CLINICAL TRIAL: THE HEPATITIS C ANTIVIRAL LONG-TERM TREATMENT AGAINST CIRRHOSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是确定基于干扰素的长期治疗是否可以在合理数量的受试者中实现并在几年内保持不变，以及预期的好处是否值得承担相关的风险和费用。研究人群将限于那些进展为肝硬变或其并发症风险最高的人，即在研究开始时确诊为纤维化或肝硬变的患者。由于所有登记的患者以前都接受过不同的治疗，目前的研究设计规定，所有进入长期研究部分的患者都是从共同的起点开始的，并有第二次机会达到持续的病毒学反应。在最初的治疗过程中，所有患者将接受为期24周的聚乙二醇干扰素和利巴韦林治疗，并在20周进行病毒学评估，以驳斥他们的无应答状态。因此，进入长期研究的患者将知道，他们已经接受了最新的方案，试图实现病毒学清除，并且在失败后，现在可以确定他们对传统疗法没有反应。预计大约20%的人在20周时血清中没有检测到病毒，这组人可能会继续治疗，并接受为期48周的全程治疗。那些在20周后血清中仍为丙型肝炎病毒阳性的患者将被随机分为两组，要么继续接受聚乙二醇干扰素(不再使用利巴韦林)，要么在接下来的3年和1年半内不再接受进一步治疗，除非仔细观察。第20周在36、48、60或72周出现可检测到的丙型肝炎病毒核糖核酸的应答者可以随机接受持续的聚乙二醇干扰素(不再使用利巴韦林)，或者除了仔细观察之外不再接受进一步的治疗，再观察42个月。 治疗终点将有两种类型：疾病的组织学进展以及肝硬变失代偿证据的发展。将获得干扰素副作用的程度以及对所有研究参与者的生活质量的详细评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of the present study is to determine whether prolonged interferon-based therapy can be achieved and maintained in a reasonable number of subjects over several years' time, and whether the anticipated benefits are worth the risk and expense involved. The study population will be limited to those at highest risk of progression to cirrhosis or its complications, namely, patients with established fibrosis or cirrhosis on biopsy at study entry. Since all patients enrolled will have had different previous treatments, the present study design provides that all patients entering the long-term portion of the study have begun at a common starting point and have had a second chance at reaching a sustained virologic response. In the initial course of therapy all patients will be treated with peginterferon plus ribavirin for a period of 24 weeks, with virologic assessment at 20 weeks to refute their nonresponder status. Thus, patients entering the long-term study will know that they have been given the very latest regimen in an attempt to achieve virologic clearance and, having failed, now can be certain that they are non-responders to conventional therapy. It is anticipated that approximately 20% will have no detectable virus in serum at the 20 week point, and that this group may continue treatment and receive a full course of 48 weeks' therapy. Those who remain HCV-positive in serum at 20 weeks will be randomized to receive either continued peginterferon (without further ribavirin) or no further treatment beyond careful observation for the ensuing 3 and 1/2 years. Week 20 responders who develop detectable HCV RNA at weeks 36, 48, 60 or 72 may be randomized to receive either continued peginterferon (without further ribavirin) or no further treatment beyond careful observation for an additional 42 months. Therapeutic endpoints will be of two types: histologic progression of disease as well as development of evidence of cirrhotic decompensation. The extent of side effects of interferon as well as a detailed assessment of quality of life will be obtained for all study participants.