Sex differences in hepatic encephalopathy: addressing the knowledge gap

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portal-systemic shunting with a significant impact on patients' quality of life and healthcare systems. This narrative review was elaborated by the Special Interest Group (SIG) "Gender in Hepatology" of the Italian Association for the Study of the Liver (AISF) and addresses the underexplored area of sex differences in HE, examining epidemiological trends, clinical manifestations and potential underlying mechanisms. Current evidence suggests that men and women may experience different prevalence rates, risk factors and disease progression due to biological and psychosocial factors. However, these differences remain poorly understood, with limited research on sex-specific outcomes, treatment adherence and psychological effects. Emerging data on body composition, gut microbiota and experimental models highlight potential mechanisms contributing to these differences. Given the evolving epidemiology of liver disease, this review highlights the need for targeted studies and sex-specific approaches in the management of HE to advance personalised medicine and improve outcomes.