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基于博赛泼维与特拉泼维的三联疗法治疗慢性丙型肝炎:病毒学疗效及其对肾功能和终末期肝病模型评分的影响

Boceprevir and telaprevir-based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end-stage liver disease score.

作者信息

Virlogeux V, Pradat P, Bailly F, Funingana G, Gonçalves F, Maynard M, Hartig-Lavie K, Amiri M, Zoulim F

机构信息

Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France; Lyon University, Lyon, France; Inserm U1052, Lyon, France; ENS, Lyon, France.

出版信息

J Viral Hepat. 2014;21(9):e98-e107. doi: 10.1111/jvh.12237. Epub 2014 Feb 25.

Abstract

Triple therapy using telaprevir or boceprevir [hepatitis C virus (HCV)-NS3/NS4A protease inhibitors (PI)] in association with PEG-IFN/ribavirin has recently become the new standard of care (SOC) for treatment of HCV genotype 1 patients. Our objective was to assess the efficacy and tolerance of triple therapy in routine clinical practice. A total of 186 consecutive HCV patients initiating triple therapy were enrolled in a single centre study. Clinical, biological and virological data were collected at baseline and during follow-up as well as tolerance and side effect details. Among 186 HCV patients initiating triple therapy, 69% received telaprevir and 31% boceprevir. Sixty-one per cent of patients had cirrhosis. The overall extended rapid virological response (eRVR) rate and sustained virological response (SVR) rate were 57.0% and 59.7%, respectively. IL28B CC phenotype was associated with increased probability of achieving eRVR and SVR, whereas previous non-response was associated with low eRVR and SVR rates. The SVR rate increased from 30.8% in previously non-responders to 59.1% in partial non-responders and 75% in relapsers. SVR rate in naive patients was 62.5%. Glomerular filtration rate assessed by MDRD after 12 weeks of therapy was significantly reduced for both PI (P < 0.001). The model for end-stage liver disease (MELD) score was significantly increased at W12 for telaprevir (P = 0.008) and at W24 for boceprevir (P = 0.027). PI-based triple therapy leads to high rates of virological response even in previously non-responder patients. Renal function after triple therapy is impaired as well as MELD score in all patients. Cautious clinical monitoring should focus not only on haematological and dermatological side effects but also on renal function.

摘要

使用特拉匹韦或博赛匹韦(丙型肝炎病毒(HCV)-NS3/NS4A蛋白酶抑制剂(PI))联合聚乙二醇干扰素/利巴韦林的三联疗法最近已成为治疗HCV基因1型患者的新的标准治疗方案(SOC)。我们的目的是评估三联疗法在常规临床实践中的疗效和耐受性。总共186例开始三联疗法的连续性HCV患者被纳入一项单中心研究。在基线、随访期间收集临床、生物学和病毒学数据以及耐受性和副作用细节。在186例开始三联疗法的HCV患者中,69%接受特拉匹韦,31%接受博赛匹韦。61%的患者有肝硬化。总体延长快速病毒学应答(eRVR)率和持续病毒学应答(SVR)率分别为57.0%和59.7%。IL28B CC基因型与实现eRVR和SVR的概率增加相关,而既往无应答与低eRVR和SVR率相关。SVR率从既往无应答者的30.8%增加到部分无应答者的59.1%和复发者的75%。初治患者的SVR率为62.5%。治疗12周后通过MDRD评估的肾小球滤过率在两种PI治疗组中均显著降低(P<0.001)。终末期肝病模型(MELD)评分在第12周时特拉匹韦组显著升高(P=0.008),在第24周时博赛匹韦组显著升高(P=0.027)。基于PI的三联疗法即使在既往无应答患者中也能产生较高的病毒学应答率。三联疗法后所有患者的肾功能以及MELD评分均受损。谨慎的临床监测不仅应关注血液学和皮肤病学副作用,还应关注肾功能。

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