JHEP Reports (Aug 2024)

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis – an ELTR study

  • Maria C. van Hooff,
  • Rozanne C. de Veer,
  • Vincent Karam,
  • Rene Adam,
  • Pavel Taimr,
  • Wojciech G. Polak,
  • Hasina Pashtoun,
  • Sarwa Darwish Murad,
  • Christophe Corpechot,
  • Darius Mirza,
  • Michael Heneghan,
  • Peter Lodge,
  • Gabriel C. Oniscu,
  • Douglas Thorburn,
  • Michael Allison,
  • Herold J. Metselaar,
  • Caroline M. den Hoed,
  • Adriaan J. van der Meer,
  • Darius Mirza,
  • Michael Heneghan,
  • Peter Lodge,
  • Gabriel Oniscu,
  • Douglas Thorburn,
  • Michael Allison,
  • Johann Pratschke,
  • Derek Manas,
  • William Bennet,
  • Pal-Dag Line,
  • Emir Hot,
  • Krzysztof Zieniewicz,
  • Bo Goran Ericzon,
  • Jiri Fronek,
  • Jurgen L. Klempnauer,
  • Allan Rasmussen,
  • Renato Romagnoli,
  • Petr Nemec,
  • Arno Nordin,
  • Andreas Paul,
  • Paolo De Simone,
  • R.J. Porte,
  • Gabriela Berlakovich,
  • Daniel Cherqui,
  • Jacques Pirenne,
  • Etienne Sokal,
  • Giorgio Rossi,
  • Daniel Candinas,
  • Philippe Bachellier,
  • Oleg Rummo,
  • Karim Boudjema,
  • Anna Mrzljak,
  • Olivier Soubrane,
  • Herold Metselaar,
  • Stefan Schneeberger,
  • Francis Navarro,
  • Thierry Berney,
  • Christophe Duvoux,
  • Michele Colledan,
  • Luciano De Carlis,
  • Olivier Boillot,
  • Jean Hardwigsen,
  • Francois Rene Pruvot,
  • Bertrand Suc,
  • Marco Vivarelli,
  • Pierre Alain Clavien,
  • Hauke Lang,
  • Maciej Kosieradzki,
  • Frederik Berrevoet,
  • Bruno Heyd,
  • Matteo Cescon,
  • Laurence Chiche,
  • Eberhard Kochs,
  • Umberto Baccarani,
  • Olivier Detry,
  • Michael Bartels,
  • Massimo Rossi,
  • Olivier Soubrane,
  • Olivier Scatton,
  • Vasileios Papanikolaou,
  • Ian Alwayn,
  • Peter Schemmer,
  • N. Senninger,
  • Christian Ducerf,
  • Fabrizio Di Benedetto,
  • Giuseppe Tisone,
  • Silvio Nadalin,
  • Zoltan Mathe,
  • Marija Ribnikar,
  • Utz Settmacher,
  • Thomas Becker,
  • Nuno Silva,
  • Jorge Daniel,
  • Irinel Popescu,
  • Valerio Lucidi,
  • Wolf O. Bechstein,
  • Thomas Decaens,
  • Jean Gugenheim,
  • Salvatore Gruttadauria,
  • Frausto Zamboni,
  • Murat Zeytunlu,
  • Jorg C. Kalff,
  • Toomas Vali,
  • Yaman Tokat,
  • Ernst Klar,
  • Eberhard Kochs,
  • Renato Romagnoli,
  • Julius Janek,
  • Murat Kilic,
  • Krum Katzarov,
  • Lutz Fisher,
  • Emmanuel Buc,
  • Marco Castagneto,
  • Tarkan Unek,
  • Lubomir Spassov,
  • Dirk Stippel,
  • Christiane Bruns,
  • Hans Schlitt,
  • Ephrem Salame,
  • Piotr Kalicinski,
  • Koray Acarli

Journal volume & issue
Vol. 6, no. 8
p. 101100

Abstract

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Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p <0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p <0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p <0.001, and aHR 1.34, 95% CI 1.15-1.56, p <0.001, respectively). Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that the threshold for combination treatment with Tac and MMF should be low. Impact and implications:: This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.

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