Several factors have been associated with a high risk of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence and to guide surveillance strategies and adjuvant therapy after LT. In this multi-center study, we aimed to develop a recurrence risk index (RRI) for patients with HCC meeting Milan criteria by imaging at LT. The study cohort included 721 patients who underwent LT between June 2002 and June 2013 at 3 centers. Median time from HCC diagnosis to LT was 8.3 months (IQR 4.1-14.2) and 92% received at least one pre-LT local-regional treatment. Alpha-fetoprotein (AFP) at LT was 20-99 in 19%, 100-999 in 10%, and >1000 in 2%. On explant, 28% had complete tumor necrosis and 22% were outside of Milan criteria. Median post-LT follow-up was 4.3 years and 84 patients (12%) developed HCC recurrence at a median of 12.9 months (IQR 5.0-26.8) after LT. Cumulative probabilities of HCC recurrence at 1 and 5 years were 6% and 13%, respectively. On multivariate Cox proportional hazards regression, three variables independently predicted HCC recurrence: micro-vascular invasion (MVI), AFP at LT, and the sum of the largest viable tumor diameter and number of viable tumors on explant. The RRI was created using these 3 variables, with scores ranging from 0 to ≥5 that were highly predictive of HCC recurrence (Harrell's c-statistic 0.77) (Table 1). The RRI was able to stratify 5 year post-LT recurrence risk ranging from <3% in those with a risk score of 0 and >75% with a risk score of ≥5 (Table 2). In conclusion, we developed a simple and novel RRI for predicting individual HCC recurrence risk after LT. This RRI may have important implications for post-LT HCC surveillance strategies and help identify patients who would derive the most benefit from adjuvant therapies.

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