2]; P = .049). Gastrointestinal symptoms also correlated significantly with fatigue, sore throat, and dizziness. Although the nonmedical cohort included five more males than females, females made up nearly two-thirds (63%) of individuals with GI symptoms (P = .03).

Although 25% of medical staff in the study had GI symptoms, GI symptoms did not correlate with other symptoms or with laboratory findings. This might be because “most of the infected medical staff were younger nurses without comorbidities,” the investigators wrote. “In addition, there [was] less delay from the onset of symptoms to hospital admission.”

For the overall cohort, the most prevalent symptoms were fever (84%), fatigue (52%), productive cough (42%), dry cough (42%), and myalgia (34%). Although these symptoms are typical of COVID-19 infection, most patients were not tested for the virus, “which will inevitably lead to several patients without [COVID-19 pneumonia] being included,” the investigators noted.

The National Nature Science Foundation of China provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhou Z et al. Gastroenterology. 2020 Mar 18. doi: 10.1053/j.gastro.2020.03.020.

Recognizing the presence of functional heartburn is vital to prevent unnecessary acid-suppressive therapy and invasive antireflux treatments, which are ineffective and “might even lead to harm,” cautions a new clinical practice update from the American Gastroenterological Association.

Proton pump inhibitors (PPIs) “have no therapeutic value in functional heartburn,” unless patients also have gastroesophageal reflux disease (GERD), Ronnie Fass, MD, of MetroHealth System in Cleveland, and coauthors wrote in Gastroenterology. If clinical work-up finds no clear evidence of GERD, “an attempt to discontinue PPI therapy is warranted,” they added. Likewise, antireflux surgery and endoscopic treatments for GERD “have no therapeutic benefit in functional heartburn and should not be recommended.” However, histamine₂ receptor antagonists (H₂RAs) “may have an independent benefit in functional heartburn from an esophageal pain modulatory effect.”

Heartburn consists of burning or discomfort that radiates retrosternally from the epigastrium. Patients may report reflux, regurgitation, chest pain or discomfort, fullness, water brash, belching, or a sour and bitter taste in the mouth. Functional heartburn is heartburn that persists after at least 3 months of maximal (double-dose) PPIs taken before meals. Confirming functional heartburn requires high-resolution manometry to rule out major esophageal motor disorders, esophageal endoscopy with biopsy to rule out structural abnormalities and mucosal disorders (e.g., erosive esophagitis, Barrett’s esophagus, and eosinophilic esophagitis), and either pH monitoring while off PPI therapy or pH-impedance monitoring on therapy if patients have proven GERD. According to the clinical practice update, pH studies should document physiological acid exposure in the distal esophagus that is unlinked to symptoms (i.e., both a negative symptom index and a negative symptom association probability).

Functional heartburn resembles GERD, but symptoms are unrelated to acid exposure. Balloon distension studies indicate that patients with functional heartburn experience both esophageal and rectal hypersensitivity. Anxiety and mood disorders also are highly prevalent, and patients “will likely not improve unless esophageal perception and underlying affective disorders are adequately managed,” Dr. Fass and coauthors emphasized.

In keeping with this approach, limited evidence from clinical trials supports the first-line use of neuromodulator therapies, including selective serotonin reuptake inhibitors, tricyclic antidepressants, the serotonin 4 receptor antagonist tegaserod, and H₂RAs (e.g., cimetidine, famotidine, nizatidine). The only SSRI studied thus far in functional heartburn is fluoxetine. In a placebo-controlled trial of patients with normal endoscopy and heartburn that had not responded to once-daily PPI therapy, 6 weeks of fluoxetine (20 mg daily) significantly outperformed double-dose omeprazole (P < .001) for the primary endpoint of heartburn-free days. “This superior therapeutic effect of fluoxetine was seen only in the subset of patients with a normal pH test,” the experts noted.

In another placebo-controlled trial, the neuromodulator tegaserod (a serotonin 5-HT₄ receptor partial agonist) significantly improved tolerance of esophageal pressure during balloon distension and significantly decreased heartburn, regurgitation, and associated distress among patients with functional heartburn. Melatonin, which “also has a pain modulatory effect in the gastrointestinal tract,” significantly improved symptom-related quality of life, compared with nortriptyline and placebo in a randomized, three-arm trial. The patients on melatonin received a 6-mg dose at bedtime for 3 months.

Acupuncture and hypnotherapy also have shown benefit in small studies of functional heartburn patients and may be appropriate as monotherapy or adjunctive treatment, according to the clinical practice update. In a small randomized study, 10 acupuncture sessions delivered over 4 weeks significantly improved daytime and nighttime heartburn and acid regurgitation scores, compared with double-dose PPI. “Mean general health score was significantly improved only in those receiving acupuncture,” the experts noted. Hypnotherapy, the only psychological intervention to have been studied in functional heartburn, was associated with significant improvements in symptoms, visceral anxiety, and quality of life in an uncontrolled study of nine patients.

