Liver Disease

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

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

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

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

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

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

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

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

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

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

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

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

Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.

Shidlovski/Getty Images

Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.

In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.

“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
 

Surprising findings

The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).

A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.

Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.

However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”

Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”

Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.

The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.

However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
 

Knowledge gaps and implications

The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”

Dr. Banini said that some of the findings were to be expected, while others were not.

“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.

“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.

“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.

“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”

“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”

He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”

The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.

Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.

Shidlovski/Getty Images

Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.

In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.

“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
 

Surprising findings

The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).

A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.

Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.

However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”

Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”

Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.

The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.

However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
 

Knowledge gaps and implications

The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”

Dr. Banini said that some of the findings were to be expected, while others were not.

“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.

“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.

“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.

“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”

“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”

He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”

The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.

Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.

Shidlovski/Getty Images

Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.

In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.

“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
 

Surprising findings

The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).

A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.

Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.

However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”

Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”

Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.

The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.

However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
 

Knowledge gaps and implications

The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”

Dr. Banini said that some of the findings were to be expected, while others were not.

“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.

“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.

“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.

“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”

“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”

He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”

The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.

In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.

Among almost 100,000 patients with severe obesity (body mass index >40 kg/m²) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.

Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.

It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.

“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”

Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.

Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.

Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
 

Rising rates of fatty liver disease, obesity

An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.

NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.

Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.

Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.

Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.

Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.

One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.

Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
 

Does bariatric surgery curb cancer risk in liver disease?

The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.

Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.

Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).

During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.

A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).

The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.

The authors disclosed no relevant financial relationships.

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

In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.

Among almost 100,000 patients with severe obesity (body mass index >40 kg/m²) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.

Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.

It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.

“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”

Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.

Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.

Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
 

Rising rates of fatty liver disease, obesity

An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.

NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.

Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.

Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.

Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.

Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.

One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.

Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
 

Does bariatric surgery curb cancer risk in liver disease?

The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.

Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.

Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).

During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.

A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).

The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.

The authors disclosed no relevant financial relationships.

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

In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.

Among almost 100,000 patients with severe obesity (body mass index >40 kg/m²) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.

Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.

It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.

“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”

Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.

Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.

Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
 

Rising rates of fatty liver disease, obesity

An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.

NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.

Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.

Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.

Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.

Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.

One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.

Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
 

Does bariatric surgery curb cancer risk in liver disease?

The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.

Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.

Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).

During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.

A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).

The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.

The authors disclosed no relevant financial relationships.

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

Nonalcoholic fatty liver disease (NAFLD) in children is almost always caused by excess body weight, not other etiologies, based on a retrospective analysis of 900 patients.

Just 2% of children with overweight or obesity and suspected NAFLD had other causes of liver disease, and none tested positive for autoimmune hepatitis (AIH), reported lead author Toshifumi Yodoshi, MD, PhD, of Cincinnati Children’s Hospital Medical Center, and colleagues.

“Currently, recommended testing of patients with suspected NAFLD includes ruling out the following conditions: AIH, Wilson disease, hemochromatosis, alpha-1 antitrypsin [A1AT] deficiency, viral hepatitis, celiac disease, and thyroid dysfunction,” the investigators wrote in Pediatrics.

Yet evidence supporting this particular battery of tests is scant; just one previous pediatric study has estimated the prevalence of other liver diseases among children with suspected NAFLD. The study showed that the second-most common etiology, after NAFLD, was AIH, at a rate of 4%.

But “the generalizability of these findings is uncertain,” noted Dr. Yodoshi and colleagues, as the study was conducted at one tertiary center in the western United States, among a population that was predominantly Hispanic.

This uncertainty spurred the present study, which was conducted at two pediatric centers: Cincinnati Children’s Hospital Medical Center (2009-2017) and Yale New Haven (Conn.) Children’s Hospital (2012-2017).

