Role of sex in liver tumor occurrence and clinical outcomes: a comprehensive review

Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient's sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender-based differences in the molecular mechanisms associated with liver carcinogenesis and the prevalence, prognosis, and treatment of primary and metastatic liver tumors.

Automated summary

Clinical research has shown that liver diseases can develop, progress, and respond to treatment differently in men and women due to the presence of estrogen and androgen receptors, which result in disparities in gene expression patterns, immune responses, and liver damage progression. Hormones and certain lifestyle factors like obesity, alcohol consumption, and smoking can interact with hormone-related mechanisms to affect liver diseases. The impact of sex hormones and gender differences on liver tumor occurrence and clinical outcomes remains uncertain. In this review, we critically examine gender-based differences in molecular mechanisms associated with liver carcinogenesis and the prevalence, prognosis, and treatment of liver tumors.