Although the overall prevalence of functional heartburn is unclear, it has been detected in 21%-39% of PPI-refractory patients evaluated with pH-impedance monitoring, Dr. Fass and associates wrote. Because functional heartburn and GERD can co-occur, some patients with functional heartburn may develop long-term complications of GERD, such as Barrett’s esophagus or peptic stricture. However, the experts noted, “this is anticipated to be rare, and the vast majority of patients with functional heartburn will have compromised quality of life, rather than organic complications over time.

Dr. Fass reported receiving consulting, research, and speaking fees from Ironwood, Takeda, and Salix, among other pharmaceutical companies; Dr. Zerbib received consulting fees from Reckitt Benckiser; and Dr. Gyawali received teaching and consulting fees from Medtronic, Diversatek, and Ironwood.

SOURCE: Fass R et al. Gastroenterology. 2020 Feb 1. doi: 10.1053/j.gastro.2020.01.034.

This story was updated on 6/11/2020.

Recognizing the presence of functional heartburn is vital to prevent unnecessary acid-suppressive therapy and invasive antireflux treatments, which are ineffective and “might even lead to harm,” cautions a new clinical practice update from the American Gastroenterological Association.

Proton pump inhibitors (PPIs) “have no therapeutic value in functional heartburn,” unless patients also have gastroesophageal reflux disease (GERD), Ronnie Fass, MD, of MetroHealth System in Cleveland, and coauthors wrote in Gastroenterology. If clinical work-up finds no clear evidence of GERD, “an attempt to discontinue PPI therapy is warranted,” they added. Likewise, antireflux surgery and endoscopic treatments for GERD “have no therapeutic benefit in functional heartburn and should not be recommended.” However, histamine₂ receptor antagonists (H₂RAs) “may have an independent benefit in functional heartburn from an esophageal pain modulatory effect.”

Heartburn consists of burning or discomfort that radiates retrosternally from the epigastrium. Patients may report reflux, regurgitation, chest pain or discomfort, fullness, water brash, belching, or a sour and bitter taste in the mouth. Functional heartburn is heartburn that persists after at least 3 months of maximal (double-dose) PPIs taken before meals. Confirming functional heartburn requires high-resolution manometry to rule out major esophageal motor disorders, esophageal endoscopy with biopsy to rule out structural abnormalities and mucosal disorders (e.g., erosive esophagitis, Barrett’s esophagus, and eosinophilic esophagitis), and either pH monitoring while off PPI therapy or pH-impedance monitoring on therapy if patients have proven GERD. According to the clinical practice update, pH studies should document physiological acid exposure in the distal esophagus that is unlinked to symptoms (i.e., both a negative symptom index and a negative symptom association probability).

Functional heartburn resembles GERD, but symptoms are unrelated to acid exposure. Balloon distension studies indicate that patients with functional heartburn experience both esophageal and rectal hypersensitivity. Anxiety and mood disorders also are highly prevalent, and patients “will likely not improve unless esophageal perception and underlying affective disorders are adequately managed,” Dr. Fass and coauthors emphasized.

In keeping with this approach, limited evidence from clinical trials supports the first-line use of neuromodulator therapies, including selective serotonin reuptake inhibitors, tricyclic antidepressants, the serotonin 4 receptor antagonist tegaserod, and H₂RAs (e.g., cimetidine, famotidine, nizatidine). The only SSRI studied thus far in functional heartburn is fluoxetine. In a placebo-controlled trial of patients with normal endoscopy and heartburn that had not responded to once-daily PPI therapy, 6 weeks of fluoxetine (20 mg daily) significantly outperformed double-dose omeprazole (P < .001) for the primary endpoint of heartburn-free days. “This superior therapeutic effect of fluoxetine was seen only in the subset of patients with a normal pH test,” the experts noted.

In another placebo-controlled trial, the neuromodulator tegaserod (a serotonin 5-HT₄ receptor partial agonist) significantly improved tolerance of esophageal pressure during balloon distension and significantly decreased heartburn, regurgitation, and associated distress among patients with functional heartburn. Melatonin, which “also has a pain modulatory effect in the gastrointestinal tract,” significantly improved symptom-related quality of life, compared with nortriptyline and placebo in a randomized, three-arm trial. The patients on melatonin received a 6-mg dose at bedtime for 3 months.

