Weight loss interventions may improve biomarkers of liver disease in NAFLD

In a meta-analysis of 22 studies in patients with nonalcoholic fatty liver disease (NAFLD), weight loss interventions were associated with improvements in alanine aminotransferase level, liver steatosis, histologic NAFLD activity score, and nonalcoholic steatohepatitis.


Weight loss interventions in patients with nonalcoholic fatty liver disease (NAFLD) may yield improvements in various biomarkers of liver disease, according to a recent study.

Researchers performed a systematic review and meta-analysis to estimate the association of interventions for weight loss and liver disease biomarkers in this population. Randomized clinical trials were included if they involved patients with NAFLD and compared any intervention to reduce weight with no weight loss or a lower-intensity weight loss intervention. The main outcome measures were hematologic, radiologic, and histologic liver disease biomarkers. Results were published by JAMA Internal Medicine on July 1.

Overall, 22 studies with 2,588 participants were included. The mean patient age was 45 years, and about 66% were men. Most of the studies (15 of 22) tested behavioral weight loss programs, six tested pharmacotherapy, and one tested a surgical procedure. Median duration of the interventions was six months. Statistically significant improvements in alanine aminotransferase level (−9.81 U/L; 95% CI, −13.12 to −6.50 U/L), histologically or radiologically measured liver steatosis (standardized mean difference, −1.48; 95% CI, −2.27 to −0.70), histologic NAFLD activity score (−0.92; 95% CI, −1.75 to −0.09), and presence of nonalcoholic steatohepatitis (odds ratio, 0.14; 95% CI, 0.04 to 0.49) were associated with weight loss interventions, although no statistically significant change was seen in histologic liver fibrosis. While 12 of the 22 studies were at high risk for bias in one or more domains, a sensitivity analysis of the three trials at low risk for bias found no material change in most outcomes.

The authors noted that their trial was limited by high statistical heterogeneity and that the pooled behavioral weight loss programs had varying intensity and format of delivery. “Weight loss interventions appeared to be associated with statistically and clinically significant improvements in biomarkers of liver disease in people with NAFLD in the short term,” the authors wrote. “The accumulated evidence supports changing the clinical guidelines and routine practice to recommend formal weight loss programs to treat people with NAFLD.” They called for future trials to examine longer-term follow-up of weight loss interventions, as well as programs that can help patients maintain long-term weight loss.

An accompanying editorial noted that the current study did not find changes in liver fibrosis, which is a major predictor of liver-related mortality, and said that additional research involving long-term follow-up and histologic measurement is needed. However, the editorialists agreed with the study authors' conclusions. “Overall, this study should encourage clinicians—hepatologists and primary care physicians alike—to incorporate weight loss programs into their treatment of NAFLD,” they wrote. “In addition, large-scale support for interventions focused on maintenance of weight loss will be key in trying to curb the impending epidemic of advanced liver disease in NAFLD.”