The final analysis involved 900 patients aged 18 years or younger with suspected NAFLD based on hepatic steatosis detected via imaging and/or elevated serum aminotransferases. Demographically, a slight majority of the patients were boys (63%), and approximately one-quarter (26%) were Hispanic. Median BMI z score was 2.45, with three out of four patients (76%) exhibiting severe obesity. Out of 900 patients, 358 (40%) underwent liver biopsy, among whom 46% had confirmed nonalcoholic steatohepatitis.

All patients underwent testing to exclude the aforementioned conditions using various diagnostics, revealing that just 2% of the population had etiologies other than NAFLD. Specifically, 11 children had thyroid dysfunction (1.2%), 3 had celiac disease (0.4%), 3 had A1AT deficiency (0.4%), 1 had hemophagocytic lymphohistiocytosis, and 1 had Hodgkin’s lymphoma. None of the children had Wilson disease, hepatitis B or C, or AIH.

Dr. Yodoshi and colleagues highlighted the latter finding, noting that 13% of the patients had autoantibodies for AIH, but “none met composite criteria.” This contrasts with the previous study from 2013, which found an AIH rate of 4%.

“Nonetheless,” the investigators went on, “NAFLD remains a diagnosis of exclusion, and key conditions that require specific treatments must be ruled out in the workup of patients with suspected NAFLD. In the future, the cost-effectiveness of this approach will need to be investigated.”

Interpreting the findings, Francis E. Rushton, MD, of Beaufort (S.C.) Memorial Hospital emphasized the implications for preventive and interventional health care.

“This study showing an absence of etiologies other than obesity in overweight children with NAFLD provides further impetus for pediatricians to work on both preventive and treatment regimens for weight issues,” Dr. Rushton said. “Linking community-based initiatives focused on adequate nutritional support with pediatric clinical support services is critical in solving issues related to overweight in children. Tracking BMI over time and developing healthy habit goals for patients are key parts of clinical interventions.” 

The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.

Nonalcoholic fatty liver disease (NAFLD) in children is almost always caused by excess body weight, not other etiologies, based on a retrospective analysis of 900 patients.

Just 2% of children with overweight or obesity and suspected NAFLD had other causes of liver disease, and none tested positive for autoimmune hepatitis (AIH), reported lead author Toshifumi Yodoshi, MD, PhD, of Cincinnati Children’s Hospital Medical Center, and colleagues.

“Currently, recommended testing of patients with suspected NAFLD includes ruling out the following conditions: AIH, Wilson disease, hemochromatosis, alpha-1 antitrypsin [A1AT] deficiency, viral hepatitis, celiac disease, and thyroid dysfunction,” the investigators wrote in Pediatrics.

Yet evidence supporting this particular battery of tests is scant; just one previous pediatric study has estimated the prevalence of other liver diseases among children with suspected NAFLD. The study showed that the second-most common etiology, after NAFLD, was AIH, at a rate of 4%.

But “the generalizability of these findings is uncertain,” noted Dr. Yodoshi and colleagues, as the study was conducted at one tertiary center in the western United States, among a population that was predominantly Hispanic.

This uncertainty spurred the present study, which was conducted at two pediatric centers: Cincinnati Children’s Hospital Medical Center (2009-2017) and Yale New Haven (Conn.) Children’s Hospital (2012-2017).

The final analysis involved 900 patients aged 18 years or younger with suspected NAFLD based on hepatic steatosis detected via imaging and/or elevated serum aminotransferases. Demographically, a slight majority of the patients were boys (63%), and approximately one-quarter (26%) were Hispanic. Median BMI z score was 2.45, with three out of four patients (76%) exhibiting severe obesity. Out of 900 patients, 358 (40%) underwent liver biopsy, among whom 46% had confirmed nonalcoholic steatohepatitis.

All patients underwent testing to exclude the aforementioned conditions using various diagnostics, revealing that just 2% of the population had etiologies other than NAFLD. Specifically, 11 children had thyroid dysfunction (1.2%), 3 had celiac disease (0.4%), 3 had A1AT deficiency (0.4%), 1 had hemophagocytic lymphohistiocytosis, and 1 had Hodgkin’s lymphoma. None of the children had Wilson disease, hepatitis B or C, or AIH.

