Non-Heavy Alcohol Use Associated With Liver Fibrosis, NASH

Carolyn Crist

December 21, 2022

Non-heavy alcohol use — fewer than 14 drinks per week for women and fewer than 21 drinks per week for men — is associated with liver fibrosis and nonalcoholic steatohepatitis (NASH), according to a new report.

An analysis of current drinkers in the Framingham Heart Study found that a higher number of drinks per week and higher frequency of drinking were associated with increased odds of fibrosis among patients whose consumption fell below the threshold for heavy alcohol use.

Dr Brooke Rice

"Although the detrimental effects of heavy alcohol use are well accepted, there is no consensus guideline on how to counsel patients about how non-heavy alcohol use may affect liver health," Brooke Rice, MD, an internal medicine resident at Boston University School of Medicine, told Medscape Medical News.

"Current terminology classifies fatty liver disease as either alcoholic or nonalcoholic," she said. "Our results call this strict categorization into question, suggesting that even non-heavy alcohol use should be considered as a factor contributing to more advanced nonalcoholic fatty liver disease (NAFLD) phenotypes."

The study was published online in Clinical Gastroenterology and Hepatology.

Analyzing Associations

NAFLD and alcohol-related liver disease, which are the most common causes of chronic liver disease worldwide, are histologically identical but distinguished by the presence of significant alcohol use, the study authors write.

Heavy alcohol use, based on guidelines from the American Association for the Study of Liver Diseases, is defined as more than 14 drinks per week for women or more than 21 drinks per week for men.

Although heavy alcohol use is consistently associated with cirrhosis and steatohepatitis, studies of non-heavy alcohol use have shown conflicting results, the authors write. However, evidence suggests that the pattern of alcohol consumption — particularly increased weekly drinking and binge drinking — may be an important predictor, they write.

Rice and colleagues conducted a cross-sectional study of 2629 current drinkers in the Framingham Heart Study who completed alcohol-use questionnaires and vibration-controlled transient elastography between April 2016 and April 2019. They analyzed the association between fibrosis and several alcohol-use measures, including total consumption and drinking patterns, among non-heavy alcohol users whose liver disease would be classified as "nonalcoholic" by current nomenclature.

The research team defined clinically significant fibrosis as a liver stiffness measurement of 8.2 kPa or higher. For at-risk NASH, the researchers used two FibroScan-aspartate aminotransferase (FAST) score thresholds — greater than 0.35 or 0.67 and higher. They also considered additional metabolic factors such as physical activity, body mass index, blood pressure, glucose measures, and metabolic syndrome.

Participants were asked to estimate the frequency of alcohol use (average number of drinking days per week during the past year) and the usual quantity of alcohol consumed (average number of drinks on a typical drinking day during the past year). Researchers multiplied the figures to estimate the average total number of drinks per week.

Among the 2629 current drinkers (53% women, 47% men), the average age was 54 years, 7.2% had diabetes, and 26.9% met the criteria for metabolic syndrome. Participants drank about 3 days per week on average with a usual consumption of two drinks per drinking day, averaging a total weekly alcohol consumption of six drinks.

The average liver stiffness measurement was 5.6 kPa, and 8.2% had significant fibrosis.

At the FAST score threshold of 0.67 or greater, 1.9% of participants were likely to have at-risk NASH, with a higher prevalence in those with obesity (4.5%) or diabetes (9.5%). At the FAST score threshold of greater than 0.35, the prevalence of at-risk NASH was 12.4%, which was higher in those with obesity (26.3%) or diabetes (34.4%).

Overall, an increased total number of drinks per week and higher frequency of drinking days were associated with increased odds of fibrosis.

Almost 17.5% of participants engaged in risky weekly drinking, which was defined as eight or more drinks per week for women and 15 or more drinks per week for men. Risky weekly drinking was also associated with higher odds of fibrosis.

After excluding 158 heavy drinkers, the prevalence of fibrosis was unchanged at 8%, and an increased total of drinks per week remained significantly associated with fibrosis.

In addition, multiple alcohol-use measures were positively associated with a FAST score greater than 0.35 and were similar after excluding heavy alcohol users. These measures include the number of drinks per week, the frequency of drinking days, and binge drinking.

"We showed that non-heavy alcohol use is associated with fibrosis and at-risk NASH, which are both predictors of long-term liver-related morbidity and mortality," Rice said.

Implications for Patient Care

The findings have important implications for both NAFLD clinical trials and patient care, the study authors write. For instance, the US Dietary Guidelines for Americans recommend limiting alcohol use to one drink per day for women and two drinks per day for men.

"Our results reinforce the importance of encouraging all patients to reduce alcohol intake as much as possible and to at least adhere to current US Dietary Guidelines recommended limits," Rice said. "Almost half of participants in our study consumed in excess of these limits, which strongly associated with at-risk NASH."

Additional long-term studies are needed to determine the benefits of limiting alcohol consumption to reduce liver-related morbidity and mortality, the authors write.

Dr Fredrik Åberg

The effect of alcohol consumption on liver health "has been controversial, since some studies have suggested that non-heavy alcohol use can even have some beneficial metabolic effects and has been associated with reduced risk of fatty liver disease, while other studies have found that non-heavy alcohol use is associated with increased risk for liver-related clinical outcomes," Fredrik Åberg, MD, PhD, a hepatologist and liver transplant specialist at Helsinki University Hospital in Finland, told Medscape Medical News.

Åberg wasn't involved with this study but has researched alcohol consumption and liver disease. Among non-heavy alcohol users, drinking more alcohol per week is associated with increased hospitalization for liver disease, hepatocellular carcinoma, and liver-related death, he and colleagues have found.

"We concluded that the net effect of non-heavy drinking on the liver is harm," he said. "Overall, this study by Rice and colleagues supports the recommendation that persons with mild liver disease should reduce their drinking, and persons with severe liver disease (cirrhosis and advanced fibrosis) should abstain from alcohol use."

The study authors are supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, a Doris Duke Charitable Foundation Grant, a Gilead Sciences Research Scholars Award, the Boston University School of Medicine Department of Medicine Career Investment Award, and the Boston University Clinical Translational Science Institute. The Framingham Heart Study is supported in part by the National Heart, Lung, and Blood Institute. The authors and Åberg reported no relevant financial relationships.

CGH. Published online December 7, 2022. Abstract

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.

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