Acupuncture and hypnotherapy also have shown benefit in small studies of functional heartburn patients and may be appropriate as monotherapy or adjunctive treatment, according to the clinical practice update. In a small randomized study, 10 acupuncture sessions delivered over 4 weeks significantly improved daytime and nighttime heartburn and acid regurgitation scores, compared with double-dose PPI. “Mean general health score was significantly improved only in those receiving acupuncture,” the experts noted. Hypnotherapy, the only psychological intervention to have been studied in functional heartburn, was associated with significant improvements in symptoms, visceral anxiety, and quality of life in an uncontrolled study of nine patients.

Although the overall prevalence of functional heartburn is unclear, it has been detected in 21%-39% of PPI-refractory patients evaluated with pH-impedance monitoring, Dr. Fass and associates wrote. Because functional heartburn and GERD can co-occur, some patients with functional heartburn may develop long-term complications of GERD, such as Barrett’s esophagus or peptic stricture. However, the experts noted, “this is anticipated to be rare, and the vast majority of patients with functional heartburn will have compromised quality of life, rather than organic complications over time.

Dr. Fass reported receiving consulting, research, and speaking fees from Ironwood, Takeda, and Salix, among other pharmaceutical companies; Dr. Zerbib received consulting fees from Reckitt Benckiser; and Dr. Gyawali received teaching and consulting fees from Medtronic, Diversatek, and Ironwood.

SOURCE: Fass R et al. Gastroenterology. 2020 Feb 1. doi: 10.1053/j.gastro.2020.01.034.

This story was updated on 6/11/2020.

Recognizing the presence of functional heartburn is vital to prevent unnecessary acid-suppressive therapy and invasive antireflux treatments, which are ineffective and “might even lead to harm,” cautions a new clinical practice update from the American Gastroenterological Association.

Proton pump inhibitors (PPIs) “have no therapeutic value in functional heartburn,” unless patients also have gastroesophageal reflux disease (GERD), Ronnie Fass, MD, of MetroHealth System in Cleveland, and coauthors wrote in Gastroenterology. If clinical work-up finds no clear evidence of GERD, “an attempt to discontinue PPI therapy is warranted,” they added. Likewise, antireflux surgery and endoscopic treatments for GERD “have no therapeutic benefit in functional heartburn and should not be recommended.” However, histamine₂ receptor antagonists (H₂RAs) “may have an independent benefit in functional heartburn from an esophageal pain modulatory effect.”

Heartburn consists of burning or discomfort that radiates retrosternally from the epigastrium. Patients may report reflux, regurgitation, chest pain or discomfort, fullness, water brash, belching, or a sour and bitter taste in the mouth. Functional heartburn is heartburn that persists after at least 3 months of maximal (double-dose) PPIs taken before meals. Confirming functional heartburn requires high-resolution manometry to rule out major esophageal motor disorders, esophageal endoscopy with biopsy to rule out structural abnormalities and mucosal disorders (e.g., erosive esophagitis, Barrett’s esophagus, and eosinophilic esophagitis), and either pH monitoring while off PPI therapy or pH-impedance monitoring on therapy if patients have proven GERD. According to the clinical practice update, pH studies should document physiological acid exposure in the distal esophagus that is unlinked to symptoms (i.e., both a negative symptom index and a negative symptom association probability).

Functional heartburn resembles GERD, but symptoms are unrelated to acid exposure. Balloon distension studies indicate that patients with functional heartburn experience both esophageal and rectal hypersensitivity. Anxiety and mood disorders also are highly prevalent, and patients “will likely not improve unless esophageal perception and underlying affective disorders are adequately managed,” Dr. Fass and coauthors emphasized.

In keeping with this approach, limited evidence from clinical trials supports the first-line use of neuromodulator therapies, including selective serotonin reuptake inhibitors, tricyclic antidepressants, the serotonin 4 receptor antagonist tegaserod, and H₂RAs (e.g., cimetidine, famotidine, nizatidine). The only SSRI studied thus far in functional heartburn is fluoxetine. In a placebo-controlled trial of patients with normal endoscopy and heartburn that had not responded to once-daily PPI therapy, 6 weeks of fluoxetine (20 mg daily) significantly outperformed double-dose omeprazole (P < .001) for the primary endpoint of heartburn-free days. “This superior therapeutic effect of fluoxetine was seen only in the subset of patients with a normal pH test,” the experts noted.

In another placebo-controlled trial, the neuromodulator tegaserod (a serotonin 5-HT₄ receptor partial agonist) significantly improved tolerance of esophageal pressure during balloon distension and significantly decreased heartburn, regurgitation, and associated distress among patients with functional heartburn. Melatonin, which “also has a pain modulatory effect in the gastrointestinal tract,” significantly improved symptom-related quality of life, compared with nortriptyline and placebo in a randomized, three-arm trial. The patients on melatonin received a 6-mg dose at bedtime for 3 months.

