HCC recurrence in HCV patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs.

BACKGROUND: Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV(+) subgroup of patients from the randomized controlled, international SiLVER Study. METHODS: We performed a post-hoc analysis of 166 HCV(+) SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n=88) received mTOR inhibitor (mTORi)-free, calcineurin inhibitor (CNI)-based versus sirolimus-based immunosuppression (group B: n=78). RESULTS: We found no significant difference regarding HCV-RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus-based immunosuppression + CNIs for >50% (B1; n=44) or <50% (B2; n=34) of the time. While there remained no difference in HCV-RNA titer between groups, HCC recurrence-free survival in group B1 (81.8%) was markedly better versus both group A (62.7%; P=0.0136) and group B2 (64.7%; P=0.0326); Interestingly, further subgroup analysis revealed an increase (P=0.0012) in liver-enzyme values in group B2. CONCLUSION: In HCV patients with HCC and LTx, mTORi immunosuppression + CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV(+) subgroup.