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一项为期15年的回顾性研究:丙型肝炎病毒感染的肝移植受者改用西罗莫司后的生存优势。

A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.

作者信息

Shah M, Shankar A, Gee I, Nash K, Hoare M, Gibbs P, Davies S, Alexander G J M

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge University Hospitals, Cambridge, UK.

出版信息

Aliment Pharmacol Ther. 2015 Feb;41(4):379-92. doi: 10.1111/apt.13049. Epub 2014 Dec 11.

Abstract

BACKGROUND

The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus.

AIM

To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis.

METHODS

A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%).

RESULTS

Patients switched to sirolimus had improved survival (P < 0.001) and slower progression to cirrhosis (P = 0.001). In patients with HCC (n = 91), sirolimus duration rather than strategy was an independent predictor of survival (P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03).

CONCLUSION

These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome.

摘要

背景

在肝移植中,尤其是在丙型肝炎病毒(HCV)感染的受者中,使用西罗莫司进行免疫抑制仍存在争议。有证据表明,西罗莫司可延缓肝纤维化,具有肾脏保护作用,可能有助于预防肝细胞癌(HCC)复发。由于对肝动脉血栓形成、移植物丢失及使用西罗莫司初治时死亡风险增加的持续担忧,许多移植中心尚未采用西罗莫司。

目的

回顾转为西罗莫司单一疗法对HCV感染的肝移植受者的生存、移植物丢失及肝纤维化的影响。

方法

对一个中心15年间接受首次HCV肝移植的190例患者进行回顾性研究。113例患者在移植后中位数15个月时,因HCV相关纤维化(72%)、肾功能损害(14%)或高危HCC(5%),从基于钙调神经磷酸酶抑制剂(CNI)的治疗转为低剂量西罗莫司单一疗法。

结果

转为西罗莫司治疗的患者生存率提高(P<0.001),进展为肝硬化的速度减慢(P = 0.001)。在HCC患者(n = 91)中,西罗莫司治疗时间而非治疗策略是生存(P = 0.001)及HCC复发时间延长(33个月对16个月)的独立预测因素。因肾功能不全而转换治疗的患者血清肌酐有所改善(140 - 108μmol/L,P = 0.001)。继续接受CNI治疗的患者更易发生移植后糖尿病(P = 0.03)。

结论

这些数据表明,HCV阳性肝移植受者选择性地转为低剂量西罗莫司单一疗法可改善临床结局。

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