HCC recurrence in HCV‐infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post‐hoc analysis. (15th May 2020)

• Record Type: Journal Article
• Authors: Werner, Jens M.; Hornung, Matthias; Krah, Rubertha; Götz, Markus; Schnitzbauer, Andreas A.; Schlitt, Hans J.; Geissler, Edward K.
• Other Names: Zülke Carl investigator.; Lamby Philipp E. investigator.; Proneth Andrea investigator.; Duvoux Christophe investigator.; Burra Patrizia investigator.; Jauch Karl‐Walter investigator.; Rentsch Markus investigator.; Ganten Tom M. investigator.; Schmidt Jan investigator.; Settmacher Utz investigator.; Heise Michael investigator.; Rossi Giorgio investigator.; Cillo Umberto investigator.; Kneteman Norman investigator.; Adam René investigator.; Hoek Bart investigator.; Bachellier Philippe investigator.; Wolf Philippe investigator.; Rostaing Lionel investigator.; Bechstein Wolf O. investigator.; Rizell Magnus investigator.; Powell James investigator.; Hidalgo Ernest investigator.; Gugenheim Jean investigator.; Wolters Heiner investigator.; Brockmann Jens investigator.; Roy André investigator.; Mutzbauer Ingrid investigator.; Schlitt Angela investigator.; Beckebaum Susanne investigator.; Graeb Christian investigator.; Nadalin Silvio investigator.; Valente Umberto investigator.; Turrión Victor Sánchez investigator.; Jamieson Neville investigator.; Scholz Tim investigator.; Colledan Michele investigator.; Fändrich Fred investigator.; Becker Thomas investigator.; Söderdahl Gunnar investigator.; Chazouillères Olivier investigator.; Mäkisalo Heikki investigator.; Pageaux Georges‐Philippe investigator.; Steininger Rudolf investigator.; Soliman Thomas investigator.; Jong Koert P. investigator.; Pirenne Jacques investigator.; Margreiter Raimund investigator.; Pratschke Johann investigator.; Pinna Antonio D. investigator.; Hauss Johann investigator.; Schreiber Stefan investigator.; Strasser Simone investigator.; Klempnauer Jürgen investigator.; Troisi Roberto I. investigator.; Bhoori Sherrie investigator.; Lerut Jan investigator.; Bilbao Itxarone investigator.; Klein Christian G. investigator.; Königsrainer Alfred investigator.; Otto Gerd investigator.; Mazzaferro Vincenzo investigator.; Neuhaus Peter investigator.;
• Is Part Of: Transplant international. Volume 33:Number 8(2020)
• Page Start: 917
• Page End: 924
• Publication Date: 2020-05-15
• Subjects: direct‐acting antiviral agents -- hepatitis C virus infection -- hepatocellular carcinoma -- liver transplantation -- Silver Study; Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.13621
• Languages: English
• ISSNs: 0934-0874

Abstract

Summary: 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.