Risk and severity of NAFLD differ in men and women

Women have a significantly lower risk of developing nonalcoholic fatty liver disease (NAFLD) but a higher risk of developing advanced fibrosis from NAFLD, according to a systematic review and meta-analysis.

While women have a lower risk of developing nonalcoholic fatty liver disease (NAFLD) than men, those who do have the disease are more likely than men to develop severe consequences, particularly as they age, a recent analysis found.

A systematic review and meta-analysis looked at 54 studies with more than 60,000 patients to determine the relationship between sex and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis. Results were published by Clinical Gastroenterology and Hepatology on April 30.

The analysis found that, in the general population, women had a 19% lower risk of NAFLD than men (pooled risk ratio [RR], 0.81; 95% CI, 0.68 to 0.97), a similar risk of NASH (RR, 1.00; 95% CI, 0.88 to 1.14), and a 37% higher risk of advanced NAFLD fibrosis (RR, 1.37; 95% CI, 1.12 to 1.68). The difference between the sexes was modified by age, with women ages 50 years or older having significantly increased risks of NASH (RR, 1.17; 95% CI, 1.01 to 1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36 to 1.80) than men, and younger patients showing no significant differences by sex.

The change in sex differences with aging fits well with the current understanding of the disease, the study authors noted. “While men tend to accumulate adipose tissue centrally throughout their lifetime, adipose tissue distribution changes over the lifetime of women and is subject to estrogen exposure,” they wrote. The analysis also found some geographic differences—specifically, higher NASH prevalence in East Asian women than men, but not in other parts of the world.

The results have clinical implications, according to the authors. “Thus, women with NAFLD should be evaluated for NASH and fibrosis as vigorously as men. It is further possible that women with NAFLD, particularly those over 50 years of age, may require greater clinical vigilance to diagnose advanced fibrosis compared to men,” they said. The findings also provide potentially useful information for counseling patients and predicting future disease burden, they added.

The authors did caution that the analysis had a number of limitations, including the heterogeneity of the included studies, lack of data to explore potential interactions between body weight and sex, and the possibility that the findings are due to unmeasured factors such as polycystic ovarian syndrome, behavior, or cumulative effects of hormonal therapies, pregnancies, and related complications on women's health.