Fabrizi F, Dulai G, Dixit V, Bunnapradist S, Martin P
Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Aliment Pharmacol Ther. 2003 Dec;18(11-12):1071-81. doi: 10.1046/j.1365-2036.2003.01780.x.
The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.
We evaluated the efficacy and safety of initial interferon monotherapy in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses.
We have identified 14 clinical trials (269 unique patients); two were controlled studies. The mean overall estimate for sustained virological response (SVR) and drop-out rate was 37%[95% confidence interval (CI) 28-48] and 17% (95% CI 10-28), respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms (17%), neurological (21%) and gastrointestinal (18%). The overall weighted estimate for SVR in patients with hepatitis C virus genotype 1 was 30.6% (95% CI 20.9-48). In the sub-group of clinical trials (n = 5) with standard interferon administration (3 million units [MUI] thrice weekly, subcutaneous route, 24-week treatment), the overall mean estimate of SVR was 39% (95% CI 25-56). The studies were heterogeneous with regard to SVR and drop-out rate.
Tolerance to initial interferon monotherapy was lower in dialysis than nonuremic patients with chronic hepatitis C. However, more than one-third of haemodialysis patients with chronic hepatitis C have been successfully treated with interferon. Longer duration of interferon monotherapy does not appear to have a beneficial effect on the response rate. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in dialysis population.
尽管已经发表了一些针对此问题的小型临床试验,但干扰素单药治疗对慢性丙型肝炎透析患者的疗效仍不明确。
我们通过对文献进行系统综述并对临床试验进行荟萃分析,评估了慢性丙型肝炎透析患者初始干扰素单药治疗的疗效和安全性。主要结局为持续病毒学应答(作为疗效指标);次要结局为脱落率(作为耐受性指标)。我们采用Der Simonian和Laird的随机效应模型,并进行了异质性和敏感性分析。
我们纳入了14项临床试验(269例独立患者);其中两项为对照研究。持续病毒学应答(SVR)和脱落率的总体平均估计值分别为37%[95%置信区间(CI)28 - 48]和17%(95% CI 10 - 28)。需要中断治疗的最常见副作用为流感样症状(17%)、神经症状(21%)和胃肠道症状(18%)。丙型肝炎病毒基因1型患者SVR的总体加权估计值为30.6%(95% CI 20.9 - 48)。在采用标准干扰素给药(300万单位[MUI],每周三次,皮下注射,24周治疗)的临床试验亚组(n = 5)中,SVR的总体平均估计值为39%(95% CI 25 - 56)。这些研究在SVR和脱落率方面存在异质性。
与慢性丙型肝炎的非尿毒症患者相比,透析患者对初始干扰素单药治疗的耐受性较低。然而,超过三分之一的慢性丙型肝炎血液透析患者已通过干扰素成功治疗。干扰素单药治疗疗程延长似乎对缓解率没有有益影响。有必要进一步开展研究以确定透析人群中慢性丙型肝炎的最佳抗病毒治疗方案。