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肝移植后丙型肝炎复发:对全剂量聚乙二醇干扰素和利巴韦林的病毒学及组织学反应

Hepatitis C recurrence after liver transplantation: Viral and histologic response to full-dose PEG-interferon and ribavirin.

作者信息

Oton E, Barcena R, Moreno-Planas J M, Cuervas-Mons V, Moreno-Zamora A, Barrios C, Garcia-Garzon S, Moreno A, Boullosa-Graña E, Rubio-Gonzalez E E, Garcia-Gonzalez M, Blesa C, Mateos M L

机构信息

Liver-gastroenterology Department, Ramon y Cajal Hospital, Madrid.

出版信息

Am J Transplant. 2006 Oct;6(10):2348-55. doi: 10.1111/j.1600-6143.2006.01470.x. Epub 2006 Jul 26.

Abstract

Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.

摘要

肝移植(LT)后丙型肝炎复发很常见,且常导致肝硬化和死亡。我们研究的目的是评估在一个多中心队列中,55例肝移植后≥12个月的患者使用48周全剂量聚乙二醇化干扰素-α-2a(n = 4)或α-2b(n = 51)加利巴韦林(>11 mg/kg/天)的疗效和安全性。所有受试者经组织学证实为丙型肝炎病毒复发,不包括严重胆汁淤积性复发。平均年龄为54.3±9.7岁,男性占77%,90.9%为1型基因型,32.7%为肝硬化患者。除5例患者外,所有患者均接受他克莫司(54.5%)、环孢素(30.7%)或霉酚酸酯(5.5%)单药治疗。治疗结束时的应答率和持续病毒学应答(SVR)率分别为66.7%和43.6%。低基线丙型肝炎病毒核糖核酸(p = 0.005)以及肝移植至治疗的时间在2至4年之间(p = 0.011)是持续病毒学应答的预测因素。在第4周时病毒载量下降未≥1 log10和/或在第12周时未下降≥2 log10可100%预测治疗失败。最常见的副作用是中性粒细胞减少(76.4%)、贫血(60%)和感染并发症(30.9%)。毒性导致16例(29%)受试者停用聚乙二醇化干扰素。15例接受治疗后活检的患者,组织学活动指数显著改善(p = 0.006),而纤维化未改变(p = 0.14)。3例患者死亡(胆管炎、肝动脉血栓形成和肺癌)。总之,肝移植后丙型肝炎病毒治疗非常有效,尽管会导致较高的毒性发生率。

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