Acupuncture and hypnotherapy also have shown benefit in small studies of functional heartburn patients and may be appropriate as monotherapy or adjunctive treatment, according to the clinical practice update. In a small randomized study, 10 acupuncture sessions delivered over 4 weeks significantly improved daytime and nighttime heartburn and acid regurgitation scores, compared with double-dose PPI. “Mean general health score was significantly improved only in those receiving acupuncture,” the experts noted. Hypnotherapy, the only psychological intervention to have been studied in functional heartburn, was associated with significant improvements in symptoms, visceral anxiety, and quality of life in an uncontrolled study of nine patients.

Although the overall prevalence of functional heartburn is unclear, it has been detected in 21%-39% of PPI-refractory patients evaluated with pH-impedance monitoring, Dr. Fass and associates wrote. Because functional heartburn and GERD can co-occur, some patients with functional heartburn may develop long-term complications of GERD, such as Barrett’s esophagus or peptic stricture. However, the experts noted, “this is anticipated to be rare, and the vast majority of patients with functional heartburn will have compromised quality of life, rather than organic complications over time.

Dr. Fass reported receiving consulting, research, and speaking fees from Ironwood, Takeda, and Salix, among other pharmaceutical companies; Dr. Zerbib received consulting fees from Reckitt Benckiser; and Dr. Gyawali received teaching and consulting fees from Medtronic, Diversatek, and Ironwood.

SOURCE: Fass R et al. Gastroenterology. 2020 Feb 1. doi: 10.1053/j.gastro.2020.01.034.

This story was updated on 6/11/2020.

For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.

The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.

Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.

Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.

Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.

Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.

The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”

Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
 

SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.

For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.

The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.

Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.

Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.

Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.

Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.

The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”

Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
 

SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.

For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.

The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.

Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.

Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.

Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.

Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.

The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”

Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
 

SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.

Total underwater colonoscopy can surmount challenges with insertion, simplify endoscopic mucosal resection, and lessen pain and the need for sedation, according to a “Here and Now: Clinical Practice” article published in Clinical Gastroenterology and Hepatology.

At the same time, total underwater colonoscopy has not been shown to significantly affect adenoma miss rates, requires a longer insertion and overall procedure time, and cannot be performed without adequate bowel preparation, wrote Joseph C. Anderson, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and the Geisel School of Medicine at Dartmouth, Hanover, N.H.

He noted that total underwater colonoscopy is not the same as water immersion or water exchange, both of which involve infusing water while inserting the colonoscope and then distending the colon with carbon dioxide to visualize the mucosa during withdrawal. During total underwater colonoscopy, insertion, examination, and resection all are carried out with the lumen filled with water. Air is suctioned out, and the air valve is kept off.

This approach can surmount problems with insertion stemming from either severe angulation (often of the sigmoid colon), or redundant colon (excessive looping) that does not respond to abdominal pressure, colonoscope stiffening, or a change in position, Dr. Anderson noted. He explained that, unlike air, water does not maximally distend the lumen and therefore does not exacerbate angulation. “When I am in the ascending colon and cannot reach the cecum, I turn off the air valve, aspirate all gas, infuse water, and complete the insertion underwater,” he said. “Another advantage of water in patients with angulated sigmoid colons is that its use could prevent [the] excessive use of air and potential barotrauma of the cecum, even when using carbon dioxide.”

The use of water can aid endoscopic mucosal resection (EMR) because polyps tend to float into view (including from hard-to-visualize areas, such as folds) and into the snare, he said. “Because water has a magnifying property, underwater EMR may allow for easier delineation of the polyp’s border, also facilitating complete removal.”

Nonetheless, it remains unclear whether the use of total underwater colonoscopy significantly affects adenoma detection rates. In a recent study, Dr. Anderson and his coinvestiators randomly assigned 121 patients to undergo either colonoscopy with carbon dioxide insufflation, followed by total underwater colonoscopy, or the same examinations in the reverse sequence (Anderson KC et al. Gastrointest Endosc. 2019;89:591-8). Adenoma miss rates were statistically similar between groups. Although water decreases green mucus and residual stool and suspends “unsuctionable” particles (e.g. seeds) into the cecal lumen, where colonoscopists can better see past them, water also increases the production of white mucus, which can be difficult to remove during withdrawal, Dr. Anderson said.

He cited meta-analyses in which colonoscopies performed with water, without sedation or with minimal sedation, were associated with less pain and a higher likelihood of performing a complete examination than when only air was used. “I find this [approach] particularly useful in older, thinner patients, especially women,” Dr. Anderson said. “In addition, in patients with multiple comorbidities, cecal intubation often can be achieved safely with minimal sedation.”

Dr. Anderson reported having no relevant conflicts of interest.

