Male Cirrhosis Patients Face Greater Risk of Liver Complications Than Females

New research is shedding light on sex disparities in liver complication risk among patients with cirrhosis, highlighting increased risks of hepatocellular carcinoma (HCC), liver transplantation (LT), and decompensated cirrhosis (DC) among male patients compared with female patients.1

Leveraging data for > 400,000 adult patients from the Merative MarketScan Research Databases, the study found that males had > 100% greater risk of HCC, a 63% greater risk of LT, and a 16% greater risk of DC than females. Of note, the sex difference in the risk of adverse liver events was more pronounced in nonviral cirrhosis than viral cirrhosis.1

“A firm recognition of the scope and degree of sex-based differences in cirrhosis outcomes is required to begin the important work to address and eliminate these disparities,” Jeremy Louissaint, MD, an assistant professor in the department of internal medicine at UT Southwestern Medical Center, wrote in an invited commentary about the research.2 “This impactful study is a major step forward toward achieving sex-based equity in cirrhosis outcomes.”

With the prevalence of cirrhosis projected to increase > 50% by 2030, understanding factors potentially predisposing patients to a heightened risk of adverse outcomes is essential.3 Recognizing the importance of understanding sex disparities for optimizing disease management and promoting health equity, Mindie Nguyen, MD, a transplant hepatologist and professor of medicine at Stanford University, and a team of investigators sought to compare the risk of adverse liver events between male and female patients with cirrhosis.1

To do so, they conducted a population-based retrospective cohort study of adult patients with cirrhosis identified from the Merative MarketScan Research Databases from January 2007 to December 2022. For inclusion, patients were required to have ≥ 1 inpatient or 2 outpatient diagnoses of cirrhosis or its complications based on ICD codes.1

The main outcome was the incidence of adverse liver events, including DC, HCC, and LT. Patients were followed up to the occurrence of the primary outcomes or censored at the insurance enrollment end date, the last follow-up date, or the end of the study period, whichever came first.1

Propensity score matching for age, etiologies of cirrhosis, geographic region, insurance type, specialty type, alcohol use disorder, obesity, baseline status of DC, and Charlson Comorbidity Index score yielded 169,711 pairs of female and male patients with similar baseline characteristics for subsequent analyses of adverse liver event incidence.1

During a total follow-up of 258,178.2 person-years (PYs) for females and 228,004.2 PYs for males, DC was identified in 113,334 females (265,766.1 PYs), HCC in 125,033 females (377,919.8 PYs), and LT in 124,409 females (373,369.7 PYs); among males, 108,790 (236,352.3 PYs) were identified with DC, 121,861 (344,422.4 PYs) with HCC, and 120,931 (338,305.7 PYs) with LT.1

Compared with females, investigators noted males had significantly higher incidence rates per 1000 PYs for 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).1

In a Cox proportional hazards regression analysis, male sex was associated with a 16% higher risk of DC (hazard ratio [HR], 1.16; 95% CI, 1.14-1.19; P <.001), a 63% higher risk of LT (HR, 1.63; 95% CI, 1.54-1.71; P <.001), and a 110% higher risk of HCC (HR, 2.10; 95% CI, 1.96-2.25; P <.001).1

Subgroup analyses stratified by major liver disease etiologies revealed male sex was associated with the greatest 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 infection, but not in patients with HBV except for those with HCC (HR, 1.60; 95% CI, 1.08-2.36; P = .02).1

“Considering the shifting etiologies of cirrhosis from viral to nonviral in recent years, future prevention and surveillance strategies for cirrhosis-related complications should incorporate these sex differences,” Nguyen concluded.1

References

1. Shi Y, Zhang X, Wong T, et al. Sex Differences in Risk of Adverse Liver Events in Patients With Cirrhosis. JAMA Netw Open. 2025;8(7):e2523674. doi:10.1001/jamanetworkopen.2025.23674

2. Spann A, Louissaint J. Sex-Based Disparities in Cirrhosis Outcomes—From Recognition to Action. JAMA Netw Open. 2025;8(7):e2523685. doi:10.1001/jamanetworkopen.2025.23685

3. Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. doi:10.1002/hep.29466