| Sumario: | Tremendous effort has been put forth over the past 2 decades in understanding the pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH). Although multiple potential targets for drug development exist, there have been no approved therapies for NAFLD/NASH. Lipotoxicity, owing to increased delivery of fatty acids to the liver, and hepatic de novo lipogenesis are key drivers of disease pathogenesis. Moreover, genetics, environmental factors, and comorbid conditions converge to determine disease progression in individual patients. Given the complexity and heterogeneity of disease pathogenesis, numerous therapeutic targets have emerged and have been tested in clinical trials. Early trial failures have provided key lessons and foundational insights to move the field forward. Current ongoing phase 3 trials and emerging phase 2 trials are reasons for optimism, and 2 drugs, obeticholic acid and resmetirom, are being evaluated for accelerated approval by the US Food and Drug Administration this year. This article highlights key features of NASH pathophysiology and drug targets, the lessons learned from completed trials, and the current landscape of phase 2 and 3 clinical trials in NASH.
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