SOURCE: Anderson JC. Clin Gastroenterol Hepatol. 2020 Feb 25. doi: 10.1016/j.cgh.2020.02.042.

Total underwater colonoscopy can surmount challenges with insertion, simplify endoscopic mucosal resection, and lessen pain and the need for sedation, according to a “Here and Now: Clinical Practice” article published in Clinical Gastroenterology and Hepatology.

At the same time, total underwater colonoscopy has not been shown to significantly affect adenoma miss rates, requires a longer insertion and overall procedure time, and cannot be performed without adequate bowel preparation, wrote Joseph C. Anderson, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and the Geisel School of Medicine at Dartmouth, Hanover, N.H.

He noted that total underwater colonoscopy is not the same as water immersion or water exchange, both of which involve infusing water while inserting the colonoscope and then distending the colon with carbon dioxide to visualize the mucosa during withdrawal. During total underwater colonoscopy, insertion, examination, and resection all are carried out with the lumen filled with water. Air is suctioned out, and the air valve is kept off.

This approach can surmount problems with insertion stemming from either severe angulation (often of the sigmoid colon), or redundant colon (excessive looping) that does not respond to abdominal pressure, colonoscope stiffening, or a change in position, Dr. Anderson noted. He explained that, unlike air, water does not maximally distend the lumen and therefore does not exacerbate angulation. “When I am in the ascending colon and cannot reach the cecum, I turn off the air valve, aspirate all gas, infuse water, and complete the insertion underwater,” he said. “Another advantage of water in patients with angulated sigmoid colons is that its use could prevent [the] excessive use of air and potential barotrauma of the cecum, even when using carbon dioxide.”

The use of water can aid endoscopic mucosal resection (EMR) because polyps tend to float into view (including from hard-to-visualize areas, such as folds) and into the snare, he said. “Because water has a magnifying property, underwater EMR may allow for easier delineation of the polyp’s border, also facilitating complete removal.”

Nonetheless, it remains unclear whether the use of total underwater colonoscopy significantly affects adenoma detection rates. In a recent study, Dr. Anderson and his coinvestiators randomly assigned 121 patients to undergo either colonoscopy with carbon dioxide insufflation, followed by total underwater colonoscopy, or the same examinations in the reverse sequence (Anderson KC et al. Gastrointest Endosc. 2019;89:591-8). Adenoma miss rates were statistically similar between groups. Although water decreases green mucus and residual stool and suspends “unsuctionable” particles (e.g. seeds) into the cecal lumen, where colonoscopists can better see past them, water also increases the production of white mucus, which can be difficult to remove during withdrawal, Dr. Anderson said.

He cited meta-analyses in which colonoscopies performed with water, without sedation or with minimal sedation, were associated with less pain and a higher likelihood of performing a complete examination than when only air was used. “I find this [approach] particularly useful in older, thinner patients, especially women,” Dr. Anderson said. “In addition, in patients with multiple comorbidities, cecal intubation often can be achieved safely with minimal sedation.”

Dr. Anderson reported having no relevant conflicts of interest.

SOURCE: Anderson JC. Clin Gastroenterol Hepatol. 2020 Feb 25. doi: 10.1016/j.cgh.2020.02.042.

Total underwater colonoscopy can surmount challenges with insertion, simplify endoscopic mucosal resection, and lessen pain and the need for sedation, according to a “Here and Now: Clinical Practice” article published in Clinical Gastroenterology and Hepatology.

At the same time, total underwater colonoscopy has not been shown to significantly affect adenoma miss rates, requires a longer insertion and overall procedure time, and cannot be performed without adequate bowel preparation, wrote Joseph C. Anderson, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and the Geisel School of Medicine at Dartmouth, Hanover, N.H.

He noted that total underwater colonoscopy is not the same as water immersion or water exchange, both of which involve infusing water while inserting the colonoscope and then distending the colon with carbon dioxide to visualize the mucosa during withdrawal. During total underwater colonoscopy, insertion, examination, and resection all are carried out with the lumen filled with water. Air is suctioned out, and the air valve is kept off.

This approach can surmount problems with insertion stemming from either severe angulation (often of the sigmoid colon), or redundant colon (excessive looping) that does not respond to abdominal pressure, colonoscope stiffening, or a change in position, Dr. Anderson noted. He explained that, unlike air, water does not maximally distend the lumen and therefore does not exacerbate angulation. “When I am in the ascending colon and cannot reach the cecum, I turn off the air valve, aspirate all gas, infuse water, and complete the insertion underwater,” he said. “Another advantage of water in patients with angulated sigmoid colons is that its use could prevent [the] excessive use of air and potential barotrauma of the cecum, even when using carbon dioxide.”

