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

Core Tip: Nonalcoholic fatty liver disease (NAFLD) is a sexual dimorphic disease, and its prevalence worldwide is increasing each year. However, our understanding of sex differences in NAFLD remains insufficient. The incidence in males is significantly higher than that in females, and studies have also revealed significant sex differences in influencing factors, pathophysiology, complications and therapies. This review summarizes the current research progress on sex differences in NAFLD and indicates that whether sex differences in NAFLD can be considered in future research, treatment and prevention is worth exploring.