Mechanisms and disease consequences of nonalcoholic fatty liver disease

Rohit Loomba; Scott L Friedman; Gerald I Shulman

doi:10.1016/j.cell.2021.04.015

Mechanisms and disease consequences of nonalcoholic fatty liver disease

Cell. 2021 May 13;184(10):2537-2564. doi: 10.1016/j.cell.2021.04.015.

Authors

Rohit Loomba¹, Scott L Friedman², Gerald I Shulman³

Affiliations

¹ NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: roloomba@ucsd.edu.
² Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: scott.friedman@mssm.edu.
³ Departments of Internal Medicine and Cellular & Molecular Physiology, Yale Diabetes Research Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: gerald.shulman@yale.edu.

PMID: 33989548
DOI: 10.1016/j.cell.2021.04.015

Abstract

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.

Keywords: fibrosis; insulin resistance; lipotoxicity; liver cancer; metabolism-associated fatty liver disease; nonalcoholic steatohepatitis.

Publication types

Review
Comment

MeSH terms

Carcinoma, Hepatocellular* / pathology
Humans
Liver / pathology
Liver Cirrhosis / pathology
Liver Neoplasms* / pathology
Non-alcoholic Fatty Liver Disease* / pathology