Targeting FGF21 for the treatment of nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH), the severe stage of nonalcoholic fatty liver disease (NAFLD), is defined as the presence of hepatic steatosis with inflammation, hepatocyte injury, and different degrees of fibrosis. Although NASH affects 2–5% of the global population, no drug has been specifically approved to treat the disease. Fibroblast growth factor 21 (FGF21) and its analogs have emerged as a potential new therapeutic strategy for the treatment of NASH. In fact, FGF21 deficiency favors the development of steatosis, inflammation, hepatocyte damage, and fibrosis in the liver, whereas administration of FGF21 analogs ameliorates NASH by attenuating these processes. We review mechanistic insights into the beneficial and potential side effects of therapeutic approaches targeting FGF21 for the treatment of NASH.