Interferon gamma-1b for the treatment of fibrosis in chronic hepatitis C infection
Interferon gamma-1b for the treatment of fibrosis in chronic hepatitis C infection
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DOI：
10.1111/j.1365-2893.2005.00689.x
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发表时间：
2006-05-01
影响因子：
2.5
通讯作者：
Rockey, DC
中科院分区：
文献类型：
--
作者：
Muir, AJ;Sylvestre, PB;Rockey, DC
鉴于丙型肝炎的并发症是由于纤维化，我们假设干扰素γ对星状细胞的抗纤维化作用将导致丙型肝炎患者的有益效果。因此，我们评估了干扰素γ-1b在丙型肝炎患者中的安全性和有效性。一组20例慢性丙型肝炎患者，他们对以前的以α-干扰素为基础的方案失败或不耐受，接受200 μ g干扰素γ-1b皮下注射，每周三次，持续24周。在治疗前和治疗结束时进行肝活检。由单盲病理学家使用Ishak改良的Knodell系统评价活检，并通过形态测定分析定量纤维化。研究人群中75%为男性，70%为白人。平均年龄为47.9 ± 7.5岁。20例患者中有18例完成了治疗。1例患者因全身症状停止治疗。1例患者因转氨酶升高超过基线的两倍而停止治疗。未发生严重不良事件。形态测定分析显示，6名患者（30%）的纤维化评分绝对降低> 1%。20例患者中有4例（20%）治疗后Ishak纤维化评分改善。总之，干扰素γ治疗慢性丙型肝炎患者安全且耐受性良好。虽然我们没有检测到纤维化的总体减少，但干扰素γ-1b治疗导致选定患者的纤维化减少。这些数据为进一步研究干扰素γ-1b在慢性纤维化肝病患者中的作用提供了基础。
Given that the complications of hepatitis C are due to fibrosis, we hypothesized that the antifibrotic effects of interferon gamma on stellate cells would lead to beneficial effects in patients with hepatitis C. Thus, we evaluated the safety and efficacy of interferon gamma-1b in patients with hepatitis C. A cohort of 20 patients with chronic hepatitis C who failed or were intolerant to previous interferon-alpha-based regimens received 200 mu g of interferon gamma-1b subcutaneously three times weekly for 24 weeks. Liver biopsy was performed prior to and at the end of treatment. Biopsies were evaluated by a single blinded pathologist using the Knodell system modified by Ishak, and fibrosis was also quantitated by morphometric analysis. The study population was 75% male and 70% Caucasian. Mean age was 47.9 +/- 7.5 years. Eighteen of 20 patients completed therapy. One patient discontinued therapy because of constitutional symptoms. One patient discontinued therapy because of elevated aminotransferases greater than twice baseline. No serious adverse events occurred. Morphometric analysis revealed that six patients (30%) had > 1% absolute reduction in fibrosis score. Four of 20 (20%) patients had improvement in Ishak fibrosis scores after treatment. In conclusion, interferon gamma therapy is safe and well tolerated in patients with chronic hepatitis C. Although we did not detect an overall reduction in fibrosis, interferon gamma-1b treatment led to a reduction in fibrosis in selected patients. These data provide a basis for further study of interferon gamma-1b in patients with chronic fibrosing liver disease.