Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma

作者：Edward Kenneth Geissler, Andreas Anton Schnitzbauer, C. Zülke, Philipp Edmund Lamby, Andrea Proneth, Christophe Duvoux, Patrizia Burra, Karl‐Walter Jauch, Markus Rentsch, Tom M. Ganten, Jan Schmidt, Utz Settmacher, Michael Heise, Giorgio Ettore Rossi, Umberto Cillo, Norman M. Kneteman, René A. Adam, Bart van Hoek, Philippe Bachellier, Philippe Wolf, Lionel P. E. Rostaing, Wolf O. Bechstein, Magnus Rizell, James J. Powell, Ernest L. Hidalgo, Jean Gugenheim, Heiner H. Wolters, Jens Gunther Brockmann, André Roy, Ingrid Mutzbauer, Angela Schlitt, Susanne Beckebaum, Christian Graeb, Silvio Nadalin, Umberto Valente, Víctor Sánchez Turrión, Neville V. Jamieson, Tim Scholz, M. Colledan, Fred Fändrich, Thomas Becker, Gunnar Söderdahl, Olivier Chazouillères, Heikki Mäkisalo, Georges‐Philippe Pageaux, Rudolf Steininger, Thomas Soliman, Koert Pieter de Jong, Jacques Pirenne, Raimund Margreiter, Johann Pratschke, Antonio D. Pinna, Johann Hauss, Stefan Schreiber, Simone Irene Strasser, Jurgen L. Klempnauer, Roberto Ivan Troisi, Sherrie Bhoori, Jan Paul Lerut, Itxarone Bilbao, Christian Georg Klein, Alfred Königsrainer, Darius F. Mirza, Gerd Otto, Vincenzo Mazzaferro, P. Neuhaus, Hans Jürgen Schlitt · 发表于：Transplantation · 年份：2015 · DOI：10.1097/tp.0000000000000965 · 被引用次数：432 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Organ Transplantation Techniques and Outcomes、Liver physiology and pathology

BACKGROUND: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). METHODS: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. RESULTS: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy p...