Hepatology

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

Two-fifths of adolescents and young adults in the United States may have nonalcoholic fatty liver disease (NAFLD), many with significant or advanced fibrosis, results of a nationwide surveillance study suggest.

In addition, among those who drink alcohol in excess, slightly more than half may have alcohol-associated fatty liver disease (ALD) that may lead to moderate to severe fibrosis in a substantial proportion, said Naim Alkhouri, MD, from Arizona Liver Health, Peoria, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Efforts should focus on increasing awareness of the burden of ALD and NAFLD in this population and [mitigating] modifiable risk factors to prevent disease development and disease progression to potentially advanced fibrosis and cirrhosis,” he said.
 

Liver stiffness measured

Unlike previous studies that relied on liver enzyme levels or ultrasonography to estimate the prevalence of fatty liver disease among adolescents and young adults in the United States, Dr. Alkhouri and colleagues used valid liver ultrasonographic elastography (FibroScan) measurements, recorded during 2017-2018, from the National Health and Nutrition Examination Survey (NHANES) database.

The sample included participants aged 15 to 39 years. Those with viral hepatitis, alanine aminotransferase (ALT) levels greater than 500 U/L, or pregnancy were excluded.

The investigators divided the participants into those with excessive alcohol consumption, defined using the NHANES Alcohol Use Questionnaire as having more than two drinks per day for males or more than one drink per day for females, and those with no excessive alcohol consumption.

The authors used controlled attenuation parameters to identify participants with suspected ALD or NAFLD.

They then used liver stiffness measurement cutoffs of greater than or equal to 7.5 kPa to identify moderate fibrosis and greater than or equal to 9.5 kPa to identify severe fibrosis in those with evidence of ALD and cutoffs of greater than or equal to 6.1 kPa and greater than or equal to 7.1 kPa, respectively, in those with suspected NAFLD.

The cutoffs were chosen to maximize sensitivity, as determined from published literature, Dr. Alkhouri said.
 

Uncovering a high prevalence of ALD and NAFLD

The final sample comprised 1,319 participants, including 100 with excessive alcohol use and 1,219 without.

The heavy drinkers were significantly more likely to be older, male, White, current smokers, have lower platelet counts, higher aspartate aminotransferase (AST) and ALT levels, and higher mean corpuscular volumes.

Among the excessive drinkers, 52% had ALD. Of this group, 87.7% had either no or mild fibrosis, and 12.3% had moderate to severe fibrosis.

Among patients with excessive alcohol consumption, significant predictors of ALD included male sex, higher body mass index, ALT greater than the upper limit of normal, and higher A1c percentage.

Among those who were moderate drinkers or abstemious, 40% had NAFLD. Of this subgroup, 68.9% had no or mild fibrosis, and 31.1% had moderate to severe fibrosis.

Predictors of NAFLD in this group included older age, male sex, higher body mass index, and elevated ALT, AST, albumin, platelet counts, and A1c.
 

Is drinking underreported?

In a question-and-answer session following the presentation, co-moderator Miriam B. Vos, MD, a pediatric hepatologist at Children’s Healthcare of Atlanta, asked Dr. Alkhouri about his confidence in the accuracy of the measurements of alcohol consumption and whether there could be significant overlap between the ALD and NAFLD populations.

Dr. Alkhouri noted that he and his colleagues relied on items 121 and 130 of the NHANES Alcohol Use Questionnaire, which are self-reported by participants.

“Obviously, we’re not going to get honest answers all the time,” he said. “We’ve seen even in NASH [nonalcoholic steatohepatitis] clinical trials that when patients say they do not drink any alcohol, if you actually look for alcohol metabolites, up to 20% may have some evidence of alcohol consumption.

“I’m sure there’s a lot of overlap, but there’s no formal assessment,” he added.

Dr. Alkhouri noted that among the cohort with ALD, obesity and increased A1c were prevalent, “so it goes both ways. I think NAFLD can also contribute to progression of ALD, and that’s why we need to study another entity called ‘both alcoholic and nonalcoholic fatty liver disease.’”

Dr. Vos suggested that biomarkers may be useful for detecting alcohol use among patients with NAFLD and for further study of the progression of NAFLD to ALD.

No source of funding for the study has been disclosed. Dr. Alkhouri and Dr. Vos reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two-fifths of adolescents and young adults in the United States may have nonalcoholic fatty liver disease (NAFLD), many with significant or advanced fibrosis, results of a nationwide surveillance study suggest.

In addition, among those who drink alcohol in excess, slightly more than half may have alcohol-associated fatty liver disease (ALD) that may lead to moderate to severe fibrosis in a substantial proportion, said Naim Alkhouri, MD, from Arizona Liver Health, Peoria, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Efforts should focus on increasing awareness of the burden of ALD and NAFLD in this population and [mitigating] modifiable risk factors to prevent disease development and disease progression to potentially advanced fibrosis and cirrhosis,” he said.
 

Liver stiffness measured

Unlike previous studies that relied on liver enzyme levels or ultrasonography to estimate the prevalence of fatty liver disease among adolescents and young adults in the United States, Dr. Alkhouri and colleagues used valid liver ultrasonographic elastography (FibroScan) measurements, recorded during 2017-2018, from the National Health and Nutrition Examination Survey (NHANES) database.

The sample included participants aged 15 to 39 years. Those with viral hepatitis, alanine aminotransferase (ALT) levels greater than 500 U/L, or pregnancy were excluded.

The investigators divided the participants into those with excessive alcohol consumption, defined using the NHANES Alcohol Use Questionnaire as having more than two drinks per day for males or more than one drink per day for females, and those with no excessive alcohol consumption.

The authors used controlled attenuation parameters to identify participants with suspected ALD or NAFLD.

They then used liver stiffness measurement cutoffs of greater than or equal to 7.5 kPa to identify moderate fibrosis and greater than or equal to 9.5 kPa to identify severe fibrosis in those with evidence of ALD and cutoffs of greater than or equal to 6.1 kPa and greater than or equal to 7.1 kPa, respectively, in those with suspected NAFLD.

The cutoffs were chosen to maximize sensitivity, as determined from published literature, Dr. Alkhouri said.
 

Uncovering a high prevalence of ALD and NAFLD

The final sample comprised 1,319 participants, including 100 with excessive alcohol use and 1,219 without.

The heavy drinkers were significantly more likely to be older, male, White, current smokers, have lower platelet counts, higher aspartate aminotransferase (AST) and ALT levels, and higher mean corpuscular volumes.

Among the excessive drinkers, 52% had ALD. Of this group, 87.7% had either no or mild fibrosis, and 12.3% had moderate to severe fibrosis.

Among patients with excessive alcohol consumption, significant predictors of ALD included male sex, higher body mass index, ALT greater than the upper limit of normal, and higher A1c percentage.

Among those who were moderate drinkers or abstemious, 40% had NAFLD. Of this subgroup, 68.9% had no or mild fibrosis, and 31.1% had moderate to severe fibrosis.

Predictors of NAFLD in this group included older age, male sex, higher body mass index, and elevated ALT, AST, albumin, platelet counts, and A1c.
 

Is drinking underreported?

In a question-and-answer session following the presentation, co-moderator Miriam B. Vos, MD, a pediatric hepatologist at Children’s Healthcare of Atlanta, asked Dr. Alkhouri about his confidence in the accuracy of the measurements of alcohol consumption and whether there could be significant overlap between the ALD and NAFLD populations.

Dr. Alkhouri noted that he and his colleagues relied on items 121 and 130 of the NHANES Alcohol Use Questionnaire, which are self-reported by participants.

“Obviously, we’re not going to get honest answers all the time,” he said. “We’ve seen even in NASH [nonalcoholic steatohepatitis] clinical trials that when patients say they do not drink any alcohol, if you actually look for alcohol metabolites, up to 20% may have some evidence of alcohol consumption.

“I’m sure there’s a lot of overlap, but there’s no formal assessment,” he added.

Dr. Alkhouri noted that among the cohort with ALD, obesity and increased A1c were prevalent, “so it goes both ways. I think NAFLD can also contribute to progression of ALD, and that’s why we need to study another entity called ‘both alcoholic and nonalcoholic fatty liver disease.’”

Dr. Vos suggested that biomarkers may be useful for detecting alcohol use among patients with NAFLD and for further study of the progression of NAFLD to ALD.

No source of funding for the study has been disclosed. Dr. Alkhouri and Dr. Vos reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two-fifths of adolescents and young adults in the United States may have nonalcoholic fatty liver disease (NAFLD), many with significant or advanced fibrosis, results of a nationwide surveillance study suggest.

In addition, among those who drink alcohol in excess, slightly more than half may have alcohol-associated fatty liver disease (ALD) that may lead to moderate to severe fibrosis in a substantial proportion, said Naim Alkhouri, MD, from Arizona Liver Health, Peoria, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Efforts should focus on increasing awareness of the burden of ALD and NAFLD in this population and [mitigating] modifiable risk factors to prevent disease development and disease progression to potentially advanced fibrosis and cirrhosis,” he said.
 

Liver stiffness measured

Unlike previous studies that relied on liver enzyme levels or ultrasonography to estimate the prevalence of fatty liver disease among adolescents and young adults in the United States, Dr. Alkhouri and colleagues used valid liver ultrasonographic elastography (FibroScan) measurements, recorded during 2017-2018, from the National Health and Nutrition Examination Survey (NHANES) database.

The sample included participants aged 15 to 39 years. Those with viral hepatitis, alanine aminotransferase (ALT) levels greater than 500 U/L, or pregnancy were excluded.

The investigators divided the participants into those with excessive alcohol consumption, defined using the NHANES Alcohol Use Questionnaire as having more than two drinks per day for males or more than one drink per day for females, and those with no excessive alcohol consumption.

The authors used controlled attenuation parameters to identify participants with suspected ALD or NAFLD.

They then used liver stiffness measurement cutoffs of greater than or equal to 7.5 kPa to identify moderate fibrosis and greater than or equal to 9.5 kPa to identify severe fibrosis in those with evidence of ALD and cutoffs of greater than or equal to 6.1 kPa and greater than or equal to 7.1 kPa, respectively, in those with suspected NAFLD.

