Gender differences in HCC incidence are known, with men at greater risk than women. Pre transplant AFP levels strongly predict post LT HCC recurrence, though gender differences in post LT HCC recurrence and the relative contribution of AFP level by sex are not known. In this UNOS-based cohort study, we investigate potential gender differences in HCC recurrence and predictors of HCC recurrence by sex among LT recipients with HCC MELD exception between 2006-2010. Covariates included race, disease etiology, co-morbidities, AFP at listing and transplant (within 3 months), tumor burden, loco-regional therapy, donor risk index, and post LT mTOR inhibitor use. HCC recurrence by gender was assessed by competing risks models and separately performed among men and women, stratified by AFP at LT. Results: 3872 men and 1130 women (mean age 57 and 59, respectively) were included. HCC recurred in 258 men (7%) and 66 women (6%) at 364 median days (IQR 172-652) post LT. Median AFP at LT was higher in women (14, IQR 6-60) than men (11, IQR 5-41), p< 0.001. Overall, there was no gender difference in HCC recurrence (HR 0.9, 95% CI 0.7-1.2, p=0.4) but when stratified by AFP level, marked gender differences in HCC recurrence were observed (Figure). For AFP levels at LT between 101-500, HCC recurrence was higher in women compared to men (HR 2.3, 95% CI 1.2-4.6, p=0.018). Risk of HCC recurrence was similar between sexes for AFP levels ≤ 100 (HR 0.8, 0.5-1.2, p=0.3). Too few women recurred with AFP levels > 500 to investigate this threshold. Conclusion: Novel gender differences in risk of HCC recurrence are evident, with more than double the risk in women compared to men with AFP levels at LT between 101-500. Our findings may help to explain the wide AFP variability purported to predict post LT recurrence in prior studies and identify a subgroup that may benefit from more intensive post LT surveillance.

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