The use of water can aid endoscopic mucosal resection (EMR) because polyps tend to float into view (including from hard-to-visualize areas, such as folds) and into the snare, he said. “Because water has a magnifying property, underwater EMR may allow for easier delineation of the polyp’s border, also facilitating complete removal.”

Nonetheless, it remains unclear whether the use of total underwater colonoscopy significantly affects adenoma detection rates. In a recent study, Dr. Anderson and his coinvestiators randomly assigned 121 patients to undergo either colonoscopy with carbon dioxide insufflation, followed by total underwater colonoscopy, or the same examinations in the reverse sequence (Anderson KC et al. Gastrointest Endosc. 2019;89:591-8). Adenoma miss rates were statistically similar between groups. Although water decreases green mucus and residual stool and suspends “unsuctionable” particles (e.g. seeds) into the cecal lumen, where colonoscopists can better see past them, water also increases the production of white mucus, which can be difficult to remove during withdrawal, Dr. Anderson said.

He cited meta-analyses in which colonoscopies performed with water, without sedation or with minimal sedation, were associated with less pain and a higher likelihood of performing a complete examination than when only air was used. “I find this [approach] particularly useful in older, thinner patients, especially women,” Dr. Anderson said. “In addition, in patients with multiple comorbidities, cecal intubation often can be achieved safely with minimal sedation.”

Dr. Anderson reported having no relevant conflicts of interest.

SOURCE: Anderson JC. Clin Gastroenterol Hepatol. 2020 Feb 25. doi: 10.1016/j.cgh.2020.02.042.

The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.

The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.

Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.

Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.

“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”

They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.

The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.

The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.

The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.

Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.

Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.

“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”

They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.

The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.

The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.

The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.

Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.

Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.

“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”

They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.

The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.

Patients with eosinophilic esophagitis should receive topical steroids instead of oral steroids or no treatment, according to new recommendations from the American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters.

In a pooled analysis of eight double-blind clinical trials, monotherapy with topical budesonide or topical fluticasone was about 61% more likely than placebo to produce histologic remissions in patients with eosinophilic esophagitis (relative risk of failure to achieve remission, 0.39; 95% confidence interval, 0.26-0.58), wrote Ikuo Hirano, MD, of Northwestern University, Chicago. Although these trials differed methodologically, the results were robust enough to warrant a strong recommendation for topical steroids, wrote Dr. Hirano and coauthors of the guidelines, published in Gastroenterology (doi: 10.1053/j.gastro.2020.02.038). “[T]he same inhaled steroid agents are considered very safe for use in children and adults with asthma and are routinely used in [its] primary management,” they noted.

All other recommendations in the guidelines are graded as conditional, reflecting a lack of high-quality supporting evidence. For example, one only study to date has compared topical and oral steroids for patients with eosinophilic esophagitis. In this pediatric trial, children benefited similarly from fluticasone (two puffs four times daily) and oral prednisone (1 mg/kg twice daily), but prednisone caused side effects (weight gain and cushingoid appearance) in 40% of patients, while topical steroids caused oral candidiasis (thrush) in only 15% of patients. Similarities between pediatric and adult eosinophilic esophagitis support the use of topical versus oral steroids in both groups, the guidelines conclude.

Eosinophilic esophagitis tends to be chronic and can progress to recurrent dysphagia, esophageal impactions, and stricture if left untreated. For this reason, the guidelines call for remitted patients to stay on topical steroids as maintenance therapy despite “very low confidence in the estimated benefits of [any type of] long-term therapy.” In a very small trial, 1 year of low-dose budesonide maintenance therapy (0.25 mg twice daily) outperformed placebo, but only 36% of patients maintained less than 5 eosinophils per high power field. Other studies have produced mixed results. Pending more data, the guidelines call maintenance treatment with topical steroids, proton pump inhibitors, and elimination diets “reasonable options” that comprise “a preference-sensitive area of management.”

Dietary interventions for eosinophilic esophagitis include the elemental diet (amino acid–based formulas), the empiric six-food elimination diet, and eliminating foods based on allergy testing. The guidelines cite moderate-quality evidence for the elemental diet, which induced histologic remissions (less than than 15 eosinophils per high power field) in nearly 94% of patients in six single-arm observational studies (in contrast, the rate of histologic failure with placebo is nearly 87%). However, patients may struggle to adhere to both the elemental diet and the six-food elimination diet, which has less supporting evidence. Hence, patients “may reasonably decline” these treatment options and “may prefer alternative medical or dietary therapies” to a diet exclusively based on food allergens, tests for which are potentially inaccurate, the guidelines state.

