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肝移植后丙型肝炎病毒感染再治疗的疗效:积极治疗方法的作用。

Efficacy of the retreatment of hepatitis C virus infections after liver transplantation: role of an aggressive approach.

机构信息

Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain.

出版信息

Liver Transpl. 2013 Jan;19(1):69-77. doi: 10.1002/lt.23555.

Abstract

A sustained virological response (SVR) is achieved by 30% of naive liver transplantation (LT) recipients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Almost no data are available about retreatment. The aim of this study was to assess the efficacy, tolerability, and SVR predictors of retreatment. Data were collected from 4 centers on the retreatment of prior nonresponders to standard therapy or PEG-IFN (with or without RBV) and relapsers. Seventy-nine of 301 treatment-experienced LT patients (26%), who had a median age of 59 years (range = 35-77 years) and were mostly male (72%) and infected with genotype 1 (87%), were retreated with PEG-IFN and RBV at a median of 6.9 years after LT. During the first course of therapy, 35% were treated with interferon, 49% received tacrolimus, 52% received steroids, and 49.5% were relapsers. Retreatment was started at a median of 1.9 years (range = 45 days to 8.2 years) after the end of the first course. The proportion of patients with cirrhosis increased from 10% to 37% (P < 0.001). In addition, in retreated patients, full initial RBV doses (P = 0.03), growth factors [erythropoietin (P < 0.001) and granulocyte colony-stimulating factor (P = 0.048)], and transfusions (P = 0.03) were used more frequently, and the treatment duration was longer (P = 0.03). An end-of-treatment response was achieved in 61%, whereas SVR, which was associated with improved survival, occurred in 28 (35%). The variables predicting SVR were age (P = 0.04), disease severity [fibrosis (50% with F0-F2 versus 26% with F3-4), P = 0.03; bilirubin, P = 0.006; platelet count, P = 0.03], adherence, and viral kinetics. None of the patients without an early virological response achieved SVR. There was a trend of prior relapsers achieving higher SVR rates than prior nonresponders. In conclusion, SVR, which was achieved by approximately one-third of the retreated patients, can be predicted with the same variables used for naive LT recipients (age, disease severity, adherence, and viral kinetics) and is associated with enhanced survival.

摘要

在接受聚乙二醇干扰素(PEG-IFN)和利巴韦林(RBV)治疗的初治肝移植(LT)受者中,有 30%实现了持续病毒学应答(SVR)。几乎没有关于再治疗的数据。本研究旨在评估再治疗的疗效、耐受性和 SVR 预测因素。该研究的数据来自 4 个中心,包括先前对标准治疗或 PEG-IFN(有或无 RBV)无应答或复发的患者的再治疗。在 301 例治疗经验丰富的 LT 患者中,有 79 例(26%)接受了 PEG-IFN 和 RBV 的再治疗,他们的中位年龄为 59 岁(范围=35-77 岁),主要为男性(72%),感染基因型 1(87%)。这些患者在 LT 后中位时间 6.9 年接受再治疗。在首次治疗过程中,35%的患者接受了干扰素治疗,49%的患者接受了他克莫司治疗,52%的患者接受了类固醇治疗,49.5%的患者为复发。再治疗开始于首次治疗结束后中位时间 1.9 年(范围=45 天至 8.2 年)。肝硬化的比例从 10%增加到 37%(P<0.001)。此外,在再治疗患者中,更频繁地使用了全剂量初始 RBV(P=0.03)、生长因子[促红细胞生成素(P<0.001)和粒细胞集落刺激因子(P=0.048)]和输血(P=0.03),治疗时间也更长(P=0.03)。61%的患者达到了治疗结束时的应答,而 SVR(与生存改善相关)的发生率为 28 例(35%)。预测 SVR 的变量包括年龄(P=0.04)、疾病严重程度[纤维化(50%为 F0-F2 与 26%为 F3-4),P=0.03;胆红素,P=0.006;血小板计数,P=0.03]、依从性和病毒动力学。没有早期病毒学应答的患者均未达到 SVR。与先前无应答者相比,先前复发者达到 SVR 率有升高趋势。总之,大约三分之一的再治疗患者实现了 SVR,这可以通过与初治 LT 受者相同的变量(年龄、疾病严重程度、依从性和病毒动力学)来预测,并且与生存改善相关。

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