Dr. Yodoshi and colleagues highlighted the latter finding, noting that 13% of the patients had autoantibodies for AIH, but “none met composite criteria.” This contrasts with the previous study from 2013, which found an AIH rate of 4%.

“Nonetheless,” the investigators went on, “NAFLD remains a diagnosis of exclusion, and key conditions that require specific treatments must be ruled out in the workup of patients with suspected NAFLD. In the future, the cost-effectiveness of this approach will need to be investigated.”

Interpreting the findings, Francis E. Rushton, MD, of Beaufort (S.C.) Memorial Hospital emphasized the implications for preventive and interventional health care.

“This study showing an absence of etiologies other than obesity in overweight children with NAFLD provides further impetus for pediatricians to work on both preventive and treatment regimens for weight issues,” Dr. Rushton said. “Linking community-based initiatives focused on adequate nutritional support with pediatric clinical support services is critical in solving issues related to overweight in children. Tracking BMI over time and developing healthy habit goals for patients are key parts of clinical interventions.” 

The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.

Nonalcoholic fatty liver disease (NAFLD) in children is almost always caused by excess body weight, not other etiologies, based on a retrospective analysis of 900 patients.

Just 2% of children with overweight or obesity and suspected NAFLD had other causes of liver disease, and none tested positive for autoimmune hepatitis (AIH), reported lead author Toshifumi Yodoshi, MD, PhD, of Cincinnati Children’s Hospital Medical Center, and colleagues.

“Currently, recommended testing of patients with suspected NAFLD includes ruling out the following conditions: AIH, Wilson disease, hemochromatosis, alpha-1 antitrypsin [A1AT] deficiency, viral hepatitis, celiac disease, and thyroid dysfunction,” the investigators wrote in Pediatrics.

Yet evidence supporting this particular battery of tests is scant; just one previous pediatric study has estimated the prevalence of other liver diseases among children with suspected NAFLD. The study showed that the second-most common etiology, after NAFLD, was AIH, at a rate of 4%.

But “the generalizability of these findings is uncertain,” noted Dr. Yodoshi and colleagues, as the study was conducted at one tertiary center in the western United States, among a population that was predominantly Hispanic.

This uncertainty spurred the present study, which was conducted at two pediatric centers: Cincinnati Children’s Hospital Medical Center (2009-2017) and Yale New Haven (Conn.) Children’s Hospital (2012-2017).

The final analysis involved 900 patients aged 18 years or younger with suspected NAFLD based on hepatic steatosis detected via imaging and/or elevated serum aminotransferases. Demographically, a slight majority of the patients were boys (63%), and approximately one-quarter (26%) were Hispanic. Median BMI z score was 2.45, with three out of four patients (76%) exhibiting severe obesity. Out of 900 patients, 358 (40%) underwent liver biopsy, among whom 46% had confirmed nonalcoholic steatohepatitis.

All patients underwent testing to exclude the aforementioned conditions using various diagnostics, revealing that just 2% of the population had etiologies other than NAFLD. Specifically, 11 children had thyroid dysfunction (1.2%), 3 had celiac disease (0.4%), 3 had A1AT deficiency (0.4%), 1 had hemophagocytic lymphohistiocytosis, and 1 had Hodgkin’s lymphoma. None of the children had Wilson disease, hepatitis B or C, or AIH.

Dr. Yodoshi and colleagues highlighted the latter finding, noting that 13% of the patients had autoantibodies for AIH, but “none met composite criteria.” This contrasts with the previous study from 2013, which found an AIH rate of 4%.

“Nonetheless,” the investigators went on, “NAFLD remains a diagnosis of exclusion, and key conditions that require specific treatments must be ruled out in the workup of patients with suspected NAFLD. In the future, the cost-effectiveness of this approach will need to be investigated.”

