Mechanisms and disease consequences of nonalcoholic fatty liver disease

• Published in: Cell Vol. 184; no. 10; pp. 2537 - 2564
• Main Authors: Loomba, Rohit, Friedman, Scott L., Shulman, Gerald I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.05.2021
• Subjects: Carcinoma, Hepatocellular - pathology; fibrosis; Humans; insulin resistance; lipotoxicity; Liver - pathology; liver cancer; Liver Cirrhosis - pathology; Liver Neoplasms - pathology; metabolism-associated fatty liver disease; Non-alcoholic Fatty Liver Disease - pathology; nonalcoholic steatohepatitis; nonalcoholic steatohepatitis; fibrosis; liver cancer; insulin resistance; lipotoxicity; metabolism-associated fatty liver disease
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2021.04.015

Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Its more advanced subtype, nonalcoholic steatohepatitis (NASH), connotes progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. Here we provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of NAFLD, the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in NASH. Non-alcoholic fatty liver disease is an increasingly massive unsolved human health problem affecting an estimated one billion people globally. Understanding the mechanisms of NAFLD development and progression to life-threatening disease is crucial for developing therapeutic strategies.