Rinella · JAMA 2015 · systematic review · n=88 studies

Nonalcoholic fatty liver disease: a systematic review.

Cited 2324 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review including randomized clinical trials and meta-analyses

PubMed 26057287 · doi:10.1001/jama.2015.5370 · record verified 2026-08-26

What was done

A systematic review was conducted by querying PubMed through February 28, 2015, using search terms related to nonalcoholic fatty liver disease (NAFLD), cirrhosis, mortality, biomarkers, and treatment. The authors synthesized evidence from 88 selected references, which included 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses.

What was found

NAFLD and its subtype nonalcoholic steatohepatitis (NASH) affect roughly 30% and 5% of the US population, respectively (75 million to 100 million individuals). In patients with NASH, 50% of deaths are due to cardiovascular disease and malignancy. An estimated 66% of individuals older than 50 years with diabetes or obesity have NASH with advanced fibrosis. Identifying the NASH subtype requires liver biopsy, but biomarkers for advanced fibrosis are increasingly reliable. Lifestyle modification is the primary treatment foundation. Pharmacotherapies with proven benefit (vitamin E, pioglitazone, obeticholic acid) showed modest effect sizes (<50%) and lacked FDA approval for this indication. Up to 50% of NAFLD-related hepatocellular carcinoma cases may occur without cirrhosis.

Why it matters

This review provides an evidence-based roadmap for clinicians to risk-stratify patients with NAFLD and highlights that cardiovascular disease and malignancy drive more mortality than liver disease alone in NASH.

Limits

The literature search was restricted to a single database (PubMed) through February 2015. The review aggregates heterogeneous study designs (observational and interventional), and causality between NASH and cardiovascular disease remains unconfirmed by prospective controlled trials.

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