Women have a lower overall risk of acquiring nonalcoholic fatty liver disease (NAFLD) than men do. Yet, once NAFLD is established, women have increased risk of advanced fibrosis — especially after reaching 50 years of age, according to a report published in Clinical Gastroenterology and Hepatology.

NAFLD is the second leading indication for liver transplant and now accounts for a substantial proportion of hepatocellular carcinoma incidences. There is a substantial gender disparity in the prevalence and severity of many chronic liver diseases; however, the effect of gender on the risk and clinical course of NAFLD remains unclear.

Researchers conducted a systematic review and meta-analysis of all observational studies investigating NAFLD prevalence or severity (defined as histologic NASH or advanced fibrosis) in adults (age ≥18 years) to determine if any gender differences existed. They identified a total of 54 studies reporting sex-stratified NAFLD prevalence in 62,239 population-based samples and either NASH (n=5428) or advanced fibrosis (n=6444) in patients with biopsy-proven NAFLD from MEDLINE, EMBASE, and Cochrane databases from inception of each database through December 2017. Extracted data included study characteristics, method of NAFLD diagnosis or histologic assessment, study population characteristics, demographic characteristics, clinical characteristics (BMI, T2DM or IGT), and liver disease severity when relevant. Pooled relative risk ratios were calculated comparing women with men for each outcome.

The analysis revealed that the pooled overall NAFLD prevalence was 26.3% (95% CI, 21.4%-31.9%; I²=100%). Notably, women had a 19% lower risk of NAFLD compared with men in the general population with a (pooled risk ratio [RR] 0.81, 95% CI, 0.68-0.97, I² 97.5%). No significant difference was found in the prevalence of NASH between women and men with biopsy-proven NAFLD (RR, 1.00; 95% CI, 0.88–1.14; I², 85.1%). Additionally, women had 37% higher pooled prevalence of advanced fibrosis than men (RR, 1.37; 95% CI, 1.12–1.68; I², 74.0%). When performing a subgroup analysis by age on NAFLD severity, NASH prevalence was 17% higher in women compared with men with NASH (RR, 1.17; 95% CI, 1.01–1.36) in study populations with average ages of 50 years or more. Similarly, advanced fibrosis prevalence was 56% higher in women than men (RR, 1.56; 95% CI, 1.36–1.80; I²=0). No significantly differences were observed for NASH and advanced fibrosis risks between men and women in study populations with average ages of <50 years.

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Limitations include significant heterogeneity among the studies investigated, and confounders such as the interaction between body weight and gender, other health issues and behavioral factors.

“These findings have far-reaching implications for the future burden of liver disease, women’s health and gender disparities in liver disease,” the authors concluded.

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Reference

Balakrishnan M, Patel P, Dunn-Valadez S, et al. Women have lower risk of nonalcoholic fatty liver disease but higher risk of progression vs men: A systematic review and meta-analysis (published online April 30, 2020). Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2020.04.067