Sex differences in mortality and liver-related events in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Background & aims: Many systematic reviews explore the association of non-alcoholic fatty liver disease (NAFLD) with mortality, but none of them explores sex-based differences in detail. We aimed to assess whether NAFLD is associated with cause-specific mortality, all-cause mortality, and cancer incidence in both men and women.

Methods: The PubMed, Embase, and Medline databases were searched from inception through April 2023 for eligible studies. We separately pooled relative risks (RRs) for men and women using a random effects model. Subsequently, the RRs and 95% CIs (confidence intervals) in each study were used to calculate the women-to-men ratio of RRs (RRR). Furthermore, subgroup analyses were performed to explore the robustness of outcomes. The random-effects model was employed to conduct sensitivity analyses to determine the impact of specific studies on the overall findings.

Results: The meta-analysis included nine cohort studies comprising 557 614 patients with NAFLD were chosen. Women were 44% more likely than men to get cancer among those with NAFLD (RRR: 1.44; 95% CI: 1.02-2.04; p = .039). However, no sex-related differences were observed between NAFLD and all-cause mortality (RRR: 1.06; 95% CI: 0.56-2.01; p = .861), liver-related mortality (RRR: 1.06; 95% CI: 0.02-69.82; p = .977), cardiovascular mortality (RRR: 1; 95% CI: 0.65-1.53; p = .987) and liver cancer (RRR: 0.76; 95% CI: 0.43-1.36; p = .36).

Conclusions: There may be sex variations between NAFLD and the risk of cancer, with the connection being stronger in females than in males.