Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France.
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France.
J Hepatol. 2020 Sep;73(3):559-565. doi: 10.1016/j.jhep.2020.03.043. Epub 2020 Apr 7.
BACKGROUND & AIMS: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT.
We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983-2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10-15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models.
While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28-0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13-0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22-0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49-0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28-3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death.
Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality.
Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes.
原发性胆汁性胆管炎（PBC）在肝移植（LT）后复发较为常见，可损害移植物和患者的生存。熊去氧胆酸（UDCA）是目前治疗 PBC 的标准疗法。我们研究了预防性应用 UDCA 对 LT 后 PBC 复发的发生率和长期后果的影响。
我们对 1983 年至 2017 年间在 16 个中心（9 个国家）接受 PBC 移植的 780 例患者进行了回顾性队列研究，并进行了中位时间为 11 年的随访。其中 190 例接受了预防性 UDCA（10-15mg/kg/天）治疗。主要结局是 PBC 复发的组织学证据。次要结局是移植物丢失、与肝脏相关的死亡和全因死亡。使用多变量调整 Cox 模型和限制性平均生存时间（RMST）模型来量化预防性 UDCA 与结局之间的关系。
虽然 PBC 的复发显著缩短了移植物和患者的生存时间，但预防性应用 UDCA 与 PBC 复发风险降低相关（调整后的危险比[aHR]0.41；95%CI 0.28-0.61；p<0.0001）、移植物丢失（aHR 0.33；95%CI 0.13-0.82；p<0.05）、与肝脏相关的死亡（aHR 0.46；95%CI 0.22-0.98；p<0.05）和全因死亡（aHR 0.69；95%CI 0.49-0.96；p<0.05）。在 RMST 分析中，预防性 UDCA 在 20 年内导致生存获益 2.26 年（95%CI 1.28-3.25）。与预防性 UDCA 联合使用环孢素而不是他克莫司具有互补的保护作用，可降低 PBC 复发和全因死亡的累积发生率。
LT 后预防性应用 UDCA 可降低 PBC 复发、移植物丢失和死亡的风险。联合应用环孢素和预防性 UDCA 的方案与 PBC 复发和死亡率最低相关。
LAY SUMMARY 为非学术性内容，不纳入译文。