Esophageal dilation is recommended for patients with stricture based on a systematic review in which 87% of patients improved with this therapy. However, dilation “does not address the esophageal inflammation associated with eosinophilic esophagitis,” and the “assumption that no clinical improvement would occur if dilation was not performed likely overestimates [its] treatment benefit, given the reported symptom-placebo response noted in controlled trials,” according to the guidelines. Moreover, the evidence for dilation “was considered low quality due to the retrospective, single-arm design of all but one of the reports, and the lack of a standard definition for what constitutes clinical improvement.”

Anti-IgE therapy is not recommended – it failed to improve symptoms or esophageal eosinophilia in the only trial conducted to date. Because of a lack of evidence, the guidelines state that patients should receive only montelukast, cromolyn sodium, immunomodulators, anti–tumor necrosis factor (anti-TNF) therapies, or therapies targeting interleukin (IL)-5, IL-13, or IL-4 in the context of a clinical trial.

Eosinophilic esophagitis is triggered by exposure to food antigens and often overlaps with other atopic conditions, such as asthma, eczema, and allergic rhinitis. It has no approved treatments in the United States, although in 2018, the European Medicines Agency approved a budesonide tablet formulation.

The guideline authors disclosed no conflicts of interest.

SOURCE: Hirano I et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.02.038.

Patients with eosinophilic esophagitis should receive topical steroids instead of oral steroids or no treatment, according to new recommendations from the American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters.

In a pooled analysis of eight double-blind clinical trials, monotherapy with topical budesonide or topical fluticasone was about 61% more likely than placebo to produce histologic remissions in patients with eosinophilic esophagitis (relative risk of failure to achieve remission, 0.39; 95% confidence interval, 0.26-0.58), wrote Ikuo Hirano, MD, of Northwestern University, Chicago. Although these trials differed methodologically, the results were robust enough to warrant a strong recommendation for topical steroids, wrote Dr. Hirano and coauthors of the guidelines, published in Gastroenterology (doi: 10.1053/j.gastro.2020.02.038). “[T]he same inhaled steroid agents are considered very safe for use in children and adults with asthma and are routinely used in [its] primary management,” they noted.

All other recommendations in the guidelines are graded as conditional, reflecting a lack of high-quality supporting evidence. For example, one only study to date has compared topical and oral steroids for patients with eosinophilic esophagitis. In this pediatric trial, children benefited similarly from fluticasone (two puffs four times daily) and oral prednisone (1 mg/kg twice daily), but prednisone caused side effects (weight gain and cushingoid appearance) in 40% of patients, while topical steroids caused oral candidiasis (thrush) in only 15% of patients. Similarities between pediatric and adult eosinophilic esophagitis support the use of topical versus oral steroids in both groups, the guidelines conclude.

Eosinophilic esophagitis tends to be chronic and can progress to recurrent dysphagia, esophageal impactions, and stricture if left untreated. For this reason, the guidelines call for remitted patients to stay on topical steroids as maintenance therapy despite “very low confidence in the estimated benefits of [any type of] long-term therapy.” In a very small trial, 1 year of low-dose budesonide maintenance therapy (0.25 mg twice daily) outperformed placebo, but only 36% of patients maintained less than 5 eosinophils per high power field. Other studies have produced mixed results. Pending more data, the guidelines call maintenance treatment with topical steroids, proton pump inhibitors, and elimination diets “reasonable options” that comprise “a preference-sensitive area of management.”

Dietary interventions for eosinophilic esophagitis include the elemental diet (amino acid–based formulas), the empiric six-food elimination diet, and eliminating foods based on allergy testing. The guidelines cite moderate-quality evidence for the elemental diet, which induced histologic remissions (less than than 15 eosinophils per high power field) in nearly 94% of patients in six single-arm observational studies (in contrast, the rate of histologic failure with placebo is nearly 87%). However, patients may struggle to adhere to both the elemental diet and the six-food elimination diet, which has less supporting evidence. Hence, patients “may reasonably decline” these treatment options and “may prefer alternative medical or dietary therapies” to a diet exclusively based on food allergens, tests for which are potentially inaccurate, the guidelines state.

Esophageal dilation is recommended for patients with stricture based on a systematic review in which 87% of patients improved with this therapy. However, dilation “does not address the esophageal inflammation associated with eosinophilic esophagitis,” and the “assumption that no clinical improvement would occur if dilation was not performed likely overestimates [its] treatment benefit, given the reported symptom-placebo response noted in controlled trials,” according to the guidelines. Moreover, the evidence for dilation “was considered low quality due to the retrospective, single-arm design of all but one of the reports, and the lack of a standard definition for what constitutes clinical improvement.”