The cutoffs were chosen to maximize sensitivity, as determined from published literature, Dr. Alkhouri said.
 

Uncovering a high prevalence of ALD and NAFLD

The final sample comprised 1,319 participants, including 100 with excessive alcohol use and 1,219 without.

The heavy drinkers were significantly more likely to be older, male, White, current smokers, have lower platelet counts, higher aspartate aminotransferase (AST) and ALT levels, and higher mean corpuscular volumes.

Among the excessive drinkers, 52% had ALD. Of this group, 87.7% had either no or mild fibrosis, and 12.3% had moderate to severe fibrosis.

Among patients with excessive alcohol consumption, significant predictors of ALD included male sex, higher body mass index, ALT greater than the upper limit of normal, and higher A1c percentage.

Among those who were moderate drinkers or abstemious, 40% had NAFLD. Of this subgroup, 68.9% had no or mild fibrosis, and 31.1% had moderate to severe fibrosis.

Predictors of NAFLD in this group included older age, male sex, higher body mass index, and elevated ALT, AST, albumin, platelet counts, and A1c.
 

Is drinking underreported?

In a question-and-answer session following the presentation, co-moderator Miriam B. Vos, MD, a pediatric hepatologist at Children’s Healthcare of Atlanta, asked Dr. Alkhouri about his confidence in the accuracy of the measurements of alcohol consumption and whether there could be significant overlap between the ALD and NAFLD populations.

Dr. Alkhouri noted that he and his colleagues relied on items 121 and 130 of the NHANES Alcohol Use Questionnaire, which are self-reported by participants.

“Obviously, we’re not going to get honest answers all the time,” he said. “We’ve seen even in NASH [nonalcoholic steatohepatitis] clinical trials that when patients say they do not drink any alcohol, if you actually look for alcohol metabolites, up to 20% may have some evidence of alcohol consumption.

“I’m sure there’s a lot of overlap, but there’s no formal assessment,” he added.

Dr. Alkhouri noted that among the cohort with ALD, obesity and increased A1c were prevalent, “so it goes both ways. I think NAFLD can also contribute to progression of ALD, and that’s why we need to study another entity called ‘both alcoholic and nonalcoholic fatty liver disease.’”

Dr. Vos suggested that biomarkers may be useful for detecting alcohol use among patients with NAFLD and for further study of the progression of NAFLD to ALD.

No source of funding for the study has been disclosed. Dr. Alkhouri and Dr. Vos reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The decision to initiate biologics early in the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) should be based on complication risk, not on the assumption that earlier treatment produces better results, new research suggests.

Results of a meta-analysis of randomized controlled trials show that “the proportional biologic/placebo treatment effect on remission and response to biologics was not influenced by disease duration in UC or CD patients,” the investigators note.

“Patients with Crohn’s disease treated with biologics early on show over 40% remission rate, compared [with] around 30% for those with disease of 20 years or more,” study investigator Shomron Ben-Horin, MD, Sheba Medical Center, Tel Aviv University, Israel, told this news organization.

The rates of remission with both biologics and placebo were higher for patients with short-duration CD compared with patients with disease of longer duration. However, for patients with UC, the remission rates with both biologics and placebo were similar regardless of disease duration.

“Our findings support the use of biologics in patients with Crohn’s disease early after diagnosis, if they are at high risk of disease progression and complications, but not just to achieve better efficacy,” Dr. Ben-Horin said.

The meta-analysis was published online in Gastroenterology.
 

Getting the timing right

Dr. Ben-Horin led the research with an international group of investigators who assessed individual data from 6,168 patients with CD and 3,227 patients with UC. The patients were participants in 25 placebo-controlled trials.

For patients with CD, the odds ratio of achieving remission with biologics in comparison with placebo was 1.47 (95% confidence interval, 1.01-2.15) for short-duration disease (≤18 months), which was not so different from the odds ratio for longer-duration disease (>18 months) (OR, 1.43; 95% CI, 1.19-1.72).

“These results remained similar when tested for other disease duration cutoffs or when accounting for individual patients’ characteristics, such as whether patients were previously exposed to biologics or not,” said Dr. Ben-Horin.

For patients with UC, the OR for remission with biologics in comparison with placebo was 1.82 (95% CI, 1.12-2.97) for those with short-duration disease and 2.21 (95% CI, 1.79-2.72) for those with long-duration disease.

What the optimal timing is for using biologics for patients with inflammatory bowel disease (IBD), which includes both CD and UC, and whether all patients with these conditions need them are very pertinent questions, said Dr. Ben-Horin.

About a decade ago, the treatment of IBD changed. At that time, patients were initially treated with immunomodulators or steroids; biologics were used only if those treatments failed. More recently, a top-down approach has been followed, in which biologics are brought in at the beginning of the treatment protocol, said Dr. Ben-Horin.

This top-down approach has been widely adopted to prevent complications, such as intestinal strictures, bowel obstruction, or fistulas, which can increase the odds that patients with CD will require surgery, he added.

Although treatment with biologics was more effective when initiated earlier than later, data to support this were limited, prompting the investigators to conduct the current review.

“A substantial fraction of patients with Crohn’s disease may be better off with biologics first if they are at a high risk of complications: for example, smokers, patients with extensive disease, or those with perianal fistula. But this may not be necessarily true for those with a low risk of complications,” said Dr. Ben-Horin.

For patients with UC, “the lack of better efficacy with biologics in short-duration disease forces us to rethink our protocols of an early start of biologics,” he added.
 

Possible reasons for the early response

The reasons for the higher response to both placebo and biologics for patients with early CD are unknown.

“It may be that there is plasticity in Crohn’s disease early in the course of disease, where the tissue is more amenable to return to normal whether the patient is on placebo or treatment,” said Dr. Ben-Horin.

He suspects that the more likely explanation is that the placebo response is higher in patients with CD of short duration.

“When we looked at levels of C-reactive protein, this was reduced by biologics at similar magnitude in early- and late-disease patients,” Dr. Ben-Horin said. He noted that more studies are needed to better understand disease dynamics with these conditions.

Commenting on the findings, Stephen B. Hanauer, MD, from Northwestern University Feinberg School of Medicine, Chicago, noted that they “absolutely support earlier intervention for moderate-severe Crohn’s disease from diagnosis, rather than waiting for transmural progression that will make disease more refractory to any mechanism of action.”

“Unfortunately, the average duration of disease in biologic trials is often close to 10 years, which implies a more refractory population,” Dr. Hanauer said.

“Furthermore, in the United States, clinicians and patients are hampered by inability to gain third-party authorization for biologics or advanced oral agents, such as JAK inhibitors or S1P modulators, until failure of so-called conventional agents despite labeling indication for moderate-severe disease,” he added.

Dr. Ben-Horin has received consultancy and/or advisory board fees from AbbVie, Novartis, Schering-Plough, Janssen, Celltrion, GSK, Pfizer, Galmed, and Takeda and research support from AbbVie, Janssen, Celltrion, Galmed, and Takeda. Dr. Hanauer is a consultant and speaker for AbbVie, Janssen, and Takeda.

A version of this article first appeared on Medscape.com.

The decision to initiate biologics early in the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) should be based on complication risk, not on the assumption that earlier treatment produces better results, new research suggests.

Results of a meta-analysis of randomized controlled trials show that “the proportional biologic/placebo treatment effect on remission and response to biologics was not influenced by disease duration in UC or CD patients,” the investigators note.

“Patients with Crohn’s disease treated with biologics early on show over 40% remission rate, compared [with] around 30% for those with disease of 20 years or more,” study investigator Shomron Ben-Horin, MD, Sheba Medical Center, Tel Aviv University, Israel, told this news organization.

The rates of remission with both biologics and placebo were higher for patients with short-duration CD compared with patients with disease of longer duration. However, for patients with UC, the remission rates with both biologics and placebo were similar regardless of disease duration.

“Our findings support the use of biologics in patients with Crohn’s disease early after diagnosis, if they are at high risk of disease progression and complications, but not just to achieve better efficacy,” Dr. Ben-Horin said.

The meta-analysis was published online in Gastroenterology.
 

Getting the timing right

Dr. Ben-Horin led the research with an international group of investigators who assessed individual data from 6,168 patients with CD and 3,227 patients with UC. The patients were participants in 25 placebo-controlled trials.

For patients with CD, the odds ratio of achieving remission with biologics in comparison with placebo was 1.47 (95% confidence interval, 1.01-2.15) for short-duration disease (≤18 months), which was not so different from the odds ratio for longer-duration disease (>18 months) (OR, 1.43; 95% CI, 1.19-1.72).

“These results remained similar when tested for other disease duration cutoffs or when accounting for individual patients’ characteristics, such as whether patients were previously exposed to biologics or not,” said Dr. Ben-Horin.

For patients with UC, the OR for remission with biologics in comparison with placebo was 1.82 (95% CI, 1.12-2.97) for those with short-duration disease and 2.21 (95% CI, 1.79-2.72) for those with long-duration disease.

What the optimal timing is for using biologics for patients with inflammatory bowel disease (IBD), which includes both CD and UC, and whether all patients with these conditions need them are very pertinent questions, said Dr. Ben-Horin.

About a decade ago, the treatment of IBD changed. At that time, patients were initially treated with immunomodulators or steroids; biologics were used only if those treatments failed. More recently, a top-down approach has been followed, in which biologics are brought in at the beginning of the treatment protocol, said Dr. Ben-Horin.

This top-down approach has been widely adopted to prevent complications, such as intestinal strictures, bowel obstruction, or fistulas, which can increase the odds that patients with CD will require surgery, he added.

Although treatment with biologics was more effective when initiated earlier than later, data to support this were limited, prompting the investigators to conduct the current review.

“A substantial fraction of patients with Crohn’s disease may be better off with biologics first if they are at a high risk of complications: for example, smokers, patients with extensive disease, or those with perianal fistula. But this may not be necessarily true for those with a low risk of complications,” said Dr. Ben-Horin.

