Sex disparities in liver transplantation for hepatocellular carcinoma: long-term outcomes and recurrence predictors.

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.