There is dearth of studies regarding pathophysiology of gender differences in the incidence, natural history, and outcomes of common liver diseases. It is evident that various potential mechanisms are responsible for these gender difference such as the effect of sex hormones on oxidative and metabolic pathways, differential gene transcription in response to injury, and sex differences in immune regulation. Thus, these differences in turn, can cause variations in access to care and treatment, along with diagnostic considerations in liver disease.

Women, in comparison to men are frequently affected by toxin-mediated liver disease, such as alcohol- and drug-induced liver disease. In addition, they have an increased prevalence of drug-induced hepatotoxicity and acute liver failure than men. This is attributed to the higher susceptible of women to the toxic effects of alcohol on the liver for any given dose of alcohol. Besides, women with alcoholic liver disease have a more rapid progression to fibrosis in women as compared to men.

It has been estimated that women are 10 times more prone to have primary biliary cirrhosis (PBC) than men and have 4 times more probability to be affected with autoimmune hepatitis. Although the appropriate mechanism of gender differences in autoimmune liver disease and autoimmunity is not yet understood, both immunogenetics and sex hormones have a complex and interactive role. Sex steroids is known to impact the immune system by regulating gene expression through steroid-responsive elements, by modifying antigen presentation through effects on human leukocyte antigen genes, and by altering the cytokine environment.  Apart from these changes, X chromosome monosomy and fetal microchimerism also play a role in the pathogenesis of PBC. 

In regard to tumors, majority of benign liver tumors such as cavernous hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, biliary cystadenoma, and solitary hepatic cysts are more common in women whereas malignant tumors are more common in men. Various hypothesis suggest that estrogen levels are associated with benign liver tumors, however, the underlying mechanism implicated is still unclear. 

There are controversial data on gender variation in nonalcoholic fatty liver disease (NAFLD), which exhibits a wide spectrum of manifestations, such as steatosis, steatohepatitis, and cirrhosis. However, certain studies support the finding that women are less commonly affected by NALFD. It is most commonly encountered in men and postmenopausal women who have not received hormone replacement therapy, suggestive of important role of sex hormones, especially estrogen in the pathogenesis of NAFLD. Besides, women have higher rate of acute hepatitis C virus (HCV) infection than men.

Source: Guy J, Peters MG. Liver disease in women: the influence of gender on epidemiology, natural history, and patient outcomes. Gastroenterol Hepatol (N Y). 2013;9(10):633-639.