Nonalcoholic fatty liver disease shows significant sex dimorphism

Abstract

Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.

Keywords: Cirrhosis; Estrogen; Metabolic dysfunction-associated fatty liver disease; Nonalcoholic fatty liver disease; Sex differences; Steatosis.