Women Have a Lower Risk of Nonalcoholic Fatty Liver Disease but a Higher Risk of Progression vs Men: A Systematic Review and Meta-analysis

Background & Aims The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis. Methods Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome. Results Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD analysis, 5428 for the NASH analysis, and 6444 for the advanced fibrosis analysis. Women had a 19% lower risk of NAFLD than men in the general population (pooled risk ratio [RR], 0.81; 95% CI, 0.68–0.97; I2 = 97.5%). Women had a similar risk of NASH (RR, 1.00; 95% CI, 0.88–1.14; I2 = 85.1%), and a 37% higher risk of advanced fibrosis (RR, 1.37; 95% CI, 1.12–1.68; I2 = 74.0%) than men. Age modified the effect of sex on NAFLD severity. Risks of NASH (RR, 1.17; 95% CI, 1.01–1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36–1.80; I2 = 0) were substantially higher in women in study populations with average ages of 50 years and older; sex differences in NASH and advanced fibrosis were attenuated in younger populations. Conclusions In a systematic review and meta-analysis, we found women to have a lower risk of NAFLD than men. However, once NAFLD is established, women have a higher risk of advanced fibrosis than men, especially after age 50 years.