HCC recurrence in HCV-infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs - a post-hoc analysis

Transpl Int. 2020 Aug;33(8):917-924. doi: 10.1111/tri.13621. Epub 2020 May 15.

Abstract

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. 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). 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. Taken together, in HCV-infected 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.

Keywords: Silver Study; direct-acting antiviral agents; hepatitis C virus infection; hepatocellular carcinoma; liver transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular*
  • Hepatitis C* / drug therapy
  • Humans
  • Liver Neoplasms*
  • Liver Transplantation*
  • Neoplasm Recurrence, Local
  • Silver
  • Sirolimus / therapeutic use

Substances

  • Silver
  • Sirolimus