Clinical Impact of Sexual Dimorphism in Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH)

Patrizia Burra; Debora Bizzaro; Anna Gonta; Sarah Shalaby; Martina Gambato; Maria Cristina Morelli; Silvia Trapani; Annarosa Floreani; Fabio Marra; Maurizia Rossana Brunetto; Gloria Taliani; Erica Villa


Liver International. 2021;41(8):1713-173. 

In This Article

Abstract and Introduction


NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.


Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are leading cause of liver disease and liver transplantation (LT) worldwide.[1,2] NAFLD/NASH are sex-dimorphic diseases, with a general higher prevalence in men.[3] However, protective effect observed in fertile women seems to be lost after menopause. Thus, consideration on sex and hormonal status related to age (puberty, menopause) is critical in defining risk factors, disease prevention and treatment of NAFLD.[4]

Despite many of the major risk factors for NAFLD, including metabolic syndrome (MS), type 2 diabetes mellitus (T2DM) and regional adiposity, are known to present clear and profound sex dimorphism, fewer publications describe sex differences in NAFLD, compared to other areas of medicine.

An appropriate attention to biological sex differences, age, hormonal status, but also gender differences, including dietary patterns, exercise and quality of life should be equally considered in the assessment of NAFLD.[5] This consideration will lead to a better understanding of sex differences in NAFLD and NASH, and will aid in achieving sex-specific personalized treatments and therapies.[6,7]

In this review, we summarize the main current findings about the influence of sex and gender on epidemiology, pathogenesis, disease progression, indication for LT and treatments.