[EASL2013]HCV抗病毒药物副作用——贫血更常见

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Boceprevir和Telaprevir治疗丙型肝炎病毒（HCV）的III期临床试验在治疗应答上提供了重要的信息，虽然数据缺乏特定的人群，尤其是针对那些难治性的病人，如肝硬化。在2013年欧洲肝病学会（European Association for the Study of the Liver,EASL）主办的国际肝病大会（the International Liver Congress,ILC）上，北卡罗莱纳大学M.W. Fried等人开展了一项研究——HCV-TARGET，为了评估目前在美国和加拿大广泛应用的三联疗法的疗效。

        这项正在进行的研究共纳入1068名患者。受试者大多数是男性（60%），白人（76%），40–64岁之间（84%）；非洲裔美国人占20%，7%的患者年龄超过65岁；35%有肝硬化。基因型1A/1B/未分类型分别占61%，22%，11%；49%的是初治患者。76%的患者因不良事件（AE）需要医疗干预或调整抗病毒治疗剂量。56%的患者发生贫血，血红蛋白最低点≤8.5g/dl（12%）或8.5~10g/dl（26%）。处理措施：利巴韦林剂量减少（45%），促红细胞生成素（15%），和/或输血（8%）。29%的患者出现皮疹且1%因皮疹停止治疗。在11例（4%）肝硬化患者中出现新的不可逆事件（腹水，肝性脑病，静脉曲张出血）。5%的无肝硬化患者和10%的肝硬化患者因不良事件提前终止治疗。数据收集正在进行中，SVR数据将提交。

        后续的分析将提醒临床医生关注这些先前受忽视的人群以及对不良事件的处理。

论文摘要：

HCV-TARGET: a longitudinal, observational study of north american patients with chronic hepatitis c (hcv) treated with boceprevir or telaprevir

Phase III trials of boceprevir and telaprevir for HCV provided important information on treatment response, although data is lacking for certain groups, especially those with “difficult to cure” characteristics such as African Americans and cirrhosis. The aim of HCV-TARGET is to evaluate the effects of triple therapy in the broader population now being treated in the United States and Canada, including those underrepresented in clinical trials.

Methods: The HCV-TARGET consortium of academic and community investigators utilizes novel, standardized source data abstraction and a common database to enroll sequential patients treated with regimens that include boceprevir and telaprevir. Demographic, clinical, adverse event, and virological data are collected throughout treatment and post-treatment follow-up. Whole blood for DNA and serum from specified time points are stored at a central biorepository.

Results: In this ongoing study, 1068 participants have been enrolled to date of whom 816, at varying stages of treatment (telaprevir 77%, boceprevir 23%), are included in this preliminary analysis. The majority are male (60%), Caucasian (76%), and between ages 40–64 years (84%). African Americans comprised 20% of participants and 7% of patients were older than 65 years. Cirrhosis, defined by biopsy or clinical criteria, was present in 35%. Genotype 1a/1b/not subtyped was 61%, 22%, 11%, respectively, and 49% were treatment naïve. Adverse events (AE) requiring medical intervention or dose modification to the antiviral regimen occurred in 76%. Anemia, occurring in 56% with nadir hemoglobin ≤8.5 g/dl (12%) or 8.5–10 g/dl (26%), was managed with ribavirin dose reduction (45%),EPO (15%), and/or transfusion (8%). Rash was noted in 29% while
1% discontinued treatment due to rash. A new decompensating event (ascites, encephalopathy, variceal hemorrhage) occurred in 11 (4%) cirrhotic patients. Treatment was prematurely discontinued due to AE in 5% of non-cirrhotic and 10% of cirrhotic patients. Data collection is ongoing and SVR data will be presented.

Conclusions: HCV-TARGET encompasses the North American experience with boceprevir and telaprevir across a broad spectrum of clinical practices in a cohort enriched with African American
patients and cirrhosis. Continuing analyses will inform clinicians regarding these previously underrepresented populations and best practices for managing adverse events.