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.

Protective effects of baicalin magnesium on non-alcoholic steatohepatitis rats are based on inhibiting NLRP3/Caspase-1/IL-1β signaling pathway

“…Liver lipid deposition induces an inflammatory response, and inflammation also further leads to liver damage, lipid deposition, and oxidative stress [ 43 ]. MPO can cause peroxidation at the site of liver inflammation, leading to hepatocyte damage [ 44 ]. ALT and AST are common indicators of liver injury.…”

Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

“…Furthermore, extensive literature suggests that chronic liver disease is influenced by sexual dimorphism. Recent studies have revealed significant differences between men and women in the prevalence, risk factors, pathophysiology, complications and treatments of NAFLD [ 17 , 47 , 48 ]. HCC is the fifth most common malignancy in men and the eighth in women [ 47 , 48 ].…”

“…Compared to women, men have a higher incidence of NAFLD, exhibit greater accumulation of visceral fat, experience more severe liver fibrosis and have a higher incidence of liver cancer. Furthermore, once NAFLD occurs, women show more rapid progression of liver fibrosis and higher levels of liver cell damage and inflammation [ 17 , 49 ]. However, despite the evidence in the literature, the underlying molecular mechanisms of sexual dimorphism in NALFD are not clear.…”

“…In this regard, in recent years, several reports have suggested that sex-specific fat distribution could be one of the determining factors that could explain, at least in part, the different incidence of HCC between both sexes [ 17 ], as adiposity-related liver diseases increasingly emerge as the most common cause of chronic liver disease. In addition, it is known that the main cause of HCC is NAFLD associated with obesity [ 18 , 19 , 20 , 21 ], which is the most common form of chronic liver disease globally, affecting approximately 25–30% of the general population [ 22 ], 58% of individuals who are overweight and up to 90% of patients with obesity [ 20 , 23 , 24 ].…”

Current status of disparity in liver disease

“…While this suggests that estrogen may play a protective role in NAFLD, a longer duration of estrogen has been shown to increase the likelihood of NALFD development[ 33 ]. Women may also be at risk of faster liver fibrosis progression than men[ 34 ]. Furthermore, lower total testosterone level has been associated with severe NAFLD in men[ 35 , 36 ].…”