Interferon-gamma To Treat Chronic HCV Infection

描述（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， 不满意。用干扰素-α和利巴韦林治疗会导致 在少数患者中持续反应，许多患者可能不会 由于与这些药物相关的副作用而有资格接受治疗。 其他治疗选择显然是必要的慢性丙型肝炎 感染慢性丙型肝炎感染的主要并发症是 纤维化，最终导致肝硬化的发展。动物模型 已经证明干扰素-γ通过其作用减少纤维化 在星状细胞上。特发性肺动脉高压的近期报告 发现干扰素-γ耐受性良好， 肺功能，表面上是由于减少纤维化。鉴于这些 数据，我们假设，不仅干扰素-γ将有效 治疗丙型肝炎介导的纤维化，而且它将是安全的。 因此，我们建议进行第一阶段研究，以评估 20例慢性丙型肝炎患者干扰素-γ治疗观察的 患者将包括既往治疗失败的患者， 干扰素-α或不是干扰素-α治疗的候选者。男性或 年满18岁的妇女有资格参加。其他入选标准为血清 PCR检测丙型肝炎病毒阳性;肝活检符合慢性 肝炎，并且在Knodell量表上纤维化评分至少为1; 代偿性肝病;以及在 入境所有患者将接受三次200微克的干扰素-γ 一周十二个月。患者将在治疗前接受肝活检 在治疗结束时。将在第1周评价安全性和耐受性， 治疗期间第2、4、8周，然后每4周一次，以及治疗后第4和12周 完成治疗。在开始前评价血清HCV-RNA 在治疗和治疗结束时。 本研究的主要终点将是组织学反应， 慢性丙型肝炎感染患者接受干扰素-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.