Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Gastroenterology. 2019 Jan;156(1):96-107.e1. doi: 10.1053/j.gastro.2018.10.001. Epub 2018 Oct 6.
BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group).
We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years).
PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02).
Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.
原发性胆汁性胆管炎（PBC）在肝移植后常复发。我们评估了与 PBC 复发相关的危险因素及其对患者和移植物生存的影响，该研究纳入了来自北美和欧洲 13 个中心的多中心国际队列（全球 PBC 研究组）中的 785 例 PBC 患者（89%为女性）。这些患者在肝移植时的年龄为 54±9 岁，肝移植时间为 1983 年 2 月至 2016 年 6 月。我们分析了肝移植后 12 个月内进行的生化检查结果，以确定胆酶学标志物是否可以识别出 PBC 复发的患者（基于组织学分析）。患者的中位随访时间为 6.9 年（四分位距，6.1-7.9 年）。
5 年后，22%的患者发生 PBC 复发，10 年后，36%的患者发生 PBC 复发。诊断时年龄<50 岁（风险比[HR]，1.79；95%置信区间[CI]，1.36-2.36；P<0.001）、肝移植时年龄<60 岁（HR，1.39；95%CI，1.02-1.90；P=0.04）、使用他克莫司（HR，2.31；95%CI，1.72-3.10；P<0.001）和肝移植后 6 个月时的严重胆汁淤积的生化标志物（胆红素≥100μmol/L 或碱性磷酸酶>正常值上限的 3 倍）（HR，1.79；95%CI，1.16-2.76；P=0.008）与 PBC 复发风险增加相关，而环孢素的使用降低了 PBC 复发的风险（HR，0.62；95%CI，0.46-0.82；P=0.001）。在多变量 Cox 回归中，随着时间的推移，PBC 的复发与移植物丢失（HR，2.01；95%CI，1.16-3.51；P=0.01）和死亡（HR，1.72；95%CI，1.11-2.65；P=0.02）显著相关。
PBC 诊断时或肝移植时年龄较小、使用他克莫司和肝移植后胆酶学标志物升高与 PBC 复发相关。PBC 复发降低了移植物和患者生存的几率。需要采取策略来预防 PBC 复发或降低其负面影响。