For patients with UC, “the lack of better efficacy with biologics in short-duration disease forces us to rethink our protocols of an early start of biologics,” he added.
 

Possible reasons for the early response

The reasons for the higher response to both placebo and biologics for patients with early CD are unknown.

“It may be that there is plasticity in Crohn’s disease early in the course of disease, where the tissue is more amenable to return to normal whether the patient is on placebo or treatment,” said Dr. Ben-Horin.

He suspects that the more likely explanation is that the placebo response is higher in patients with CD of short duration.

“When we looked at levels of C-reactive protein, this was reduced by biologics at similar magnitude in early- and late-disease patients,” Dr. Ben-Horin said. He noted that more studies are needed to better understand disease dynamics with these conditions.

Commenting on the findings, Stephen B. Hanauer, MD, from Northwestern University Feinberg School of Medicine, Chicago, noted that they “absolutely support earlier intervention for moderate-severe Crohn’s disease from diagnosis, rather than waiting for transmural progression that will make disease more refractory to any mechanism of action.”

“Unfortunately, the average duration of disease in biologic trials is often close to 10 years, which implies a more refractory population,” Dr. Hanauer said.

“Furthermore, in the United States, clinicians and patients are hampered by inability to gain third-party authorization for biologics or advanced oral agents, such as JAK inhibitors or S1P modulators, until failure of so-called conventional agents despite labeling indication for moderate-severe disease,” he added.

Dr. Ben-Horin has received consultancy and/or advisory board fees from AbbVie, Novartis, Schering-Plough, Janssen, Celltrion, GSK, Pfizer, Galmed, and Takeda and research support from AbbVie, Janssen, Celltrion, Galmed, and Takeda. Dr. Hanauer is a consultant and speaker for AbbVie, Janssen, and Takeda.

A version of this article first appeared on Medscape.com.

The decision to initiate biologics early in the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) should be based on complication risk, not on the assumption that earlier treatment produces better results, new research suggests.

Results of a meta-analysis of randomized controlled trials show that “the proportional biologic/placebo treatment effect on remission and response to biologics was not influenced by disease duration in UC or CD patients,” the investigators note.

“Patients with Crohn’s disease treated with biologics early on show over 40% remission rate, compared [with] around 30% for those with disease of 20 years or more,” study investigator Shomron Ben-Horin, MD, Sheba Medical Center, Tel Aviv University, Israel, told this news organization.

The rates of remission with both biologics and placebo were higher for patients with short-duration CD compared with patients with disease of longer duration. However, for patients with UC, the remission rates with both biologics and placebo were similar regardless of disease duration.

“Our findings support the use of biologics in patients with Crohn’s disease early after diagnosis, if they are at high risk of disease progression and complications, but not just to achieve better efficacy,” Dr. Ben-Horin said.

The meta-analysis was published online in Gastroenterology.
 

Getting the timing right

Dr. Ben-Horin led the research with an international group of investigators who assessed individual data from 6,168 patients with CD and 3,227 patients with UC. The patients were participants in 25 placebo-controlled trials.

For patients with CD, the odds ratio of achieving remission with biologics in comparison with placebo was 1.47 (95% confidence interval, 1.01-2.15) for short-duration disease (≤18 months), which was not so different from the odds ratio for longer-duration disease (>18 months) (OR, 1.43; 95% CI, 1.19-1.72).

“These results remained similar when tested for other disease duration cutoffs or when accounting for individual patients’ characteristics, such as whether patients were previously exposed to biologics or not,” said Dr. Ben-Horin.

For patients with UC, the OR for remission with biologics in comparison with placebo was 1.82 (95% CI, 1.12-2.97) for those with short-duration disease and 2.21 (95% CI, 1.79-2.72) for those with long-duration disease.

What the optimal timing is for using biologics for patients with inflammatory bowel disease (IBD), which includes both CD and UC, and whether all patients with these conditions need them are very pertinent questions, said Dr. Ben-Horin.

About a decade ago, the treatment of IBD changed. At that time, patients were initially treated with immunomodulators or steroids; biologics were used only if those treatments failed. More recently, a top-down approach has been followed, in which biologics are brought in at the beginning of the treatment protocol, said Dr. Ben-Horin.

This top-down approach has been widely adopted to prevent complications, such as intestinal strictures, bowel obstruction, or fistulas, which can increase the odds that patients with CD will require surgery, he added.

Although treatment with biologics was more effective when initiated earlier than later, data to support this were limited, prompting the investigators to conduct the current review.

“A substantial fraction of patients with Crohn’s disease may be better off with biologics first if they are at a high risk of complications: for example, smokers, patients with extensive disease, or those with perianal fistula. But this may not be necessarily true for those with a low risk of complications,” said Dr. Ben-Horin.

For patients with UC, “the lack of better efficacy with biologics in short-duration disease forces us to rethink our protocols of an early start of biologics,” he added.
 

Possible reasons for the early response

The reasons for the higher response to both placebo and biologics for patients with early CD are unknown.

“It may be that there is plasticity in Crohn’s disease early in the course of disease, where the tissue is more amenable to return to normal whether the patient is on placebo or treatment,” said Dr. Ben-Horin.

He suspects that the more likely explanation is that the placebo response is higher in patients with CD of short duration.

“When we looked at levels of C-reactive protein, this was reduced by biologics at similar magnitude in early- and late-disease patients,” Dr. Ben-Horin said. He noted that more studies are needed to better understand disease dynamics with these conditions.

Commenting on the findings, Stephen B. Hanauer, MD, from Northwestern University Feinberg School of Medicine, Chicago, noted that they “absolutely support earlier intervention for moderate-severe Crohn’s disease from diagnosis, rather than waiting for transmural progression that will make disease more refractory to any mechanism of action.”

“Unfortunately, the average duration of disease in biologic trials is often close to 10 years, which implies a more refractory population,” Dr. Hanauer said.

“Furthermore, in the United States, clinicians and patients are hampered by inability to gain third-party authorization for biologics or advanced oral agents, such as JAK inhibitors or S1P modulators, until failure of so-called conventional agents despite labeling indication for moderate-severe disease,” he added.

Dr. Ben-Horin has received consultancy and/or advisory board fees from AbbVie, Novartis, Schering-Plough, Janssen, Celltrion, GSK, Pfizer, Galmed, and Takeda and research support from AbbVie, Janssen, Celltrion, Galmed, and Takeda. Dr. Hanauer is a consultant and speaker for AbbVie, Janssen, and Takeda.

A version of this article first appeared on Medscape.com.

More than half of chronic hepatitis B e antigen–negative patients who withdraw from nucleoside or nucleotide analogue therapy experienced relapse within 4 years, according to a new study that looked at patients from 11 centers in Europe, North America, and Asia.

“We wanted to see if the patients stabilize after that year. Are they just having relapses within the first year, and then they’re inactive carriers? Especially patients who don’t achieve [hepatitis B surface antigen; HBsAg] loss. Is that mildly active disease? Would they have been better off being retreated, or are they better off [staying off] therapy? It is important to look at what happens among these patients who stop and if there is a way to tell which way they’re going to go,” said Grishma Hirode, who is a PhD candidate at the University of Toronto. Ms. Hirode presented the multinational study at the annual meeting of the American Association for the Study of Liver Diseases.

The study provided a clear picture: “They do not stabilize after 1 year. They have relapses, and these relapses aren’t mild fluctuations,” said Ms. Hirode. Another study, which was presented during the same session and investigated a national cohort in Taiwan, also found a high rate of flareups and retreatment out to 4 years.

The RETRACT-B study presented by Ms. Hirode collected data on 945 patients from 11 centers in North America, Europe, and Asia. Overall, 66% had at least one relapse within 1 year of drug withdrawal. At 2 years, 40% had a sustained remission without HBsAg loss, as had 20% at 4 years; 44% had sustained remission or HBsAg loss at 2 years, as did 30% at 4 years.

Subgroup analyses found differences between some populations: 48% of Whites and 28% of Asians had sustained remission or HBsAg loss, and 30% of Whites and 20% of Asians had sustained remission without HBsAg loss. Patients who were HBsAg positive at start of therapy were more likely to have a sustained remission or HBsAg loss (36% vs. 28%; P < .05) and to have a sustained remission without HBsAg loss (31% vs. 19%; P < .05). HBsAg levels below 100 IU/mL at cessation was also associated with a greater chance of sustained remission or HBsAg loss (58% vs. 24%; P < .05) and sustained remission without HBsAg loss (24% vs. 20%; P < .05). Not having a relapse within the first year after cessation was also associated with greater chance of sustained remission or HBsAg loss (50% versus 19%; P < .05) and sustained remission without HBsAg loss (37% vs. 13%; P < .05).

sarathsasidharan/Thinkstock

The Taiwan cohort study examined the repercussions of a government policy that limited reimbursement of nucleotide/nucleoside analogues to a fixed duration of time. Among 10,192 eligible patients, researchers at I-SHOU University found a 6.58% 4-year cumulative incidence of severe flare-ups after discontinuation (95% confidence interval, 5.91%-7.30%), defined as serum ALT levels higher than five times the upper limit of normal plus serum bilirubin levels above 2 mg/dL.

The overall incidence of flare-ups was 30.66% over 4 years (95% CI, 29.37%-31.96%). Higher risk of flareup was associated with older age (hazard ratio for each 10 years, 1.19; P<.0001), male sex (HR, 1.76; P < .0001), a diagnosis of cirrhosis (HR, 1.84; P < .0001), and a history of hepatic decompensation (HR, 1.45; P = .044).

The 4-year incidence of retreatment was 48.74% (95% CI, 46.55-50.90%)

The mortality rate was 0.63% at 4 years after a flareup (95% CI, 0.44-0.87%), and the combined rate of mortality or liver transplant was 0.79% (95% CI, 0.58-1.05%). Risk factors for higher mortality included older age (per 10 years; HR, 1.70; P < .0001), a diagnosis of cirrhosis (HR, 6.12; P < .0001), and hypertension (HR, 2.29; P = .029).
 

Selecting patients safely?

The results of both studies suggest that withdrawal from medication should be done cautiously, and patients monitored for relapse and retreatment, according to Anna Lok, MD, who was asked for comment. Dr. Lok is a professor of internal medicine, director of clinical hematology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

Between the two studies, “the message is that this approach can benefit some patients, but if the goal of treatment withdrawal is to increase the rate of hepatitis B surface antigen loss, only a small percentage of patients would benefit. Contrary to studies in Europe, the rates of HBsAg loss in studies with predominantly Asian patients are much lower,” said Dr. Lok.

The new studies provide guidance as for which patients might safely stop treatment; specifically, she suggested, young White patients who have a low HBsAg level when treatment is stopped. “But you probably shouldn’t be trying it in older Asian patients who still have high HBsAg titer, because the chance of them relapsing is very high and the chance of benefit is very low,” she said.

“One has to be very careful in selecting which patients you’re going to try this on. And if you do want to try, you’ve got to make sure that you monitor patients very carefully so treatment can be promptly resumed if necessary because some of the patients can have a severe flare and they can even develop liver failure, and this should never be tried in patients with cirrhosis” said Dr. Lok.

Ms. Hirode and Dr. Lok have no relevant financial disclosures.

More than half of chronic hepatitis B e antigen–negative patients who withdraw from nucleoside or nucleotide analogue therapy experienced relapse within 4 years, according to a new study that looked at patients from 11 centers in Europe, North America, and Asia.

“We wanted to see if the patients stabilize after that year. Are they just having relapses within the first year, and then they’re inactive carriers? Especially patients who don’t achieve [hepatitis B surface antigen; HBsAg] loss. Is that mildly active disease? Would they have been better off being retreated, or are they better off [staying off] therapy? It is important to look at what happens among these patients who stop and if there is a way to tell which way they’re going to go,” said Grishma Hirode, who is a PhD candidate at the University of Toronto. Ms. Hirode presented the multinational study at the annual meeting of the American Association for the Study of Liver Diseases.

The study provided a clear picture: “They do not stabilize after 1 year. They have relapses, and these relapses aren’t mild fluctuations,” said Ms. Hirode. Another study, which was presented during the same session and investigated a national cohort in Taiwan, also found a high rate of flareups and retreatment out to 4 years.

The RETRACT-B study presented by Ms. Hirode collected data on 945 patients from 11 centers in North America, Europe, and Asia. Overall, 66% had at least one relapse within 1 year of drug withdrawal. At 2 years, 40% had a sustained remission without HBsAg loss, as had 20% at 4 years; 44% had sustained remission or HBsAg loss at 2 years, as did 30% at 4 years.

Subgroup analyses found differences between some populations: 48% of Whites and 28% of Asians had sustained remission or HBsAg loss, and 30% of Whites and 20% of Asians had sustained remission without HBsAg loss. Patients who were HBsAg positive at start of therapy were more likely to have a sustained remission or HBsAg loss (36% vs. 28%; P < .05) and to have a sustained remission without HBsAg loss (31% vs. 19%; P < .05). HBsAg levels below 100 IU/mL at cessation was also associated with a greater chance of sustained remission or HBsAg loss (58% vs. 24%; P < .05) and sustained remission without HBsAg loss (24% vs. 20%; P < .05). Not having a relapse within the first year after cessation was also associated with greater chance of sustained remission or HBsAg loss (50% versus 19%; P < .05) and sustained remission without HBsAg loss (37% vs. 13%; P < .05).

sarathsasidharan/Thinkstock

The Taiwan cohort study examined the repercussions of a government policy that limited reimbursement of nucleotide/nucleoside analogues to a fixed duration of time. Among 10,192 eligible patients, researchers at I-SHOU University found a 6.58% 4-year cumulative incidence of severe flare-ups after discontinuation (95% confidence interval, 5.91%-7.30%), defined as serum ALT levels higher than five times the upper limit of normal plus serum bilirubin levels above 2 mg/dL.

The overall incidence of flare-ups was 30.66% over 4 years (95% CI, 29.37%-31.96%). Higher risk of flareup was associated with older age (hazard ratio for each 10 years, 1.19; P<.0001), male sex (HR, 1.76; P < .0001), a diagnosis of cirrhosis (HR, 1.84; P < .0001), and a history of hepatic decompensation (HR, 1.45; P = .044).

The 4-year incidence of retreatment was 48.74% (95% CI, 46.55-50.90%)

The mortality rate was 0.63% at 4 years after a flareup (95% CI, 0.44-0.87%), and the combined rate of mortality or liver transplant was 0.79% (95% CI, 0.58-1.05%). Risk factors for higher mortality included older age (per 10 years; HR, 1.70; P < .0001), a diagnosis of cirrhosis (HR, 6.12; P < .0001), and hypertension (HR, 2.29; P = .029).
 

Selecting patients safely?

The results of both studies suggest that withdrawal from medication should be done cautiously, and patients monitored for relapse and retreatment, according to Anna Lok, MD, who was asked for comment. Dr. Lok is a professor of internal medicine, director of clinical hematology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

Between the two studies, “the message is that this approach can benefit some patients, but if the goal of treatment withdrawal is to increase the rate of hepatitis B surface antigen loss, only a small percentage of patients would benefit. Contrary to studies in Europe, the rates of HBsAg loss in studies with predominantly Asian patients are much lower,” said Dr. Lok.

The new studies provide guidance as for which patients might safely stop treatment; specifically, she suggested, young White patients who have a low HBsAg level when treatment is stopped. “But you probably shouldn’t be trying it in older Asian patients who still have high HBsAg titer, because the chance of them relapsing is very high and the chance of benefit is very low,” she said.

“One has to be very careful in selecting which patients you’re going to try this on. And if you do want to try, you’ve got to make sure that you monitor patients very carefully so treatment can be promptly resumed if necessary because some of the patients can have a severe flare and they can even develop liver failure, and this should never be tried in patients with cirrhosis” said Dr. Lok.

Ms. Hirode and Dr. Lok have no relevant financial disclosures.

More than half of chronic hepatitis B e antigen–negative patients who withdraw from nucleoside or nucleotide analogue therapy experienced relapse within 4 years, according to a new study that looked at patients from 11 centers in Europe, North America, and Asia.

“We wanted to see if the patients stabilize after that year. Are they just having relapses within the first year, and then they’re inactive carriers? Especially patients who don’t achieve [hepatitis B surface antigen; HBsAg] loss. Is that mildly active disease? Would they have been better off being retreated, or are they better off [staying off] therapy? It is important to look at what happens among these patients who stop and if there is a way to tell which way they’re going to go,” said Grishma Hirode, who is a PhD candidate at the University of Toronto. Ms. Hirode presented the multinational study at the annual meeting of the American Association for the Study of Liver Diseases.

The study provided a clear picture: “They do not stabilize after 1 year. They have relapses, and these relapses aren’t mild fluctuations,” said Ms. Hirode. Another study, which was presented during the same session and investigated a national cohort in Taiwan, also found a high rate of flareups and retreatment out to 4 years.

The RETRACT-B study presented by Ms. Hirode collected data on 945 patients from 11 centers in North America, Europe, and Asia. Overall, 66% had at least one relapse within 1 year of drug withdrawal. At 2 years, 40% had a sustained remission without HBsAg loss, as had 20% at 4 years; 44% had sustained remission or HBsAg loss at 2 years, as did 30% at 4 years.

Subgroup analyses found differences between some populations: 48% of Whites and 28% of Asians had sustained remission or HBsAg loss, and 30% of Whites and 20% of Asians had sustained remission without HBsAg loss. Patients who were HBsAg positive at start of therapy were more likely to have a sustained remission or HBsAg loss (36% vs. 28%; P < .05) and to have a sustained remission without HBsAg loss (31% vs. 19%; P < .05). HBsAg levels below 100 IU/mL at cessation was also associated with a greater chance of sustained remission or HBsAg loss (58% vs. 24%; P < .05) and sustained remission without HBsAg loss (24% vs. 20%; P < .05). Not having a relapse within the first year after cessation was also associated with greater chance of sustained remission or HBsAg loss (50% versus 19%; P < .05) and sustained remission without HBsAg loss (37% vs. 13%; P < .05).

sarathsasidharan/Thinkstock

The Taiwan cohort study examined the repercussions of a government policy that limited reimbursement of nucleotide/nucleoside analogues to a fixed duration of time. Among 10,192 eligible patients, researchers at I-SHOU University found a 6.58% 4-year cumulative incidence of severe flare-ups after discontinuation (95% confidence interval, 5.91%-7.30%), defined as serum ALT levels higher than five times the upper limit of normal plus serum bilirubin levels above 2 mg/dL.

The overall incidence of flare-ups was 30.66% over 4 years (95% CI, 29.37%-31.96%). Higher risk of flareup was associated with older age (hazard ratio for each 10 years, 1.19; P<.0001), male sex (HR, 1.76; P < .0001), a diagnosis of cirrhosis (HR, 1.84; P < .0001), and a history of hepatic decompensation (HR, 1.45; P = .044).

The 4-year incidence of retreatment was 48.74% (95% CI, 46.55-50.90%)

The mortality rate was 0.63% at 4 years after a flareup (95% CI, 0.44-0.87%), and the combined rate of mortality or liver transplant was 0.79% (95% CI, 0.58-1.05%). Risk factors for higher mortality included older age (per 10 years; HR, 1.70; P < .0001), a diagnosis of cirrhosis (HR, 6.12; P < .0001), and hypertension (HR, 2.29; P = .029).
 

Selecting patients safely?

The results of both studies suggest that withdrawal from medication should be done cautiously, and patients monitored for relapse and retreatment, according to Anna Lok, MD, who was asked for comment. Dr. Lok is a professor of internal medicine, director of clinical hematology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

Between the two studies, “the message is that this approach can benefit some patients, but if the goal of treatment withdrawal is to increase the rate of hepatitis B surface antigen loss, only a small percentage of patients would benefit. Contrary to studies in Europe, the rates of HBsAg loss in studies with predominantly Asian patients are much lower,” said Dr. Lok.

The new studies provide guidance as for which patients might safely stop treatment; specifically, she suggested, young White patients who have a low HBsAg level when treatment is stopped. “But you probably shouldn’t be trying it in older Asian patients who still have high HBsAg titer, because the chance of them relapsing is very high and the chance of benefit is very low,” she said.

“One has to be very careful in selecting which patients you’re going to try this on. And if you do want to try, you’ve got to make sure that you monitor patients very carefully so treatment can be promptly resumed if necessary because some of the patients can have a severe flare and they can even develop liver failure, and this should never be tried in patients with cirrhosis” said Dr. Lok.

Ms. Hirode and Dr. Lok have no relevant financial disclosures.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

• Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
• Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
• Be aware that intrahepatic is more common with HCV.
• Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

• Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
• Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
• Be aware that intrahepatic is more common with HCV.
• Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

• Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
• Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
• Be aware that intrahepatic is more common with HCV.
• Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

For patients with nonalcoholic fatty liver disease (NAFLD) who supplement their diets with polyunsaturated fatty acids (PUFA), liver and metabolic parameters improve, results of a systematic review and meta-analysis suggest.

Data from randomized clinical trials show that, for participants with NAFLD who used PUFA supplements with or without additional dietary interventions, hepatic steatosis and lobular inflammation decreased, and in one study, fibrosis decreased. There were also improvements in liver enzyme levels, said Saleh Alqahtani, MBChB, associate professor of medicine at Johns Hopkins University, Baltimore, during a presentation at the annual meeting of the American Association for the Study of Liver Diseases.

“Since there’s no effective medical therapy for NAFLD, weight loss through lifestyle modifications becomes the most important focused intervention for patients with NAFLD,” he said. “However, the majority of patients fail to achieve or to maintain weight loss for long-term therapy. Therefore, dietary intervention or supplementation might help reduce the prevalence of NAFLD and decrease the progression of nonalcoholic steatohepatitis [NASH] and liver cirrhosis.

“More clinical trials are warranted to determine the long-term efficacy of the Mediterranean diet and polyunsaturated fatty acid supplementation among adult patients with NAFLD,” he added.
 

RCTs and case-control studies

It’s well documented that consumption of PUFAs, found in fatty fish and in canola, grapeseed, corn, and soybean oils, as well as monounsaturated fatty acids, found in olive oil and peanut oil, can contribute to improvement of NALFD, Dr. Alqahtani said.

In contrast, foods high in saturated fatty acids, such as butter, as well as trans fats and cholesterol can contribute to NAFLD progression, he said.

In their studies of intrahepatic triglyceride content, Dr. Alqahtani and colleagues found that fatty acids in the liver come from three major sources: dietary fatty acids, which account for about 15% of liver fat, tissue lipolysis, and de novo hepatic lipogenesis.

Previous systematic reviews and meta-analyses of the relationship between diet and NAFLD have focused on marine-based (n-3) PUFAs, but “the data regarding the evidence of unsaturated fatty acids through supplements or monounsaturated fatty acids through dietary supplementation are lacking,” he said.

To summarize the effects of dietary or supplemental fatty acids on liver and metabolic parameters in adults with NAFLD, Dr. Alqahtani and colleagues conducted a systematic review and meta-analysis, concentrating on studies that included specifics about interventions and outcomes.

They identified a total of 18 randomized controlled trials and 4 case-control studies that met their criteria. The studies were published from 2008 to 2020.

Regarding the effects of interventions on the components of NASH, they found that, in 1 or more of 12 randomized trials of PUFA supplementation with or without dietary interventions, there were associations with decreased hepatic steatosis, lobular inflammation, and fibrosis and declines in ALT and AST levels.

In three trials of dietary-only interventions, there were decreases in hepatic steatosis and ALT and/or AST levels. In two studies of the effects of healthy cooking oils only, hepatic steatosis decreased, but there was no effect on ALT or AST levels.

All three interventions were associated with improvements in fasting glucose levels and insulin metabolism, as well as decreases in total cholesterol, triglycerides, and LDL cholesterol and increases in HDL cholesterol.
 

Better understanding of dietary composition

“We’ve known for a while that dietary composition may impact NAFLD and NASH,” said Manal F. Abdelmalek, MD, professor of medicine at Duke University, Durham, N.C., who commented on the study.

“What [Dr. Alqahtani and colleagues] have shown is that supplementation with healthy fatty acids improves fatty liver. This really does extend our knowledge of what we understand about dietary composition, particularly the recommendations that support higher fish consumption and a Mediterranean-style diet,” she said.

“It’s not just about the fat but the type of fat that’s consumed, and drilling down to the particulars of dietary composition beyond calories alone,” she added.

No source of funding for the study has been disclosed. Dr. Alqahtani and Dr. Abdelmalek have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For patients with nonalcoholic fatty liver disease (NAFLD) who supplement their diets with polyunsaturated fatty acids (PUFA), liver and metabolic parameters improve, results of a systematic review and meta-analysis suggest.

Data from randomized clinical trials show that, for participants with NAFLD who used PUFA supplements with or without additional dietary interventions, hepatic steatosis and lobular inflammation decreased, and in one study, fibrosis decreased. There were also improvements in liver enzyme levels, said Saleh Alqahtani, MBChB, associate professor of medicine at Johns Hopkins University, Baltimore, during a presentation at the annual meeting of the American Association for the Study of Liver Diseases.

“Since there’s no effective medical therapy for NAFLD, weight loss through lifestyle modifications becomes the most important focused intervention for patients with NAFLD,” he said. “However, the majority of patients fail to achieve or to maintain weight loss for long-term therapy. Therefore, dietary intervention or supplementation might help reduce the prevalence of NAFLD and decrease the progression of nonalcoholic steatohepatitis [NASH] and liver cirrhosis.

“More clinical trials are warranted to determine the long-term efficacy of the Mediterranean diet and polyunsaturated fatty acid supplementation among adult patients with NAFLD,” he added.
 

RCTs and case-control studies

It’s well documented that consumption of PUFAs, found in fatty fish and in canola, grapeseed, corn, and soybean oils, as well as monounsaturated fatty acids, found in olive oil and peanut oil, can contribute to improvement of NALFD, Dr. Alqahtani said.

In contrast, foods high in saturated fatty acids, such as butter, as well as trans fats and cholesterol can contribute to NAFLD progression, he said.

In their studies of intrahepatic triglyceride content, Dr. Alqahtani and colleagues found that fatty acids in the liver come from three major sources: dietary fatty acids, which account for about 15% of liver fat, tissue lipolysis, and de novo hepatic lipogenesis.

Previous systematic reviews and meta-analyses of the relationship between diet and NAFLD have focused on marine-based (n-3) PUFAs, but “the data regarding the evidence of unsaturated fatty acids through supplements or monounsaturated fatty acids through dietary supplementation are lacking,” he said.

To summarize the effects of dietary or supplemental fatty acids on liver and metabolic parameters in adults with NAFLD, Dr. Alqahtani and colleagues conducted a systematic review and meta-analysis, concentrating on studies that included specifics about interventions and outcomes.

They identified a total of 18 randomized controlled trials and 4 case-control studies that met their criteria. The studies were published from 2008 to 2020.

Regarding the effects of interventions on the components of NASH, they found that, in 1 or more of 12 randomized trials of PUFA supplementation with or without dietary interventions, there were associations with decreased hepatic steatosis, lobular inflammation, and fibrosis and declines in ALT and AST levels.

In three trials of dietary-only interventions, there were decreases in hepatic steatosis and ALT and/or AST levels. In two studies of the effects of healthy cooking oils only, hepatic steatosis decreased, but there was no effect on ALT or AST levels.

All three interventions were associated with improvements in fasting glucose levels and insulin metabolism, as well as decreases in total cholesterol, triglycerides, and LDL cholesterol and increases in HDL cholesterol.
 

Better understanding of dietary composition

“We’ve known for a while that dietary composition may impact NAFLD and NASH,” said Manal F. Abdelmalek, MD, professor of medicine at Duke University, Durham, N.C., who commented on the study.

“What [Dr. Alqahtani and colleagues] have shown is that supplementation with healthy fatty acids improves fatty liver. This really does extend our knowledge of what we understand about dietary composition, particularly the recommendations that support higher fish consumption and a Mediterranean-style diet,” she said.

“It’s not just about the fat but the type of fat that’s consumed, and drilling down to the particulars of dietary composition beyond calories alone,” she added.

No source of funding for the study has been disclosed. Dr. Alqahtani and Dr. Abdelmalek have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For patients with nonalcoholic fatty liver disease (NAFLD) who supplement their diets with polyunsaturated fatty acids (PUFA), liver and metabolic parameters improve, results of a systematic review and meta-analysis suggest.

Data from randomized clinical trials show that, for participants with NAFLD who used PUFA supplements with or without additional dietary interventions, hepatic steatosis and lobular inflammation decreased, and in one study, fibrosis decreased. There were also improvements in liver enzyme levels, said Saleh Alqahtani, MBChB, associate professor of medicine at Johns Hopkins University, Baltimore, during a presentation at the annual meeting of the American Association for the Study of Liver Diseases.

“Since there’s no effective medical therapy for NAFLD, weight loss through lifestyle modifications becomes the most important focused intervention for patients with NAFLD,” he said. “However, the majority of patients fail to achieve or to maintain weight loss for long-term therapy. Therefore, dietary intervention or supplementation might help reduce the prevalence of NAFLD and decrease the progression of nonalcoholic steatohepatitis [NASH] and liver cirrhosis.

“More clinical trials are warranted to determine the long-term efficacy of the Mediterranean diet and polyunsaturated fatty acid supplementation among adult patients with NAFLD,” he added.
 

RCTs and case-control studies

It’s well documented that consumption of PUFAs, found in fatty fish and in canola, grapeseed, corn, and soybean oils, as well as monounsaturated fatty acids, found in olive oil and peanut oil, can contribute to improvement of NALFD, Dr. Alqahtani said.

In contrast, foods high in saturated fatty acids, such as butter, as well as trans fats and cholesterol can contribute to NAFLD progression, he said.

In their studies of intrahepatic triglyceride content, Dr. Alqahtani and colleagues found that fatty acids in the liver come from three major sources: dietary fatty acids, which account for about 15% of liver fat, tissue lipolysis, and de novo hepatic lipogenesis.

Previous systematic reviews and meta-analyses of the relationship between diet and NAFLD have focused on marine-based (n-3) PUFAs, but “the data regarding the evidence of unsaturated fatty acids through supplements or monounsaturated fatty acids through dietary supplementation are lacking,” he said.

To summarize the effects of dietary or supplemental fatty acids on liver and metabolic parameters in adults with NAFLD, Dr. Alqahtani and colleagues conducted a systematic review and meta-analysis, concentrating on studies that included specifics about interventions and outcomes.

They identified a total of 18 randomized controlled trials and 4 case-control studies that met their criteria. The studies were published from 2008 to 2020.

Regarding the effects of interventions on the components of NASH, they found that, in 1 or more of 12 randomized trials of PUFA supplementation with or without dietary interventions, there were associations with decreased hepatic steatosis, lobular inflammation, and fibrosis and declines in ALT and AST levels.

In three trials of dietary-only interventions, there were decreases in hepatic steatosis and ALT and/or AST levels. In two studies of the effects of healthy cooking oils only, hepatic steatosis decreased, but there was no effect on ALT or AST levels.

All three interventions were associated with improvements in fasting glucose levels and insulin metabolism, as well as decreases in total cholesterol, triglycerides, and LDL cholesterol and increases in HDL cholesterol.
 

Better understanding of dietary composition

“We’ve known for a while that dietary composition may impact NAFLD and NASH,” said Manal F. Abdelmalek, MD, professor of medicine at Duke University, Durham, N.C., who commented on the study.

“What [Dr. Alqahtani and colleagues] have shown is that supplementation with healthy fatty acids improves fatty liver. This really does extend our knowledge of what we understand about dietary composition, particularly the recommendations that support higher fish consumption and a Mediterranean-style diet,” she said.

“It’s not just about the fat but the type of fat that’s consumed, and drilling down to the particulars of dietary composition beyond calories alone,” she added.

No source of funding for the study has been disclosed. Dr. Alqahtani and Dr. Abdelmalek have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Multiple comorbidities appear to worsen mortality outcomes in patients with cirrhosis: Those with compensated cirrhosis and three comorbid conditions have a mortality rate similar to patients with decompensated cirrhosis, according to a new analysis of a population-based cohort in the Dallas-Fort Worth metroplex.

“I think it’s a pretty strong message that just the presence of these chronic diseases has such a strong effect in the long run. They at least contribute to mortality to some extent. It’s really important to focus on these chronic diseases as targets early during the care that we provide to these to cirrhotic patients to make sure that we control them so that, in the long run, we can decrease the premature death and mortality in these patients,” said Mohammad Amin Fallahzadeh, MD, MPH, who presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

The study included 35,361 patients with cirrhosis. The mean age of participants was 59.5 years, 41.8% were female, 29.7% were non-White, and 17.5% were Hispanic. Comorbidities were common, occurring in about 25% of patients. Forty-five percent of comorbidities were cardiovascular diseases (CVD); 28.9% of subjects had one comorbidity, 17.5% had two comorbidities, and 12.6% had three comorbidities.

A Kaplan-Meier curve showed that patients with compensated cirrhosis and no comorbidities had the highest survival over time, while decompensated patients with comorbidities had the lowest survival (P = .01). The curve showed similar survival between patients with compensated cirrhosis and three comorbidities and decompensated patients with no comorbidities.

The risk of death increased with one comorbidity (hazard ratio, 2.5; 95% confidence interval, 2.23-2.8), two comorbidities (HR, 3.27; 95% CI, 2.9-3.69), and three comorbidities (HR, 4.52; 95% CI, 3.99-5.12).

Mortality increased with the number of comorbidities in both compensated and decompensated patients; patients with hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease; by race (White, Black, and other); and in different age groups. A stronger effect of comorbidities was seen in compensated patients (HR, 6.4 vs. 4.1), female patients (HR, 5.2 vs. 4.1), and in patients older than age 65 years (HR, 7.2 vs. 3.7 in those aged 45-64 years and 5.0 in those younger than age 45 years).

The researchers also found an apparent synergistic effect of chronic kidney disease (CKD) and CVD. Both conditions were associated with increased risk on their own, but when a patient had both CVD and CKD, mortality was higher than just the added risk of the two conditions.

The findings confirm that patients with cirrhosis and comorbidities seem to have worse quality of life and higher mortality. “I didn’t expect that it would have such a major effect, to make a compensated patient as if they are decompensated, but we definitely see that in our daily practice,” said Dr. Fallahzadeh, who is a 2nd-year internal medicine resident at Baylor University Medical Center, Dallas.

“When a hepatologist or an internist has a visit with a patient who is diagnosed with cirrhosis, they need to screen them for the other chronic diseases like diabetes, CKD, and cardiovascular disease to make sure that if they have any of these conditions, they’ll be under control, or if they need any referral for better management. For example, if they need a nephrology referral, it [should] be done as early as possible so that we can minimize the burden of these diseases in the long run for these patients. And we need to educate the patients as well about controlling these chronic problems,” said Dr. Fallahzadeh.

The findings might make researchers reconsider how to classify compensated and decompensated cirrhosis. “When we talk about decompensated liver disease, we’re talking about variceal hemorrhage, ascites, and encephalopathy. In this case, they’re saying that if you’re compensated and you [have] three of these associated medical conditions, that you could be worse off than decompensated cirrhosis. It’s really challenging the status quo and how we think about these two disease entities. They’re thought of a lot differently in terms of the mortality. That needs to be further elucidated,” said Mayur Brahmania, MD, assistant professor of medicine at Western University, London, Ont., who moderated the session.

A key limitation to the study was that the researchers did not have access to data about medication use, so it could not be determined if comorbidities were being controlled. Body mass index and most lifestyle factors were also uncontrolled.

Dr. Fallahzadeh and Dr. Brahmania have no relevant financial disclosures.

Multiple comorbidities appear to worsen mortality outcomes in patients with cirrhosis: Those with compensated cirrhosis and three comorbid conditions have a mortality rate similar to patients with decompensated cirrhosis, according to a new analysis of a population-based cohort in the Dallas-Fort Worth metroplex.

“I think it’s a pretty strong message that just the presence of these chronic diseases has such a strong effect in the long run. They at least contribute to mortality to some extent. It’s really important to focus on these chronic diseases as targets early during the care that we provide to these to cirrhotic patients to make sure that we control them so that, in the long run, we can decrease the premature death and mortality in these patients,” said Mohammad Amin Fallahzadeh, MD, MPH, who presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

The study included 35,361 patients with cirrhosis. The mean age of participants was 59.5 years, 41.8% were female, 29.7% were non-White, and 17.5% were Hispanic. Comorbidities were common, occurring in about 25% of patients. Forty-five percent of comorbidities were cardiovascular diseases (CVD); 28.9% of subjects had one comorbidity, 17.5% had two comorbidities, and 12.6% had three comorbidities.

A Kaplan-Meier curve showed that patients with compensated cirrhosis and no comorbidities had the highest survival over time, while decompensated patients with comorbidities had the lowest survival (P = .01). The curve showed similar survival between patients with compensated cirrhosis and three comorbidities and decompensated patients with no comorbidities.

The risk of death increased with one comorbidity (hazard ratio, 2.5; 95% confidence interval, 2.23-2.8), two comorbidities (HR, 3.27; 95% CI, 2.9-3.69), and three comorbidities (HR, 4.52; 95% CI, 3.99-5.12).

Mortality increased with the number of comorbidities in both compensated and decompensated patients; patients with hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease; by race (White, Black, and other); and in different age groups. A stronger effect of comorbidities was seen in compensated patients (HR, 6.4 vs. 4.1), female patients (HR, 5.2 vs. 4.1), and in patients older than age 65 years (HR, 7.2 vs. 3.7 in those aged 45-64 years and 5.0 in those younger than age 45 years).

The researchers also found an apparent synergistic effect of chronic kidney disease (CKD) and CVD. Both conditions were associated with increased risk on their own, but when a patient had both CVD and CKD, mortality was higher than just the added risk of the two conditions.

The findings confirm that patients with cirrhosis and comorbidities seem to have worse quality of life and higher mortality. “I didn’t expect that it would have such a major effect, to make a compensated patient as if they are decompensated, but we definitely see that in our daily practice,” said Dr. Fallahzadeh, who is a 2nd-year internal medicine resident at Baylor University Medical Center, Dallas.

“When a hepatologist or an internist has a visit with a patient who is diagnosed with cirrhosis, they need to screen them for the other chronic diseases like diabetes, CKD, and cardiovascular disease to make sure that if they have any of these conditions, they’ll be under control, or if they need any referral for better management. For example, if they need a nephrology referral, it [should] be done as early as possible so that we can minimize the burden of these diseases in the long run for these patients. And we need to educate the patients as well about controlling these chronic problems,” said Dr. Fallahzadeh.

The findings might make researchers reconsider how to classify compensated and decompensated cirrhosis. “When we talk about decompensated liver disease, we’re talking about variceal hemorrhage, ascites, and encephalopathy. In this case, they’re saying that if you’re compensated and you [have] three of these associated medical conditions, that you could be worse off than decompensated cirrhosis. It’s really challenging the status quo and how we think about these two disease entities. They’re thought of a lot differently in terms of the mortality. That needs to be further elucidated,” said Mayur Brahmania, MD, assistant professor of medicine at Western University, London, Ont., who moderated the session.

A key limitation to the study was that the researchers did not have access to data about medication use, so it could not be determined if comorbidities were being controlled. Body mass index and most lifestyle factors were also uncontrolled.

Dr. Fallahzadeh and Dr. Brahmania have no relevant financial disclosures.

