Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis
Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis
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DOI：
10.1002/hep.21561
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发表时间：
2007-03-01
期刊：
影响因子：
13.5
通讯作者：
Faris-Young, Sima
中科院分区：
文献类型：
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作者：
Pockros, Paul J.;Jeffers, Lennox;Faris-Young, Sima
干扰素-γ1b是一种多效性细胞因子，具有抗纤维化、抗病毒和抗增殖活性。在一项双盲安慰剂对照研究中，共有502名代偿性肝病患者和Ishak纤维化评分为4-6的患者被随机选择，其中488名患者接受了为期48周的每周3次皮下注射干扰素-γ1b 100毫克(组1，n=169)、干扰素-γ1b 200毫克(组2，n=157)或安慰剂(组3，n=162)。大多数患者(83.6%)在基线时有肝硬变(Ishak评分为5或6)。治疗后的肝活检以盲法评估是否减少1个或更多的Ishak点(主要终点)。420名接受治疗前和治疗后肝活检的患者是可评估的，3个治疗组之间的Ishak评分没有改善(组1、2和3的患者分别为12.1%、12.4%和16%；P>；0.05)。干扰素诱导的生物标志物分析显示，干扰素诱导的T细胞-α趋化因子(ITAC)是一种干扰素诱导的CXCR3趋化因子，是Ishak评分稳定或改善的独立预测因子。干扰素-γ1b耐受性良好。所有3个手臂(分别为5个、5个和4个)的死亡人数相似，且大多数与肝硬变并发症有关。结论：干扰素-γ1b治疗1年内不能逆转晚期肝病患者的肝纤维化。ITAC水平升高的患者亚组以及可能不太严重的疾病可能被考虑用于未来的干扰素-伽马1b研究。
Interferon-gamma 1b (IFN-gamma 1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-gamma 1b 100 mu g (group 1, n = 169), IFN-gamma 1b 200 mu g (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P > 0.05). Analysis of IFN-gamma-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-gamma-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-gamma 1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. Conclusion: IFN-gamma 1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-gamma 1b.