Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis

doi:10.1016/j.cgh.2018.01.026

Clinical Gastroenterology and Hepatology

Volume 16, Issue 9, September 2018, Pages 1511-1520.e5

https://doi.org/10.1016/j.cgh.2018.01.026 Get rights and content

Background & Aims

Cross-sectional studies of patients with nonalcoholic fatty liver disease (NAFLD) have reported a lower prevalence of severe disease among modest drinkers compared with nondrinkers. We collected data from adult participants in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network to evaluate the longitudinal association between modest use of alcohol and histology findings in patients with NAFLD, using paired liver biopsies collected more than 1 year apart.

Methods

We studied NASH Clinical Research Network participants 21 years or older, not receiving pharmacologic therapy, from whom 2 or more liver biopsies and data on alcohol use within 2 years of the initial biopsy were available. Alcohol consumption was evaluated at study entry using the Alcohol Use Disorders Identification Test and Skinner Lifetime Drinking History questionnaires. At each follow-up visit participants were asked about alcohol use frequency, number of drinks on a typical day, and frequency of heavy drinking. The association between baseline drinking status and changes in fibrosis stage, NASH histology, and the NAFLD Activity Score and its individual components were evaluated by analysis of covariance. The association between change in drinking status and change in histology was evaluated using adjusted logistic regression.

Results

Of 285 participants (82% white, 70% female, mean age, 47 y) meeting entry criteria, 168 (59%) were modest alcohol users (≤2 drinks/d) and the remaining 117 were abstinent. At baseline, a higher proportion of modest alcohol users were white (86% vs 76% nonwhite) (P = .04) and a lower proportion of modest alcohol users were diagnosed with definite NASH (57% vs 74% without NASH; P = .01). During a mean follow-up period of 47 months between biopsies, nondrinkers had a greater mean reduction in steatosis grade (reduction, 0.49) than modest drinkers (reduction, 0.30; P = .04) and a greater reduction in mean level of aspartate transaminase (reduction, 7 U/L vs an increase of 2 U/L in modest drinkers; P = .04). Modest drinkers had significantly lower odds of NASH resolution compared with nondrinkers (adjusted odds ratio, 0.32; 95% CI, 0.11–0.92; P = .04) on adjusted analysis.

Conclusions

In a longitudinal analysis of liver biopsies from patients with NAFLD not receiving pharmacologic therapy, modest alcohol use was associated with less improvement in steatosis and level of aspartate transaminase, as well as lower odds of NASH resolution, compared with no use of alcohol.

Section snippets

Study Design and Participants

This was a longitudinal cohort study of adult participants recruited into the studies conducted by the NASH CRN, a multicenter network sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Participants for this study were drawn from 3 groups within the NASH CRN studies, as follows: (1) the adult NAFLD Database study, (2) adults on placebo in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS)

Characteristics of the Study Population

A total of 285 patients with NAFLD from the NASH CRN trials were included in the analysis. These included 49 placebo recipients from the PIVENS trial, 49 placebo recipients from the FLINT trial, and 187 subjects followed up in the NASH CRN database cohort who did not receive specific pharmacologic therapy for NAFLD. Participants were a mean age of 47.0 years, predominantly female (70%), white (82%), and obese (mean BMI, 34.7 kg/m²). Diabetes (34.4%) and the metabolic syndrome (69.2%) were

Discussion

By using a well-characterized, longitudinal cohort of NAFLD patients with paired liver biopsy specimens an average of 4 years apart, we found that modest alcohol use at baseline was associated with less improvement in steatosis grade and AST level when compared with nondrinkers. Overall, NAFLD activity improved without pharmacologic intervention in the entire cohort and likely was owing to greater attention to healthy lifestyle. Fourteen nondrinkers who became modest drinkers at follow-up

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: Conflicts of interest The authors disclose no conflicts.

: Funding The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713). Additional support has been received from the National Center for Advancing Translational Sciences (grants UL1TR000439, UL1TR000436, UL1TR000006, UL1TR000448, UL1TR000100, UL1TR000004, UL1TR000423, and UL1TR000058). Also supported by the Advanced/Transplant Hepatology Fellowship and the Clinical and Translational Research Award from the American Association for the Study of Liver Diseases Foundation (V.A.). This work also was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute.

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Original articlePancreas, biliary tract, and liverAmong Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design and Participants

Characteristics of the Study Population

Discussion

Gastroenterology

J Hepatol

J Hepatol

J Hepatol

Contemp Clin Trials

Lancet

Gastroenterology

Alcohol consumption and mortality among middle-aged and elderly U.S. adults

N Engl J Med

Variant in PNPLA3 is associated with alcoholic liver disease

Nat Genet

Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

Nat Genet

Gut microbiota produce alcohol and contribute to NAFLD

Gut

Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial

JAMA

Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals

Gut

Original article
Pancreas, biliary tract, and liver
Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis