van Hooff Maria C, de Veer Rozanne C, Karam Vincent, Adam Rene, Taimr Pavel, Polak Wojciech G, Pashtoun Hasina, Murad Sarwa Darwish, Corpechot Christophe, Mirza Darius, Heneghan Michael, Lodge Peter, Oniscu Gabriel C, Thorburn Douglas, Allison Michael, Metselaar Herold J, den Hoed Caroline M, van der Meer Adriaan J
Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, The Netherlands.
European Society for Organ Transplantation, Amsterdam, The Netherlands.
JHEP Rep. 2024 Apr 25;6(8):101100. doi: 10.1016/j.jhepr.2024.101100. eCollection 2024 Aug.
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.
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.
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, 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, 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, 0.001) or death (aHR 0.72, 95% CI 0.59-0.87, 0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, 0.001, and aHR 1.34, 95% CI 1.15-1.56, 0.001, respectively).
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.
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.
他克莫司与肝移植（LT）后原发性胆汁性胆管炎（PBC）复发相关，而这反过来可能降低生存率。本研究旨在评估PBC患者LT后使用的钙调神经磷酸酶抑制剂类型与长期预后之间的关联。
生存分析用于评估欧洲肝移植登记处成年PBC患者中免疫抑制药物与移植物或患者生存之间的关联。纳入1990年至2021年间接受脑死亡后捐赠肝脏移植且至少有1年无事件随访的患者。
总共对3175例PBC患者进行了LT后中位11.4年（IQR 5.9 - 17.9）的随访。2056例（64.8%）患者使用他克莫司（Tac），819例（25.8%）患者使用环孢素。在对受者年龄、受者性别、供者年龄和LT年份进行调整后，与环孢素相比，Tac与移植物丢失风险增加（调整后风险比[aHR] 1.07，95% CI 0.92 - 1.25，P = 0.402）或死亡风险增加（aHR 1.06，95% CI 0.90 - 1.24，P = 0.473）无关。在此模型中，维持使用霉酚酸酯（MMF）与较低的移植物丢失风险（aHR 0.72，95% CI 0.60 - 0.87，P = 0.001）或死亡风险（aHR 0.72，95% CI 0.59 - 0.87，P = 0.001）相关，而使用类固醇时这些风险更高（分别为aHR 1.31，95% CI 1.13 - 1.52，P = 0.001和aHR 1.34，95% CI 1.15 - 1.56，P = 0.001）。
在这个大型肝移植登记研究中，钙调神经磷酸酶抑制剂类型与长期移植物或受者生存无关，这为PBC人群LT后使用Tac提供了安心依据。使用MMF的患者移植物丢失和死亡风险较低，表明Tac与MMF联合治疗的阈值应较低。
本研究调查了脑死亡后捐赠肝脏移植后免疫抑制药物与原发性胆汁性胆管炎（PBC）患者长期生存之间的关联。虽然他克莫司此前与PBC复发风险较高相关，但在欧洲肝移植登记处接受PBC移植的患者中，钙调神经磷酸酶抑制剂类型与移植物或患者生存无关。此外，维持使用霉酚酸酯与较低的移植物丢失和死亡风险相关，而维持使用类固醇时这些风险更高。我们的研究结果应为医生在PBC人群肝移植后继续使用Tac提供安心依据，并提示霉酚酸酯联合治疗可能有益。
