Pathogenetic Pathways in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD)-a condition of excess fat accumulation in hepatocytes associated with metabolic dysfunction-has surpassed viral hepatitis to become the most prevalent chronic liver disease worldwide. As of now, only modestly effective pharmacological therapies for NAFLD exist. The uncomplete understanding of the pathophysiology underlying the heterogeneous disease spectrum known as NAFLD remains one of the major obstacles to the development of novel therapeutic approaches. This review compiles current knowledge on the principal signaling pathways and pathogenic mechanisms involved in NAFLD, which are analyzed in relation to its main pathological hallmarks (ie, hepatic steatosis, steatohepatitis, and liver fibrosis).