Multiple comorbidities appear to worsen mortality outcomes in patients with cirrhosis: Those with compensated cirrhosis and three comorbid conditions have a mortality rate similar to patients with decompensated cirrhosis, according to a new analysis of a population-based cohort in the Dallas-Fort Worth metroplex.

“I think it’s a pretty strong message that just the presence of these chronic diseases has such a strong effect in the long run. They at least contribute to mortality to some extent. It’s really important to focus on these chronic diseases as targets early during the care that we provide to these to cirrhotic patients to make sure that we control them so that, in the long run, we can decrease the premature death and mortality in these patients,” said Mohammad Amin Fallahzadeh, MD, MPH, who presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

The study included 35,361 patients with cirrhosis. The mean age of participants was 59.5 years, 41.8% were female, 29.7% were non-White, and 17.5% were Hispanic. Comorbidities were common, occurring in about 25% of patients. Forty-five percent of comorbidities were cardiovascular diseases (CVD); 28.9% of subjects had one comorbidity, 17.5% had two comorbidities, and 12.6% had three comorbidities.

A Kaplan-Meier curve showed that patients with compensated cirrhosis and no comorbidities had the highest survival over time, while decompensated patients with comorbidities had the lowest survival (P = .01). The curve showed similar survival between patients with compensated cirrhosis and three comorbidities and decompensated patients with no comorbidities.

The risk of death increased with one comorbidity (hazard ratio, 2.5; 95% confidence interval, 2.23-2.8), two comorbidities (HR, 3.27; 95% CI, 2.9-3.69), and three comorbidities (HR, 4.52; 95% CI, 3.99-5.12).

Mortality increased with the number of comorbidities in both compensated and decompensated patients; patients with hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease; by race (White, Black, and other); and in different age groups. A stronger effect of comorbidities was seen in compensated patients (HR, 6.4 vs. 4.1), female patients (HR, 5.2 vs. 4.1), and in patients older than age 65 years (HR, 7.2 vs. 3.7 in those aged 45-64 years and 5.0 in those younger than age 45 years).

The researchers also found an apparent synergistic effect of chronic kidney disease (CKD) and CVD. Both conditions were associated with increased risk on their own, but when a patient had both CVD and CKD, mortality was higher than just the added risk of the two conditions.

The findings confirm that patients with cirrhosis and comorbidities seem to have worse quality of life and higher mortality. “I didn’t expect that it would have such a major effect, to make a compensated patient as if they are decompensated, but we definitely see that in our daily practice,” said Dr. Fallahzadeh, who is a 2nd-year internal medicine resident at Baylor University Medical Center, Dallas.

“When a hepatologist or an internist has a visit with a patient who is diagnosed with cirrhosis, they need to screen them for the other chronic diseases like diabetes, CKD, and cardiovascular disease to make sure that if they have any of these conditions, they’ll be under control, or if they need any referral for better management. For example, if they need a nephrology referral, it [should] be done as early as possible so that we can minimize the burden of these diseases in the long run for these patients. And we need to educate the patients as well about controlling these chronic problems,” said Dr. Fallahzadeh.

The findings might make researchers reconsider how to classify compensated and decompensated cirrhosis. “When we talk about decompensated liver disease, we’re talking about variceal hemorrhage, ascites, and encephalopathy. In this case, they’re saying that if you’re compensated and you [have] three of these associated medical conditions, that you could be worse off than decompensated cirrhosis. It’s really challenging the status quo and how we think about these two disease entities. They’re thought of a lot differently in terms of the mortality. That needs to be further elucidated,” said Mayur Brahmania, MD, assistant professor of medicine at Western University, London, Ont., who moderated the session.

A key limitation to the study was that the researchers did not have access to data about medication use, so it could not be determined if comorbidities were being controlled. Body mass index and most lifestyle factors were also uncontrolled.

Dr. Fallahzadeh and Dr. Brahmania have no relevant financial disclosures.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase (ALT) and aspartate transaminase (AST) as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase (ALT) and aspartate transaminase (AST) as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase (ALT) and aspartate transaminase (AST) as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

LAS VEGAS – Over the course of the COVID-19 pandemic, alcohol-related liver disease has increased in severity, a finding that is likely related to higher consumption of alcohol and reduced care. The difference was notable in higher Model for End-Stage Liver Disease–sodium (MELD-Na) scores, more signs of hepatic decompensation, and higher mortality rates.

“Alcohol consumption during the COVID-19 pandemic led to increased morbidity and mortality, specifically in patients that already had underlying liver disease. The importance of alcohol cessation, counseling, and close physician monitoring is emphasized, given continued or relapsed alcohol consumption can significantly affect quality of life, life expectancy, and liver transplantation candidacy,” research team member Lindsay A. Sobotka, DO, said in an interview. Dr. Sobotka is an assistant professor of gastroenterology, hepatology, and nutrition at the Ohio State University Wexner Medical Center, Columbus.

The research was presented by Ayushi Jain, MD, at the annual meeting of the American College of Gastroenterology. Dr. Jain is a resident at the Ohio State University Wexner Medical Center.

Dr. Jain noted that alcohol sales have gone up during the pandemic, with monthly sales up 14%-44% between February and September 2020, compared with the same months in previous years.
 

Decompensation rates rose

The researchers analyzed data from patients with alcoholic cirrhosis or alcoholic hepatitis who were seen at the Ohio State University Medical Center between March and August 2019, and between March and August 2020.

alenkadr/Thinkstock

During the pandemic, the number of hospital admissions nearly doubled among alcoholic hepatitis patients (86 to 162), but declined slightly among patients with alcoholic cirrhosis (613 to 528), possibly because of efforts to manage decompensation and avoid hospitalizations during the pandemic, according to Dr. Jain. In total, 4 of 162 patients with alcoholic hepatitis and 14 of 528 patients with alcoholic cirrhosis had COVID-19 at the time of admission.

Higher mortality rates were seen during the pandemic, although this was only significant for alcoholic cirrhosis: 14.8% versus 7% for alcoholic hepatitis (P = .06) and 13.5% versus 7.4% for alcoholic cirrhosis (P = .001).

Among those with alcoholic hepatitis, there was no significant change in median Maddrey’s Discriminant Function during the pandemic (P = .51), but the researchers noted a significant decrease in steroid use, from 27 patients to 23 (P = .001). “This may be due to a statistically significant increase in GI bleeds and renal dysfunction that we noted during the pandemic,” said Dr. Jain.

Hepatic decompensation and critical care needs increased among patients admitted with alcoholic hepatitis, including hepatic encephalopathy (P = .037), gastrointestinal bleeding (P = .01), a need for increased oxygen (P = .024), vasopressor support (P = .005), and initiation of hemodialysis (P = .007). The median highest MELD-Na score during admission was also higher during the pandemic (24 vs. 23, P = .04).

Patients with alcoholic cirrhosis had greater decompensation as measured by ascites (P = .01), therapeutic paracentesis (P = .04), titration of diuretics (P = .005), acute kidney injury (P = .005), hepatorenal syndrome (P = .002), and spontaneous bacterial peritonitis (P = .04). They also had greater need for vasopressor support (9% to 14%; P = .006), were more likely to initiate hemodialysis (7% to 11%; P = .015), and had greater mortality (7% to 14%; P = .001).

In all, 212 patients reported increased alcohol intake, 161 reported little change over the past year, and 253 said they were abstinent. MELD-Na scores were highest in the increased group (27), compared with the unchanged group (24) and abstinent group (23) (P = .001).
 

More robust support needed

“This highlights that the increase in alcohol use seems to be associated with higher rates of more severe alcoholic hepatitis, and we are going to need to all be aware of and intervene in these individuals, and try to not only make health care more accessible, but help those with alcohol use disorder to reengage in some support systems [and] harm-reduction measures, to try to reduce the number of these episodes of admissions with severe alcoholic hepatitis,” said Paul Kwo, MD, who comoderated the session. Dr. Kwo is a professor of medicine at Stanford (Calif.) University.

Dr. Kwo suggested that the pandemic has presented dual challenges to patients with alcohol-related liver disease. One is that hospitals have filled up because of an influx of COVID-19 cases, which makes it hard for them to compete for limited resources. The other is that lockdowns and social interruptions may have interfered with the support systems that normally help them to keep sober and maintain health care. “The pandemic really disrupted everybody’s ecosystem substantially, and some of these individuals, as their ecosystems crumble, they don’t have other resources to engage in care, and then they present with far more advanced comorbidities than we might have seen prior to the pandemic,” said Dr. Kwo.

The findings underscore at least one lesson that can be drawn from the pandemic. “We now know that we have to develop more robust systems to provide support for all of these individuals,” said Dr. Kwo.

Comoderator Patricia D. Jones, MD, agreed, and expressed optimism. “We were forced develop more remote or virtual networks, so I think there are a lot of people that are taking advantage maybe of virtual [Alcoholics Anonymous], and that wasn’t something that they necessarily did [before the pandemic]. And so at least we’ve developed some parallel systems that hopefully people will benefit from,” said Dr. Jones, who is an assistant professor of medicine at the University of Miami.

She suggested that physicians should make inquiries about patients with alcohol-related liver disease and their social situations, and might consider trying to connect them to a social worker if called for. “I think that really speaking to the person about where they are would be beneficial,” said Dr. Jones.

Dr. Sobotka, Dr. Jain, Dr. Kwo, and Dr. Jones have no relevant financial disclosures.

LAS VEGAS – Over the course of the COVID-19 pandemic, alcohol-related liver disease has increased in severity, a finding that is likely related to higher consumption of alcohol and reduced care. The difference was notable in higher Model for End-Stage Liver Disease–sodium (MELD-Na) scores, more signs of hepatic decompensation, and higher mortality rates.

“Alcohol consumption during the COVID-19 pandemic led to increased morbidity and mortality, specifically in patients that already had underlying liver disease. The importance of alcohol cessation, counseling, and close physician monitoring is emphasized, given continued or relapsed alcohol consumption can significantly affect quality of life, life expectancy, and liver transplantation candidacy,” research team member Lindsay A. Sobotka, DO, said in an interview. Dr. Sobotka is an assistant professor of gastroenterology, hepatology, and nutrition at the Ohio State University Wexner Medical Center, Columbus.