Interpreting the findings, Francis E. Rushton, MD, of Beaufort (S.C.) Memorial Hospital emphasized the implications for preventive and interventional health care.

“This study showing an absence of etiologies other than obesity in overweight children with NAFLD provides further impetus for pediatricians to work on both preventive and treatment regimens for weight issues,” Dr. Rushton said. “Linking community-based initiatives focused on adequate nutritional support with pediatric clinical support services is critical in solving issues related to overweight in children. Tracking BMI over time and developing healthy habit goals for patients are key parts of clinical interventions.” 

The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.

These days deciding when to stop targeted treatment for chronic hepatitis B is a bigger challenge than knowing when to start, Norah A. Terrault, MD, MPH, observed at the Gastroenterology Updates, IBD, Liver Disease Conference.

Tetra Images/Getty Images

That’s because the treatment paradigm is in flux. The strategy is shifting from achieving hepatitis B virus (HBV) DNA suppression through indefinite use of nucleoside analogues to striving for functional cure, which means eliminating hepatitis B surface antigen (HBsAg) and sustained inactive chronic hepatitis B off therapy. It’s a goal that recognizes that, while suppression is worthwhile because it reduces a patient’s risk of hepatocellular carcinoma, HBsAg clearance is better because it’s associated with an even lower risk of the malignancy, explained Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.

The current strategy in patients who are hepatitis B e antigen (HBeAg) positive at the outset is to treat with a nucleoside analogue until seroconversion, followed by a further year or more of consolidation therapy then treatment withdrawal. It’s a rational approach whose primary benefit is it allows identification of the roughly 50% of patients who can remain off treatment with inactive chronic hepatitis B. The other 50% – those who experience clinical relapse – will need retreatment.

Factors predictive of increased likelihood of a sustained off-treatment response include age younger than 40 years at the time of seroconversion, more than 1 year of consolidation therapy, and undetectable HBV DNA at cessation of treatment.

“In my own practice now, I actually extend the consolidation period for 2 years before I consider stopping, and I really favor doing a trial of stopping treatment in those who are younger,” Dr. Terrault said.

The biggest change in thinking involves the duration of therapy in patients who are HBeAg negative. The strategy has been to treat indefinitely unless there is a compelling reason to stop, such as toxicity, cost, or patient preference. However, it has now been demonstrated in at least nine published studies that withdrawal of therapy has a favorable immunologic effect in noncirrhotic patients with HBeAg-negative chronic hepatitis B who have been HBV DNA negative on nucleoside analogues for at least 3 years. This trial off therapy can bring major benefits because roughly 50% of patients will have sustained inactive chronic hepatitis B off-treatment and 20% of patients will become HbsAg negative with functional cure at 3-5 years of follow-up.

“This is what’s impressive: that 20% of patients have lost surface antigen, because if you continue HbeAg-negative patients on nucleoside analogue therapy, essentially none of them lose surface antigen. This is an impressive number, and you’re also able to identify about 50% of patients who didn’t need to be on treatment because they now have immune control and can remain inactive carriers off treatment,” the gastroenterologist commented.

Treatment withdrawal in HBeAg-negative patients usually is followed by disease flares 8-12 weeks later because of host immune clearance, and therein lies a problem.

“The challenge with the withdrawal strategy is these flares that appear to be necessary and important, can be good or bad, and we’re really not very good at predicting what the flare is going to look like and how severe it’s going to be,” according to Dr. Terrault, first author of the current American Association for the Study of Liver Diseases guidance on prevention, diagnosis, and treatment of chronic hepatitis B.

The good flares are accompanied by a reductions in HBV DNA and viral proteins, loss of HbsAg, and preserved liver function. The bad flares entail excessive host immune clearance leading to liver dysfunction or failure, with no reduction in viral proteins. The search is on for predictors of response to treatment withdrawal in HbeAg-negative patients. Potential differences in outcomes with the three available nucleoside analogues are being looked at, as are duration of viral suppression on treatment and differences in patient characteristics. A low quantitative HbsAg level at the time of drug withdrawal may also be important as a predictor of a higher likelihood of HBsAg loss over time off treatment.

