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肝移植受者的丙型肝炎病毒治疗:反应预测指标、对纤维化进展的影响以及纤维化初始阶段的重要性

Hepatitis C virus therapy in liver transplant recipients: response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis.

作者信息

Roche Bruno, Sebagh Mylene, Canfora Maria Laura, Antonini Teresa, Roque-Afonso Anne-Marie, Delvart Valerie, Saliba Faouzi, Duclos-Vallee Jean-Charles, Castaing Denis, Samuel Didier

机构信息

AP-HP Hopital Paul Brousse, Centre Hepato-Biliaire, Villejuif, France.

出版信息

Liver Transpl. 2008 Dec;14(12):1766-77. doi: 10.1002/lt.21635.

Abstract

Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome. A total of 113 hepatitis C virus (HCV)-infected LT patients received 133 courses of IFN (standard, n = 29, pegylated IFN [pegIFN], n = 104) and RBV (75% genotype 1). Early virological response (EVR), end-of-treatment (EOT), and SVR were obtained in 74%, 55%, and 38%, respectively. EVR, completion of treatment, viral load before therapy, genotype non-1, and use of pegIFN were predictive of SVR, but only EVR remained in the multivariate analysis. SVR was obtained in 45% patients who received a second course of therapy. Paired biopsies at baseline, at EOT and at long-term were available in 42 patients. The mean fibrosis stage remained stable in patients with SVR and increased in patients without response. Rejection episodes were observed in 6% of patients. Tolerability of therapy decrease in patients with fibrosis stage > or =3 on baseline liver biopsy. A total of 20% of them died or were retransplanted due to liver failure as opposed to 1% of patients who had fibrosis stage <3. In conclusion, IFN and RBV achieved SVR in 38% of patients. EVR is independently associated with SVR. Fibrosis stage remained stable in patients with SVR and increased in nonresponders. Fibrosis stage > or =3 was associated with a high rate of liver failure, arguing for an early introduction of antiviral therapy.

摘要

肝移植(LT)后使用干扰素(IFN)和利巴韦林(RBV)进行抗病毒治疗可使持续病毒学应答(SVR)率达到20%至45%。我们研究的目的是评估治疗的疗效和耐受性、对纤维化进展的影响以及初始纤维化阶段对预后的重要性。共有113例丙型肝炎病毒(HCV)感染的LT患者接受了133个疗程的IFN(标准IFN,n = 29;聚乙二醇化干扰素[pegIFN],n = 104)和RBV(75%为1型基因型)治疗。早期病毒学应答(EVR)、治疗结束时(EOT)和SVR的获得率分别为74%、55%和38%。EVR、治疗完成情况、治疗前病毒载量、非1型基因型以及使用pegIFN可预测SVR,但在多变量分析中只有EVR仍然具有预测价值。接受第二个疗程治疗的患者中有45%获得了SVR。42例患者在基线、EOT和长期时有配对活检样本。SVR患者的平均纤维化阶段保持稳定,无应答患者的纤维化阶段则有所增加。6%的患者出现了排斥反应。基线肝活检纤维化阶段≥3的患者治疗耐受性下降。其中共有20%的患者因肝衰竭死亡或接受再次移植,而纤维化阶段<3的患者这一比例为1%。总之,IFN和RBV使38%的患者获得了SVR。EVR与SVR独立相关。SVR患者的纤维化阶段保持稳定,无应答者则增加。纤维化阶段≥3与肝衰竭的高发生率相关,这表明应尽早引入抗病毒治疗。

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