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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.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.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.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.