“The studies that have been done are basically withdrawing everyone and then seeing what happens. I think we want to have a more refined approach,” she said.

This is an unfolding story. The encouraging news is that the drug development pipeline is rich with agents with a variety of mechanisms aimed at achieving HbsAg loss with finite therapy. Some of the studies are now in phase 2 and 3.

“We should be extremely excited,” Dr. Terrault said. “I think in the future we’re very likely to have curative therapies in a much greater proportion of our patients.”
 

When to start nucleoside analogues

Three antiviral oral nucleoside analogues are available as preferred therapies for chronic HBV: entecavir (Baraclude), tenofovir alafenamide (Vemlidy), and tenofovir disoproxil (Viread). All three provide high antiviral efficacy and low risk for resistance. The treatment goal is to prevent disease progression and HBV complications, including hepatocellular carcinoma, in individuals with active chronic hepatitis B.

The major liver disease medical societies differ only slightly on the criteria for starting treatment. Broadly, they recommend starting therapy in all patients with cirrhosis, as well as in patients without cirrhosis who have both a serum ALT level more than twice the upper limit of normal and elevated HBV DNA levels. The treatment threshold for HBV DNA levels is higher in patients who are HBeAg positive than it is for patients who are HBeAg negative; for example, the American Association for the Study of Liver Diseases recommends that an HbeAg-positive patient should have a HBV DNA titer greater than 20,000 IU/mL, which is a level 10 times higher than the group’s treatment threshold in HBeAg-negative patients. However, these thresholds are intended as guidance, not absolute rules, Dr. Terrault emphasized. Nearly 40% of patients don’t meet the dual ALT and HBV DNA thresholds, and serial monitoring of such patients for 6-12 months is recommended because they may be in transition.

The choice of nucleoside analogue is largely based on comorbidities. Any of the three preferred antivirals can be used when there are none. Tenofovir disoproxil is preferred in pregnancy because of its safety profile in that setting. In patients who are aged over 60 years or have bone disease or renal impairment, tenofovir alafenamide and entecavir are preferred. Entecavir should be avoided in favor of either form of tenofovir in patients who are HIV positive or have prior exposure to lamivudine.

Regarding treatment with these drugs, the recommendations target those whose liver disease is being driven by active HBV rather than fatty liver disease or some other cause. That’s the reason for the reserving treatment for patients with both high HBV DNA and high serum ALT.

“There’s definitely a camp that feels these are safe drugs, easy to use, and we should treat more people. I have to say I’m not hanging out in that camp. I still feel we should do targeted treatment, especially since there are many new drugs coming where we’re going to be able to offer cure to more people. So I feel like putting everybody on suppressive therapy isn’t the answer,” she said.

Dr. Terrault receives research grants from and/or serves as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

These days deciding when to stop targeted treatment for chronic hepatitis B is a bigger challenge than knowing when to start, Norah A. Terrault, MD, MPH, observed at the Gastroenterology Updates, IBD, Liver Disease Conference.

Tetra Images/Getty Images

That’s because the treatment paradigm is in flux. The strategy is shifting from achieving hepatitis B virus (HBV) DNA suppression through indefinite use of nucleoside analogues to striving for functional cure, which means eliminating hepatitis B surface antigen (HBsAg) and sustained inactive chronic hepatitis B off therapy. It’s a goal that recognizes that, while suppression is worthwhile because it reduces a patient’s risk of hepatocellular carcinoma, HBsAg clearance is better because it’s associated with an even lower risk of the malignancy, explained Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.

