Sex disparities in liver transplantation for hepatocellular carcinoma: long-term outcomes and recurrence predictors.
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BACKGROUND: With a 2- to 3-fold higher incidence in men, hepatocellular carcinoma (HCC) is the leading indication for liver transplantation (LT). Despite this sex disparity in HCC incidence, the influence of recipient sex on long-term LT outcomes, including HCC recurrence, is not well established. This study investigates the impact of recipient sex on the long-term outcomes following LT for HCC. METHODS: All consecutive patients undergoing LT for HCC between 2005 and 2018 were retrospectively analyzed. Data regarding patient demographics, tumor characteristics, and post-transplant outcomes were collected, and recipients were stratified by sex. Kaplan-Meier analysis was used to assess overall and recurrence-free survival (RFS). Multivariable Cox regression models were then used to determine independent predictors of HCC recurrence within each sex group. RESULTS: Of the 384 adult recipients (mean age was 58.7±8.4 years and mean follow-up of 86.5±51.5 months), 17.2% of patients were female. The main etiology of cirrhosis in the female and male groups was alcohol-related (19.7%, 36.5%), HCV (40.9%, 24.5%) and metabolic dysfunction-associated steatohepatitis (MASH) (10.6%, 12.3%). The Model for End-Stage Liver Disease (MELD) and Child-Pugh scores were similar in both groups. 87.9% and 76.4% of the patients were within the Milan criteria and 95.5% and 91.5% of the patients had an alpha-fetoprotein (AFP) score ≤2 at the time of LT, respectively. The 1-, 3-, 5-, 10- and 15-year survival rates were similar in the male and female groups (91.5%, 81.5%, 72.4%, 57.7% and 44.9% vs. 89.4%, 80.1%, 72.0%, 50.0% and 29.6%, P=0.43). Microvascular invasion was seen in 30.3% and 36.3% of the patients, respectively, P=0.36). Recurrence rates were comparable in female and male groups (19.7% vs. 20.1%, respectively, P=0.94). The 10-year RFS rate was 50.6% in the female group and 54.9% in the male group (P=0.61). CONCLUSIONS: Recipient sex does not impact long-term survival or HCC recurrence after LT. However, sex-specific predictors of HCC recurrence were identified: AFP score >2 and prior hepatectomy in females, and these plus diabetes mellitus and older age in males. Furthermore, female recipients presented with a significantly lower incidence of alcohol-associated cirrhosis as the underlying cause of HCC.