Clinical impact of sexual dimorphism in non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH)

Abstract

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.

Gender-specific prevalence of metabolic-associated fatty liver disease among government employees in Tianjin, China: a cross-sectional study

“…Open access in different cohorts. 11 The incidence of MAFLD extent from 19 to 44.5/1000 person-years in Asia, 11 and the prevalence of this condition in China only reaches 29.2%. 12 Moreover, because of the variant obesity rates and the different regional and economic development levels, the prevalence rates are constantly oscillating.…”

“…12 Moreover, because of the variant obesity rates and the different regional and economic development levels, the prevalence rates are constantly oscillating. [11][12][13] In the past 20 years, due to China's rapid economic ascendance, the prevalence of MAFLD in coastal areas has significantly increased with the growth of per capita Gross National Product (GDP). 14 Patients with simple steatosis are prone to develop more severe liver fibrosis and cirrhosis.…”

The advantages of physical exercise as a preventive strategy against NAFLD in postmenopausal women

“…88,89 Therefore, a large amount of FFAs are delivered and accumulated in hepatocytes, a step that increases the risk for NAFLD development. 90,91 In this scenario, NAFLD prevalence increases in postmenopausal women 56 due to expansion of abdominal adiposity and a higher rate of lipolysis in adipose tissue after oestrogen withdrawal. 92 In addition, the regulation of the expression of proteins involved in hepatic lipid management by oestrogens might represent an additional mechanism.…”

“…54 Sexual dimorphism of NAFLD development is not a novelty and has been a frequent topic of several reviews. [54][55][56][57] However, due to alterations in body composition, fat distribution, hormonal and metabolic changes, the predisposition to develop NAFLD increases in women after menopause. [58][59][60] To date, there is no effective intervention for NAFLD, 61 including one developed after menopause.…”

The Role and Mechanism of Oxidative Stress and Nuclear Receptors in the Development of NAFLD

“…The prevalence of NAFLD differs in gender and age [ 119 ]. Premenopausal women are less likely to develop NAFLD than men of the same age.…”