Fish Eleanor N, Harrison Stephen A, Hassanein Tarek
Eleanor N. Fish, PhD Division of Cellular & Molecular Biology Toronto General Research Institute.
Gastroenterol Hepatol (N Y). 2008 Sep;4(9 18):1-12.
The current standard-of-care for chronic hepatitis C viral infection is treatment with pegylated interferon (PegIFN) plus ribavirin for 24 to 48 weeks. Approximately 50% of HCV-infected patients achieve a sustained viral response (SVR) to this treatment. However, the remaining patients either respond during treatment but relapse upon treatment cessation, respond minimally, or do not respond at all. Much research effort has been expended in attempting to predict those patients who will achieve viral eradication with PegIFN/ribavirin treatment, and it is now clear that those who have either a rapid virologic response (RVR) by week 4 of treatment or a complete early virologic response (cEVR, HCV RNA qualitative negative) by week 12 will go on to achieve SVR at very high rates (70%-90%). Several trials have been completed in patients that fail to achieve RVR or cEVR. These trials include strategies of extending duration of therapy, induction regimens, or retreatment with similar and dissimilar alfa interferons. A recent study of 696 genotype 1 patients treated with both PegIFN and weight-based ribavirin revealed that only 1.6% (4/246) of patients without RVR or cEVR achieved SVR. Consensus interferon, a wholly synthetic interferonalfa, is one of the agents that has been utilized in patients that fail treatment with PegIFN/ribavirin. This molecule has been demonstrated to have a very high affinity for the interferon-alfa receptor, and laboratory studies have demonstrated that it has high levels of antiviral activity. In order to optimally utilize consensus interferon, it is important to understand its unique mechanism of action. In addition, the latest research showing the importance of achieving RVR or cEVR should be reviewed, along with strategies for utilizing consensus interferon in re-treatment, or more specifically upon identification of on-treatment failure in historically difficult-to-treat patients.
慢性丙型肝炎病毒感染目前的标准治疗方案是聚乙二醇化干扰素(PegIFN)联合利巴韦林治疗24至48周。大约50%的丙型肝炎病毒感染患者对该治疗可获得持续病毒学应答(SVR)。然而,其余患者要么在治疗期间有反应但停药后复发,要么反应极小,要么根本无反应。为预测哪些患者使用PegIFN/利巴韦林治疗能实现病毒根除,已投入了大量研究精力,现在很清楚,治疗第4周时具有快速病毒学应答(RVR)或第12周时具有完全早期病毒学应答(cEVR,丙型肝炎病毒RNA定性阴性)的患者将以非常高的比例(70%-90%)实现SVR。针对未实现RVR或cEVR的患者已完成了多项试验。这些试验包括延长治疗疗程、诱导方案或使用相似及不同的α干扰素进行再治疗等策略。最近一项对696例接受PegIFN和基于体重的利巴韦林治疗的基因1型患者的研究显示,没有RVR或cEVR的患者中只有1.6%(4/246)实现了SVR。共识干扰素是一种全合成的α干扰素,是已用于PegIFN/利巴韦林治疗失败患者的药物之一。该分子已被证明对α干扰素受体具有非常高的亲和力,实验室研究表明它具有高水平的抗病毒活性。为了最佳地使用共识干扰素,了解其独特的作用机制很重要。此外,应回顾显示实现RVR或cEVR重要性的最新研究,以及在再治疗中使用共识干扰素的策略,或更具体地说,在识别出既往难以治疗的患者治疗失败时使用共识干扰素的策略。