Anti-IgE therapy is not recommended – it failed to improve symptoms or esophageal eosinophilia in the only trial conducted to date. Because of a lack of evidence, the guidelines state that patients should receive only montelukast, cromolyn sodium, immunomodulators, anti–tumor necrosis factor (anti-TNF) therapies, or therapies targeting interleukin (IL)-5, IL-13, or IL-4 in the context of a clinical trial.

Eosinophilic esophagitis is triggered by exposure to food antigens and often overlaps with other atopic conditions, such as asthma, eczema, and allergic rhinitis. It has no approved treatments in the United States, although in 2018, the European Medicines Agency approved a budesonide tablet formulation.

The guideline authors disclosed no conflicts of interest.

SOURCE: Hirano I et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.02.038.

Patients with eosinophilic esophagitis should receive topical steroids instead of oral steroids or no treatment, according to new recommendations from the American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters.

In a pooled analysis of eight double-blind clinical trials, monotherapy with topical budesonide or topical fluticasone was about 61% more likely than placebo to produce histologic remissions in patients with eosinophilic esophagitis (relative risk of failure to achieve remission, 0.39; 95% confidence interval, 0.26-0.58), wrote Ikuo Hirano, MD, of Northwestern University, Chicago. Although these trials differed methodologically, the results were robust enough to warrant a strong recommendation for topical steroids, wrote Dr. Hirano and coauthors of the guidelines, published in Gastroenterology (doi: 10.1053/j.gastro.2020.02.038). “[T]he same inhaled steroid agents are considered very safe for use in children and adults with asthma and are routinely used in [its] primary management,” they noted.

All other recommendations in the guidelines are graded as conditional, reflecting a lack of high-quality supporting evidence. For example, one only study to date has compared topical and oral steroids for patients with eosinophilic esophagitis. In this pediatric trial, children benefited similarly from fluticasone (two puffs four times daily) and oral prednisone (1 mg/kg twice daily), but prednisone caused side effects (weight gain and cushingoid appearance) in 40% of patients, while topical steroids caused oral candidiasis (thrush) in only 15% of patients. Similarities between pediatric and adult eosinophilic esophagitis support the use of topical versus oral steroids in both groups, the guidelines conclude.

Eosinophilic esophagitis tends to be chronic and can progress to recurrent dysphagia, esophageal impactions, and stricture if left untreated. For this reason, the guidelines call for remitted patients to stay on topical steroids as maintenance therapy despite “very low confidence in the estimated benefits of [any type of] long-term therapy.” In a very small trial, 1 year of low-dose budesonide maintenance therapy (0.25 mg twice daily) outperformed placebo, but only 36% of patients maintained less than 5 eosinophils per high power field. Other studies have produced mixed results. Pending more data, the guidelines call maintenance treatment with topical steroids, proton pump inhibitors, and elimination diets “reasonable options” that comprise “a preference-sensitive area of management.”

Dietary interventions for eosinophilic esophagitis include the elemental diet (amino acid–based formulas), the empiric six-food elimination diet, and eliminating foods based on allergy testing. The guidelines cite moderate-quality evidence for the elemental diet, which induced histologic remissions (less than than 15 eosinophils per high power field) in nearly 94% of patients in six single-arm observational studies (in contrast, the rate of histologic failure with placebo is nearly 87%). However, patients may struggle to adhere to both the elemental diet and the six-food elimination diet, which has less supporting evidence. Hence, patients “may reasonably decline” these treatment options and “may prefer alternative medical or dietary therapies” to a diet exclusively based on food allergens, tests for which are potentially inaccurate, the guidelines state.

Esophageal dilation is recommended for patients with stricture based on a systematic review in which 87% of patients improved with this therapy. However, dilation “does not address the esophageal inflammation associated with eosinophilic esophagitis,” and the “assumption that no clinical improvement would occur if dilation was not performed likely overestimates [its] treatment benefit, given the reported symptom-placebo response noted in controlled trials,” according to the guidelines. Moreover, the evidence for dilation “was considered low quality due to the retrospective, single-arm design of all but one of the reports, and the lack of a standard definition for what constitutes clinical improvement.”

Anti-IgE therapy is not recommended – it failed to improve symptoms or esophageal eosinophilia in the only trial conducted to date. Because of a lack of evidence, the guidelines state that patients should receive only montelukast, cromolyn sodium, immunomodulators, anti–tumor necrosis factor (anti-TNF) therapies, or therapies targeting interleukin (IL)-5, IL-13, or IL-4 in the context of a clinical trial.

Eosinophilic esophagitis is triggered by exposure to food antigens and often overlaps with other atopic conditions, such as asthma, eczema, and allergic rhinitis. It has no approved treatments in the United States, although in 2018, the European Medicines Agency approved a budesonide tablet formulation.

The guideline authors disclosed no conflicts of interest.

SOURCE: Hirano I et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.02.038.