Sex Differences in Risk of Adverse Liver Events in Patients With Cirrhosis.

Importance: Patients with cirrhosis are at high risk of developing adverse liver events. However, data on sex differences are limited. Objective: To compare risk of adverse liver events between male and female patients with cirrhosis. Design, Setting, and Participants: This population-based retrospective cohort study included adult patients with cirrhosis who were identified from a US private health insurance claims database (Merative MarketScan Research Databases) from January 1, 2007, to December 31, 2022. Exposures: Males compared with females. Main Outcomes and Measures: The main outcome was the incidence of adverse liver events (decompensated cirrhosis [DC], hepatocellular carcinoma [HCC], and liver transplant [LT]). Propensity score matching on age, liver disease etiologies, geographic region, insurance type, specialty type, alcohol use disorder, obesity, baseline status of decompensation, and Charlson Comorbidity Index score was used to balance baseline characteristics of the male and female groups. Results: The study included 438 706 patients with cirrhosis (mean [SD] age, 56.8 [15.4] years; 50.8% males), with a higher mean (SD) age in males than in females (57.6 [14.3] vs 55.9 [16.4] years). Propensity score matching yielded 169 711 pairs of female and male patients with similar baseline characteristics for subsequent analyses. Males compared with females had a higher incidence (per 1000 person-years) of DC (65.77 [95% CI, 64.74-66.81] vs 55.35 [95% CI, 54.46-56.25]; P < .001), HCC (6.98 [95% CI, 6.71-7.27] vs 3.35 [95% CI, 3.17-3.54]; P < .001), and LT (10.23 [95% CI, 9.89-10.58] vs 6.27 [95% CI, 6.01-6.52]; P < .001). In the Cox proportional hazards regression model, male sex was associated with 16% higher risk of DC (hazard ratio [HR], 1.16 [95% CI, 1.14-1.19]; P < .001), 63% of LT (HR, 1.63 [95% CI, 1.54-1.71]; P < .001), and 110% of HCC (HR, 2.10 [95% CI, 1.96-2.25]; P < .001). Among the major liver disease etiologies, male sex (compared with female sex) was associated with the highest risk of adverse liver events in patients with alcohol-related liver disease including DC (HR, 1.13 [95% CI, 1.08-1.19]; P < .001), HCC (HR, 2.40 [95% CI, 2.01-2.88]; P < .001), and LT (HR, 1.36 [95% CI, 1.21-1.53]; P < .001), followed by metabolic dysfunction-associated steatotic liver disease and hepatitis C virus (HCV) infection, but not in patients with HBV except for those with HCC (HR, 1.60 [95% CI, 1.08-2.36]; P = .02). Conclusions and Relevance: The findings of this cohort study of adult patients with cirrhosis suggest that significant sex differences in liver complication risk exist, which was more pronounced in nonviral (alcohol-related liver disease and metabolic dysfunction-associated steatotic liver disease) compared with viral (HBV and HCV) cirrhosis. Sex disparities should be taken into consideration in future guidelines and programs for disease monitoring, prevention, and treatment of patients with cirrhosis.