Nonalcoholic fatty liver disease: a systematic review

IMPORTANCE: Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation. OBJECTIVES: To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease. EVIDENCE REVIEW: PubMed was queried for published articles through February 28, 2015, using the search terms NAFLD and cirrhosis, mortality, biomarkers, and treatment. A total of 88 references were selected, including 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses. FINDINGS: Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest (