The Royal Free Sheila Sherlock Liver Centre and Division of Surgery and International Sciences, University College London, London, United Kingdom.
Liver Transpl. 2010 Jan;16(1):64-73. doi: 10.1002/lt.21960.
Patients with primary biliary cirrhosis (PBC), despite excellent outcomes after liver transplantation (LT), may develop recurrent primary biliary cirrhosis (rPBC). The impact of immunosuppression and HLA mismatches on rPBC is unclear. We evaluated 103 consecutive PBC patients who underwent transplantation (follow-up > or = 10 months) with serial protocol biopsies. Cox regression was used to evaluate factors associated with rPBC: the Model for End-Stage Liver Disease score pre-LT, year of transplantation, age and gender of the recipient and donor, cold and warm ischemic times, HLA mismatches, rejection, infections, and immunosuppression (initial/maintenance). The mean follow-up was 108 months (10-239 months), rPBC occurred in 36, and the mean was 44 months (10-200 months). Immunosuppression was cyclosporine-based in 38 (10 initially on monotherapy) and tacrolimus-based in 62 (19 initially on monotherapy). Steroids were discontinued in all but 7. Azathioprine was part of the initial immunosuppression in 70, 26 discontinued it, and 33 were never exposed to it. rPBC was associated independently with nonuse/discontinuation of azathioprine (P = 0.015, hazard ratio = 0.046, 95% confidence interval = 0.008-0.261). The mean time to rPBC was 74 months with azathioprine, 43 months when AZA was discontinued, and 31 months if no azathioprine was used. Cyclosporine or tacrolimus alone had no impact on rPBC, but cyclosporine with azathioprine was protective for rPBC in comparison with tacrolimus/azathioprine (0/18 versus 7/25, respectively; P < 0.001). rPBC was not affected by HLA mismatches. Azathioprine use in PBC patients who underwent transplantation was associated with less disease recurrence and a longer time to rPBC. Tacrolimus or cyclosporine individually had no effect, but cyclosporine and azathioprine in combination resulted in the least rPBC.
原发性胆汁性肝硬化（PBC）患者尽管在肝移植（LT）后预后良好，但仍可能发生复发性原发性胆汁性肝硬化（rPBC）。免疫抑制和 HLA 错配对 rPBC 的影响尚不清楚。我们评估了 103 例连续接受 PBC 移植（随访> = 10 个月）并进行了系列方案活检的患者。使用 Cox 回归评估与 rPBC 相关的因素：LT 前终末期肝病模型评分、移植年份、受体和供体的年龄和性别、冷缺血和热缺血时间、HLA 错配、排斥反应、感染和免疫抑制（初始/维持）。平均随访 108 个月（10-239 个月），36 例发生 rPBC，平均时间为 44 个月（10-200 个月）。免疫抑制采用环孢素基础治疗 38 例（10 例初始单药治疗），采用他克莫司基础治疗 62 例（19 例初始单药治疗）。除 7 例外，其余均停用类固醇。70 例初始免疫抑制方案中使用了硫唑嘌呤，26 例停用，33 例从未使用过。rPBC 与硫唑嘌呤的不使用/停用独立相关（P = 0.015，风险比 = 0.046，95%置信区间 = 0.008-0.261）。使用硫唑嘌呤的 rPBC 平均时间为 74 个月，停用硫唑嘌呤的 rPBC 时间为 43 个月，未使用硫唑嘌呤的 rPBC 时间为 31 个月。环孢素或他克莫司单独使用对 rPBC 无影响，但与他克莫司/硫唑嘌呤相比，环孢素加硫唑嘌呤对 rPBC 具有保护作用（分别为 0/18 与 7/25，P < 0.001）。HLA 错配对 rPBC 无影响。移植后使用硫唑嘌呤的 PBC 患者 rPBC 复发率较低，rPBC 发生时间较长。环孢素或他克莫司单独使用无影响，但环孢素和硫唑嘌呤联合使用 rPBC 发生率最低。
