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IMPORTANCE: Nonalcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide and is associated with obesity. Weight loss may improve biomarkers of liver disease, but its implications have not been systematically reviewed and quantified. OBJECTIVE: To estimate the association of weight loss interventions with biomarkers of liver disease in NAFLD. DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science databases along with 3 trial registries were searched from inception through January 2019. STUDY SELECTION: Randomized clinical trials of people with NAFLD were included if they compared any intervention aiming to reduce weight (behavioral weight loss programs [BWLPs], pharmacotherapy, and surgical procedures) with no or lower-intensity weight loss intervention. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the studies, extracted the data, and assessed the risk of bias using the Cochrane tool. Pooled mean differences or odds ratios (ORs) were obtained from random-effects meta-analyses. MAIN OUTCOMES AND MEASURES: Blood, radiologic, and histologic biomarkers of liver disease. RESULTS: Twenty-two studies with 2588 participants (with a mean [SD] age of 45 [14] years and with approximately 66% male) were included. Fifteen studies tested BWLPs, 6 tested pharmacotherapy, and 1 tested a surgical procedure. The median (interquartile range) intervention duration was 6 (3-8) months. Compared with no or lower-intensity weight loss interventions, more-intensive weight loss interventions were statistically significantly associated with greater weight change (-3.61 kg; 95% CI, -5.11 to -2.12; I2 = 95%). Weight loss interventions were statistically significantly associated with improvements in biomarkers, including alanine aminotransferase (-9.81 U/L; 95% CI, -13.12 to -6.50; I2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; 95% CI, -2.27 to -0.70; I2 = 94%), histologic NAFLD activity score (-0.92; 95% CI, -1.75 to -0.09; I2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI, -0.54 to 0.27; I2 = 68%). Twelve studies were at high risk of bias in at least 1 domain. In a sensitivity analysis of the 3 trials at low risk of bias, the estimates and precision of most outcomes did not materially change. CONCLUSIONS AND RELEVANCE: The trials, despite some heterogeneity, consistently showed evidence of the association between weight loss interventions and improved biomarkers of liver disease in NAFLD in the short to medium term, although evidence on long-term health outcomes was limited. These findings appear to support the need to change the clinical guidelines and to recommend formal weight loss programs for people with NAFLD.

Original publication




Journal article


JAMA Intern Med

Publication Date





1262 - 1271