The current strategy in patients who are hepatitis B e antigen (HBeAg) positive at the outset is to treat with a nucleoside analogue until seroconversion, followed by a further year or more of consolidation therapy then treatment withdrawal. It’s a rational approach whose primary benefit is it allows identification of the roughly 50% of patients who can remain off treatment with inactive chronic hepatitis B. The other 50% – those who experience clinical relapse – will need retreatment.

Factors predictive of increased likelihood of a sustained off-treatment response include age younger than 40 years at the time of seroconversion, more than 1 year of consolidation therapy, and undetectable HBV DNA at cessation of treatment.

“In my own practice now, I actually extend the consolidation period for 2 years before I consider stopping, and I really favor doing a trial of stopping treatment in those who are younger,” Dr. Terrault said.

The biggest change in thinking involves the duration of therapy in patients who are HBeAg negative. The strategy has been to treat indefinitely unless there is a compelling reason to stop, such as toxicity, cost, or patient preference. However, it has now been demonstrated in at least nine published studies that withdrawal of therapy has a favorable immunologic effect in noncirrhotic patients with HBeAg-negative chronic hepatitis B who have been HBV DNA negative on nucleoside analogues for at least 3 years. This trial off therapy can bring major benefits because roughly 50% of patients will have sustained inactive chronic hepatitis B off-treatment and 20% of patients will become HbsAg negative with functional cure at 3-5 years of follow-up.

“This is what’s impressive: that 20% of patients have lost surface antigen, because if you continue HbeAg-negative patients on nucleoside analogue therapy, essentially none of them lose surface antigen. This is an impressive number, and you’re also able to identify about 50% of patients who didn’t need to be on treatment because they now have immune control and can remain inactive carriers off treatment,” the gastroenterologist commented.

Treatment withdrawal in HBeAg-negative patients usually is followed by disease flares 8-12 weeks later because of host immune clearance, and therein lies a problem.

“The challenge with the withdrawal strategy is these flares that appear to be necessary and important, can be good or bad, and we’re really not very good at predicting what the flare is going to look like and how severe it’s going to be,” according to Dr. Terrault, first author of the current American Association for the Study of Liver Diseases guidance on prevention, diagnosis, and treatment of chronic hepatitis B.

The good flares are accompanied by a reductions in HBV DNA and viral proteins, loss of HbsAg, and preserved liver function. The bad flares entail excessive host immune clearance leading to liver dysfunction or failure, with no reduction in viral proteins. The search is on for predictors of response to treatment withdrawal in HbeAg-negative patients. Potential differences in outcomes with the three available nucleoside analogues are being looked at, as are duration of viral suppression on treatment and differences in patient characteristics. A low quantitative HbsAg level at the time of drug withdrawal may also be important as a predictor of a higher likelihood of HBsAg loss over time off treatment.

“The studies that have been done are basically withdrawing everyone and then seeing what happens. I think we want to have a more refined approach,” she said.

This is an unfolding story. The encouraging news is that the drug development pipeline is rich with agents with a variety of mechanisms aimed at achieving HbsAg loss with finite therapy. Some of the studies are now in phase 2 and 3.

“We should be extremely excited,” Dr. Terrault said. “I think in the future we’re very likely to have curative therapies in a much greater proportion of our patients.”
 

When to start nucleoside analogues

Three antiviral oral nucleoside analogues are available as preferred therapies for chronic HBV: entecavir (Baraclude), tenofovir alafenamide (Vemlidy), and tenofovir disoproxil (Viread). All three provide high antiviral efficacy and low risk for resistance. The treatment goal is to prevent disease progression and HBV complications, including hepatocellular carcinoma, in individuals with active chronic hepatitis B.

The major liver disease medical societies differ only slightly on the criteria for starting treatment. Broadly, they recommend starting therapy in all patients with cirrhosis, as well as in patients without cirrhosis who have both a serum ALT level more than twice the upper limit of normal and elevated HBV DNA levels. The treatment threshold for HBV DNA levels is higher in patients who are HBeAg positive than it is for patients who are HBeAg negative; for example, the American Association for the Study of Liver Diseases recommends that an HbeAg-positive patient should have a HBV DNA titer greater than 20,000 IU/mL, which is a level 10 times higher than the group’s treatment threshold in HBeAg-negative patients. However, these thresholds are intended as guidance, not absolute rules, Dr. Terrault emphasized. Nearly 40% of patients don’t meet the dual ALT and HBV DNA thresholds, and serial monitoring of such patients for 6-12 months is recommended because they may be in transition.

The choice of nucleoside analogue is largely based on comorbidities. Any of the three preferred antivirals can be used when there are none. Tenofovir disoproxil is preferred in pregnancy because of its safety profile in that setting. In patients who are aged over 60 years or have bone disease or renal impairment, tenofovir alafenamide and entecavir are preferred. Entecavir should be avoided in favor of either form of tenofovir in patients who are HIV positive or have prior exposure to lamivudine.

Regarding treatment with these drugs, the recommendations target those whose liver disease is being driven by active HBV rather than fatty liver disease or some other cause. That’s the reason for the reserving treatment for patients with both high HBV DNA and high serum ALT.

“There’s definitely a camp that feels these are safe drugs, easy to use, and we should treat more people. I have to say I’m not hanging out in that camp. I still feel we should do targeted treatment, especially since there are many new drugs coming where we’re going to be able to offer cure to more people. So I feel like putting everybody on suppressive therapy isn’t the answer,” she said.

Dr. Terrault receives research grants from and/or serves as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

These days deciding when to stop targeted treatment for chronic hepatitis B is a bigger challenge than knowing when to start, Norah A. Terrault, MD, MPH, observed at the Gastroenterology Updates, IBD, Liver Disease Conference.

Tetra Images/Getty Images

That’s because the treatment paradigm is in flux. The strategy is shifting from achieving hepatitis B virus (HBV) DNA suppression through indefinite use of nucleoside analogues to striving for functional cure, which means eliminating hepatitis B surface antigen (HBsAg) and sustained inactive chronic hepatitis B off therapy. It’s a goal that recognizes that, while suppression is worthwhile because it reduces a patient’s risk of hepatocellular carcinoma, HBsAg clearance is better because it’s associated with an even lower risk of the malignancy, explained Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.

The current strategy in patients who are hepatitis B e antigen (HBeAg) positive at the outset is to treat with a nucleoside analogue until seroconversion, followed by a further year or more of consolidation therapy then treatment withdrawal. It’s a rational approach whose primary benefit is it allows identification of the roughly 50% of patients who can remain off treatment with inactive chronic hepatitis B. The other 50% – those who experience clinical relapse – will need retreatment.

Factors predictive of increased likelihood of a sustained off-treatment response include age younger than 40 years at the time of seroconversion, more than 1 year of consolidation therapy, and undetectable HBV DNA at cessation of treatment.

“In my own practice now, I actually extend the consolidation period for 2 years before I consider stopping, and I really favor doing a trial of stopping treatment in those who are younger,” Dr. Terrault said.

The biggest change in thinking involves the duration of therapy in patients who are HBeAg negative. The strategy has been to treat indefinitely unless there is a compelling reason to stop, such as toxicity, cost, or patient preference. However, it has now been demonstrated in at least nine published studies that withdrawal of therapy has a favorable immunologic effect in noncirrhotic patients with HBeAg-negative chronic hepatitis B who have been HBV DNA negative on nucleoside analogues for at least 3 years. This trial off therapy can bring major benefits because roughly 50% of patients will have sustained inactive chronic hepatitis B off-treatment and 20% of patients will become HbsAg negative with functional cure at 3-5 years of follow-up.

“This is what’s impressive: that 20% of patients have lost surface antigen, because if you continue HbeAg-negative patients on nucleoside analogue therapy, essentially none of them lose surface antigen. This is an impressive number, and you’re also able to identify about 50% of patients who didn’t need to be on treatment because they now have immune control and can remain inactive carriers off treatment,” the gastroenterologist commented.

