Muir A J, Sylvestre P B, Rockey D C
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Viral Hepat. 2006 May;13(5):322-8. doi: 10.1111/j.1365-2893.2005.00689.x.
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 mug 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.
鉴于丙型肝炎的并发症是由纤维化引起的，我们推测干扰素γ对星状细胞的抗纤维化作用会给丙型肝炎患者带来有益影响。因此，我们评估了干扰素γ-1b对丙型肝炎患者的安全性和疗效。一组20例慢性丙型肝炎患者，他们对先前基于α干扰素的治疗方案无效或不耐受，接受每周三次皮下注射200μg干扰素γ-1b，共24周。在治疗前和治疗结束时进行肝活检。活检由一位单盲病理学家使用经Ishak修改的Knodell系统进行评估，纤维化程度也通过形态计量分析进行量化。研究人群中75%为男性，70%为白种人。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两倍而停止治疗。未发生严重不良事件。形态计量分析显示，6例患者（30%）纤维化评分绝对降低>1%。20例患者中有4例（20%）治疗后Ishak纤维化评分有所改善。总之，干扰素γ治疗对慢性丙型肝炎患者是安全且耐受性良好的。虽然我们未检测到纤维化总体减轻，但干扰素γ-1b治疗使部分患者的纤维化有所减轻。这些数据为进一步研究干扰素γ-1b治疗慢性纤维化肝病患者提供了依据。
