Mechanisms of NAFLD development and therapeutic strategies

• Published in: Nature medicine Vol. 24; no. 7; pp. 908 - 922
• Main Authors: Friedman, Scott L., Neuschwander-Tetri, Brent A., Rinella, Mary, Sanyal, Arun J.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2018; Nature Publishing Group
• Subjects: 631/154/309/2144; 692/308/2779/109; Abnormalities; Animal models; Biomedical and Life Sciences; Biomedicine; Cancer Research; Care and treatment; Cellular signal transduction; Cirrhosis; Clinical trials; Comorbidity; Diabetes mellitus; Diagnosis; Drug development; Drug efficacy; Fatty liver; Gene expression; Genetic aspects; Infectious Diseases; Liver; Liver cancer; Liver cirrhosis; Liver diseases; Medical schools; Metabolic Diseases; Metabolic disorders; Metabolic syndrome; Molecular Medicine; Neurosciences; Review Article; Therapeutic applications; Type 2 diabetes
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-018-0104-9

There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression. Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials.