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Abstract Details
HCC Recurrence in HCV-infected Patients After Liver Transplantation: SiLVER Study Reveals Benefits of Sirolimus in Combination With CNIs - A Post-Hoc Analysis
Jens M Werner1, Matthias Hornung1, Rubertha Krah1, Markus Götz1, Andreas A Schnitzbauer12, Hans J Schlitt1, Edward K Geissler13, International SiLVER study group
Author information
International SiLVER study group:
Carl Zülke, Philipp E Lamby, Andrea Proneth, Christophe Duvoux, Patrizia Burra, Karl-Walter Jauch, Markus Rentsch, Tom M Ganten, Jan Schmidt, Utz Settmacher, Michael Heise, Giorgio Rossi, Umberto Cillo, Norman Kneteman, René Adam, Bart Hoek, Philippe Bachellier, Philippe Wolf, Lionel Rostaing, Wolf O Bechstein, Magnus Rizell, James Powell, Ernest Hidalgo, Jean Gugenheim, Heiner Wolters, Jens Brockmann, André Roy, Ingrid Mutzbauer, Angela Schlitt, Susanne Beckebaum, Christian Graeb, Silvio Nadalin, Umberto Valente, Victor Sánchez Turrión, Neville Jamieson, Tim Scholz, Michele Colledan, Fred Fändrich, Thomas Becker, Gunnar Söderdahl, Olivier Chazouillères, Heikki Mäkisalo, Georges-Philippe Pageaux, Rudolf Steininger, Thomas Soliman, Koert P Jong, Jacques Pirenne, Raimund Margreiter, Johann Pratschke, Antonio D Pinna, Johann Hauss, Stefan Schreiber, Simone Strasser, Jürgen Klempnauer, Roberto I Troisi, Sherrie Bhoori, Jan Lerut, Itxarone Bilbao, Christian G Klein, Alfred Königsrainer, Gerd Otto, Vincenzo Mazzaferro, Peter Neuhaus
Affiliations
1Department of Surgery, University Hospital Regensburg, Regensburg, Germany.
2Department of Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany.
3Division of Personalized Tumor Therapy, Fraunhofer Institute for Experimental Medicine and Toxicology, Regensburg, Germany.
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.