The research was presented by Ayushi Jain, MD, at the annual meeting of the American College of Gastroenterology. Dr. Jain is a resident at the Ohio State University Wexner Medical Center.

Dr. Jain noted that alcohol sales have gone up during the pandemic, with monthly sales up 14%-44% between February and September 2020, compared with the same months in previous years.
 

Decompensation rates rose

The researchers analyzed data from patients with alcoholic cirrhosis or alcoholic hepatitis who were seen at the Ohio State University Medical Center between March and August 2019, and between March and August 2020.

alenkadr/Thinkstock

During the pandemic, the number of hospital admissions nearly doubled among alcoholic hepatitis patients (86 to 162), but declined slightly among patients with alcoholic cirrhosis (613 to 528), possibly because of efforts to manage decompensation and avoid hospitalizations during the pandemic, according to Dr. Jain. In total, 4 of 162 patients with alcoholic hepatitis and 14 of 528 patients with alcoholic cirrhosis had COVID-19 at the time of admission.

Higher mortality rates were seen during the pandemic, although this was only significant for alcoholic cirrhosis: 14.8% versus 7% for alcoholic hepatitis (P = .06) and 13.5% versus 7.4% for alcoholic cirrhosis (P = .001).

Among those with alcoholic hepatitis, there was no significant change in median Maddrey’s Discriminant Function during the pandemic (P = .51), but the researchers noted a significant decrease in steroid use, from 27 patients to 23 (P = .001). “This may be due to a statistically significant increase in GI bleeds and renal dysfunction that we noted during the pandemic,” said Dr. Jain.

Hepatic decompensation and critical care needs increased among patients admitted with alcoholic hepatitis, including hepatic encephalopathy (P = .037), gastrointestinal bleeding (P = .01), a need for increased oxygen (P = .024), vasopressor support (P = .005), and initiation of hemodialysis (P = .007). The median highest MELD-Na score during admission was also higher during the pandemic (24 vs. 23, P = .04).

Patients with alcoholic cirrhosis had greater decompensation as measured by ascites (P = .01), therapeutic paracentesis (P = .04), titration of diuretics (P = .005), acute kidney injury (P = .005), hepatorenal syndrome (P = .002), and spontaneous bacterial peritonitis (P = .04). They also had greater need for vasopressor support (9% to 14%; P = .006), were more likely to initiate hemodialysis (7% to 11%; P = .015), and had greater mortality (7% to 14%; P = .001).

In all, 212 patients reported increased alcohol intake, 161 reported little change over the past year, and 253 said they were abstinent. MELD-Na scores were highest in the increased group (27), compared with the unchanged group (24) and abstinent group (23) (P = .001).
 

More robust support needed

“This highlights that the increase in alcohol use seems to be associated with higher rates of more severe alcoholic hepatitis, and we are going to need to all be aware of and intervene in these individuals, and try to not only make health care more accessible, but help those with alcohol use disorder to reengage in some support systems [and] harm-reduction measures, to try to reduce the number of these episodes of admissions with severe alcoholic hepatitis,” said Paul Kwo, MD, who comoderated the session. Dr. Kwo is a professor of medicine at Stanford (Calif.) University.

Dr. Kwo suggested that the pandemic has presented dual challenges to patients with alcohol-related liver disease. One is that hospitals have filled up because of an influx of COVID-19 cases, which makes it hard for them to compete for limited resources. The other is that lockdowns and social interruptions may have interfered with the support systems that normally help them to keep sober and maintain health care. “The pandemic really disrupted everybody’s ecosystem substantially, and some of these individuals, as their ecosystems crumble, they don’t have other resources to engage in care, and then they present with far more advanced comorbidities than we might have seen prior to the pandemic,” said Dr. Kwo.

The findings underscore at least one lesson that can be drawn from the pandemic. “We now know that we have to develop more robust systems to provide support for all of these individuals,” said Dr. Kwo.

Comoderator Patricia D. Jones, MD, agreed, and expressed optimism. “We were forced develop more remote or virtual networks, so I think there are a lot of people that are taking advantage maybe of virtual [Alcoholics Anonymous], and that wasn’t something that they necessarily did [before the pandemic]. And so at least we’ve developed some parallel systems that hopefully people will benefit from,” said Dr. Jones, who is an assistant professor of medicine at the University of Miami.

She suggested that physicians should make inquiries about patients with alcohol-related liver disease and their social situations, and might consider trying to connect them to a social worker if called for. “I think that really speaking to the person about where they are would be beneficial,” said Dr. Jones.

Dr. Sobotka, Dr. Jain, Dr. Kwo, and Dr. Jones have no relevant financial disclosures.

LAS VEGAS – Over the course of the COVID-19 pandemic, alcohol-related liver disease has increased in severity, a finding that is likely related to higher consumption of alcohol and reduced care. The difference was notable in higher Model for End-Stage Liver Disease–sodium (MELD-Na) scores, more signs of hepatic decompensation, and higher mortality rates.

“Alcohol consumption during the COVID-19 pandemic led to increased morbidity and mortality, specifically in patients that already had underlying liver disease. The importance of alcohol cessation, counseling, and close physician monitoring is emphasized, given continued or relapsed alcohol consumption can significantly affect quality of life, life expectancy, and liver transplantation candidacy,” research team member Lindsay A. Sobotka, DO, said in an interview. Dr. Sobotka is an assistant professor of gastroenterology, hepatology, and nutrition at the Ohio State University Wexner Medical Center, Columbus.

The research was presented by Ayushi Jain, MD, at the annual meeting of the American College of Gastroenterology. Dr. Jain is a resident at the Ohio State University Wexner Medical Center.

Dr. Jain noted that alcohol sales have gone up during the pandemic, with monthly sales up 14%-44% between February and September 2020, compared with the same months in previous years.
 

Decompensation rates rose

The researchers analyzed data from patients with alcoholic cirrhosis or alcoholic hepatitis who were seen at the Ohio State University Medical Center between March and August 2019, and between March and August 2020.

alenkadr/Thinkstock

During the pandemic, the number of hospital admissions nearly doubled among alcoholic hepatitis patients (86 to 162), but declined slightly among patients with alcoholic cirrhosis (613 to 528), possibly because of efforts to manage decompensation and avoid hospitalizations during the pandemic, according to Dr. Jain. In total, 4 of 162 patients with alcoholic hepatitis and 14 of 528 patients with alcoholic cirrhosis had COVID-19 at the time of admission.

Higher mortality rates were seen during the pandemic, although this was only significant for alcoholic cirrhosis: 14.8% versus 7% for alcoholic hepatitis (P = .06) and 13.5% versus 7.4% for alcoholic cirrhosis (P = .001).

Among those with alcoholic hepatitis, there was no significant change in median Maddrey’s Discriminant Function during the pandemic (P = .51), but the researchers noted a significant decrease in steroid use, from 27 patients to 23 (P = .001). “This may be due to a statistically significant increase in GI bleeds and renal dysfunction that we noted during the pandemic,” said Dr. Jain.

Hepatic decompensation and critical care needs increased among patients admitted with alcoholic hepatitis, including hepatic encephalopathy (P = .037), gastrointestinal bleeding (P = .01), a need for increased oxygen (P = .024), vasopressor support (P = .005), and initiation of hemodialysis (P = .007). The median highest MELD-Na score during admission was also higher during the pandemic (24 vs. 23, P = .04).

Patients with alcoholic cirrhosis had greater decompensation as measured by ascites (P = .01), therapeutic paracentesis (P = .04), titration of diuretics (P = .005), acute kidney injury (P = .005), hepatorenal syndrome (P = .002), and spontaneous bacterial peritonitis (P = .04). They also had greater need for vasopressor support (9% to 14%; P = .006), were more likely to initiate hemodialysis (7% to 11%; P = .015), and had greater mortality (7% to 14%; P = .001).

In all, 212 patients reported increased alcohol intake, 161 reported little change over the past year, and 253 said they were abstinent. MELD-Na scores were highest in the increased group (27), compared with the unchanged group (24) and abstinent group (23) (P = .001).
 

More robust support needed

“This highlights that the increase in alcohol use seems to be associated with higher rates of more severe alcoholic hepatitis, and we are going to need to all be aware of and intervene in these individuals, and try to not only make health care more accessible, but help those with alcohol use disorder to reengage in some support systems [and] harm-reduction measures, to try to reduce the number of these episodes of admissions with severe alcoholic hepatitis,” said Paul Kwo, MD, who comoderated the session. Dr. Kwo is a professor of medicine at Stanford (Calif.) University.

Dr. Kwo suggested that the pandemic has presented dual challenges to patients with alcohol-related liver disease. One is that hospitals have filled up because of an influx of COVID-19 cases, which makes it hard for them to compete for limited resources. The other is that lockdowns and social interruptions may have interfered with the support systems that normally help them to keep sober and maintain health care. “The pandemic really disrupted everybody’s ecosystem substantially, and some of these individuals, as their ecosystems crumble, they don’t have other resources to engage in care, and then they present with far more advanced comorbidities than we might have seen prior to the pandemic,” said Dr. Kwo.

The findings underscore at least one lesson that can be drawn from the pandemic. “We now know that we have to develop more robust systems to provide support for all of these individuals,” said Dr. Kwo.

Comoderator Patricia D. Jones, MD, agreed, and expressed optimism. “We were forced develop more remote or virtual networks, so I think there are a lot of people that are taking advantage maybe of virtual [Alcoholics Anonymous], and that wasn’t something that they necessarily did [before the pandemic]. And so at least we’ve developed some parallel systems that hopefully people will benefit from,” said Dr. Jones, who is an assistant professor of medicine at the University of Miami.

She suggested that physicians should make inquiries about patients with alcohol-related liver disease and their social situations, and might consider trying to connect them to a social worker if called for. “I think that really speaking to the person about where they are would be beneficial,” said Dr. Jones.

Dr. Sobotka, Dr. Jain, Dr. Kwo, and Dr. Jones have no relevant financial disclosures.