Treatment withdrawal in HBeAg-negative patients usually is followed by disease flares 8-12 weeks later because of host immune clearance, and therein lies a problem.

“The challenge with the withdrawal strategy is these flares that appear to be necessary and important, can be good or bad, and we’re really not very good at predicting what the flare is going to look like and how severe it’s going to be,” according to Dr. Terrault, first author of the current American Association for the Study of Liver Diseases guidance on prevention, diagnosis, and treatment of chronic hepatitis B.

The good flares are accompanied by a reductions in HBV DNA and viral proteins, loss of HbsAg, and preserved liver function. The bad flares entail excessive host immune clearance leading to liver dysfunction or failure, with no reduction in viral proteins. The search is on for predictors of response to treatment withdrawal in HbeAg-negative patients. Potential differences in outcomes with the three available nucleoside analogues are being looked at, as are duration of viral suppression on treatment and differences in patient characteristics. A low quantitative HbsAg level at the time of drug withdrawal may also be important as a predictor of a higher likelihood of HBsAg loss over time off treatment.

“The studies that have been done are basically withdrawing everyone and then seeing what happens. I think we want to have a more refined approach,” she said.

This is an unfolding story. The encouraging news is that the drug development pipeline is rich with agents with a variety of mechanisms aimed at achieving HbsAg loss with finite therapy. Some of the studies are now in phase 2 and 3.

“We should be extremely excited,” Dr. Terrault said. “I think in the future we’re very likely to have curative therapies in a much greater proportion of our patients.”
 

When to start nucleoside analogues

Three antiviral oral nucleoside analogues are available as preferred therapies for chronic HBV: entecavir (Baraclude), tenofovir alafenamide (Vemlidy), and tenofovir disoproxil (Viread). All three provide high antiviral efficacy and low risk for resistance. The treatment goal is to prevent disease progression and HBV complications, including hepatocellular carcinoma, in individuals with active chronic hepatitis B.

The major liver disease medical societies differ only slightly on the criteria for starting treatment. Broadly, they recommend starting therapy in all patients with cirrhosis, as well as in patients without cirrhosis who have both a serum ALT level more than twice the upper limit of normal and elevated HBV DNA levels. The treatment threshold for HBV DNA levels is higher in patients who are HBeAg positive than it is for patients who are HBeAg negative; for example, the American Association for the Study of Liver Diseases recommends that an HbeAg-positive patient should have a HBV DNA titer greater than 20,000 IU/mL, which is a level 10 times higher than the group’s treatment threshold in HBeAg-negative patients. However, these thresholds are intended as guidance, not absolute rules, Dr. Terrault emphasized. Nearly 40% of patients don’t meet the dual ALT and HBV DNA thresholds, and serial monitoring of such patients for 6-12 months is recommended because they may be in transition.

The choice of nucleoside analogue is largely based on comorbidities. Any of the three preferred antivirals can be used when there are none. Tenofovir disoproxil is preferred in pregnancy because of its safety profile in that setting. In patients who are aged over 60 years or have bone disease or renal impairment, tenofovir alafenamide and entecavir are preferred. Entecavir should be avoided in favor of either form of tenofovir in patients who are HIV positive or have prior exposure to lamivudine.

Regarding treatment with these drugs, the recommendations target those whose liver disease is being driven by active HBV rather than fatty liver disease or some other cause. That’s the reason for the reserving treatment for patients with both high HBV DNA and high serum ALT.

“There’s definitely a camp that feels these are safe drugs, easy to use, and we should treat more people. I have to say I’m not hanging out in that camp. I still feel we should do targeted treatment, especially since there are many new drugs coming where we’re going to be able to offer cure to more people. So I feel like putting everybody on suppressive therapy isn’t the answer,” she said.

Dr. Terrault receives research grants from and/or serves as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.