Sex-Based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation

BACKGROUND Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence post-liver transplant. METHODS We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017. RESULTS A total of 12,711 patients underwent liver transplant for HCC: 2,909 (23%) women and 9,802 (73%) men. Women had significantly lower rates of post-liver transplant HCC recurrence than men (4.0 v. 5.4%, p=0.002). A cox-regression analysis for post-liver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein (AFP) at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of post-liver transplant HCC recurrence (95CI 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, AFP, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (p>0.05 for each). CONCLUSIONS This study demonstrates an independent effect of sex on risk for HCC recurrence post-liver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.