Interferon-gamma To Treat Chronic HCV Infection

说明(改编自应用程序) 目前慢性丙型肝炎感染的治疗选择仍然有限， 不能令人满意。使用干扰素-α和利巴韦林治疗导致 少数患者持续有效，而许多患者可能没有 由于与这些药物相关的副作用，有资格接受治疗。 慢性丙型肝炎显然需要其他治疗方案 感染。慢性丙型肝炎感染的一个主要并发症是 肝纤维化，最终导致发展为肝硬变。动物模型 已经证明，干扰素-γ通过其作用减少纤维化的形成 在星状细胞上。特发性肺病近期一例报告 纤维化研究发现，干扰素-γ耐受性良好，并导致改善 肺功能，表面上是由于纤维化的减少。考虑到这些 数据，我们假设不仅干扰素-伽马将对 治疗丙型肝炎介导的肝纤维化，也是安全的。 因此，我们建议进行第一阶段研究，以评估 干扰素-γ治疗慢性丙型肝炎20例这个 患者将包括那些以前的治疗失败的人 干扰素-α或不适用于干扰素-α治疗。男性或 年满18周岁或以上的女性有资格。其他入选标准包括血清 聚合酶链式反应检测丙型肝炎病毒阳性；肝活检符合慢性 肝炎，肝纤维化评分在克诺德分级中至少1分； 补偿性肝病；以及在此之前获得知情的书面同意 进入。所有患者将接受三次200微克的干扰素-伽马 十二个月的一周。患者在治疗前将接受肝脏活检。 在治疗结束时。安全性和耐受性将在第1周进行评估， 2、4、8，然后每4周治疗一次，并在治疗后的4周和12周 完成治疗。血清丙型肝炎病毒核糖核酸将在启动前进行评估 治疗和治疗结束时。 这项研究的主要终点将是组织学反应 慢性丙型肝炎患者需接受干扰素-γ治疗。 次要终点包括生化反应、炎症和 调节细胞因子水平和治疗期间的生活质量。

DESCRIPTION (adapted from the application) Current treatment options for chronic hepatitis C infection remain limited and unsatisfactory. Treatment with interferon-alpha and ribavirin leads to a sustained response in the minority of patients, and many patients may not be eligible for treatment due to side effects associated with these medications. Other treatment options are clearly necessary for chronic hepatitis C infection. A major complication of chronic hepatitis C infection is fibrogenesis, ultimately leading to development of cirrhosis. Animal models have demonstrated that interferon-gamma reduces fibrogenesis through its effect on stellate cells. A recent report in patients with idiopathic pulmonary fibrosis found that interferon-gamma was well-tolerated and led to improved pulmonary function, ostensibly due to a reduction in fibrogenesis. Given these data, we postulate not only that interferon-gamma will be effective for treatment of hepatitis C mediated fibrogenesis, but also that it will be safe. We have therefore proposed a phase I study to assess the effectiveness of interferon-gamma in twenty patients with chronic hepatitis C infection. The patients will include those who have failed previous therapy with interferon-alpha or are not candidates for interferon-alpha therapy. Men or women 18 years of age or older are eligible. Other inclusion criteria are serum positive for hepatitis C virus by PCR; liver biopsy consistent with chronic hepatitis and with a fibrosis score of at least one on the Knodell scale; compensated liver disease; and informed, written consent obtained prior to entry. All patients will receive 200 micrograms of interferon-gamma three times a week for twelve months. Patients will undergo liver biopsy prior to treatment and at the end of treatment. Safety and tolerance will be evaluated at weeks 1, 2, 4, 8 and then every 4 weeks during treatment and at weeks 4 and 12 following the completion of therapy. Serum HCV-RNA will be evaluated prior to initiating therapy and at the end of therapy. The primary endpoint of this study will be the histological response of patients with chronic hepatitis C infection to treatment with interferon-gamma. Secondary endpoints include the biochemical response, inflammatory and regulatory cytokine levels, and quality of life during treatment.