Desai Tusar K, Jamil Laith H, Balasubramaniam Mamtha, Koff Raymond, Bonkovsky Herbert L
William Beaumont Hospital, Royal Oak, MI, USA.
Dig Dis Sci. 2008 Mar;53(3):815-22. doi: 10.1007/s10620-007-9945-7. Epub 2007 Sep 12.
Prospective randomized controlled trials (RCTs) comparing phlebotomy and interferon (IFN) treatment to IFN alone in patients with chronic hepatitis C (CHC) have suggested a benefit for the phlebotomy group. However, statistical significance was achieved in only one of these trials. We performed a meta-analysis of RCTs comparing phlebotomy and IFN to IFN alone for the treatment of CHC. The MEDLINE database and Cochrane registry of controlled trials were searched using the key words "phlebotomy" and "treatment of hepatitis C." Reference lists of review articles discussing the interaction between iron and CHC, and prospective RCTs comparing phlebotomy plus IFN therapy to IFN alone were searched to identify additional RCTs that compared phlebotomy plus IFN to IFN alone. Peto odds ratios with their 95% confidence intervals and Forrest plots were generated for each variable to assess the relationships among the studies that had provided that information. Statistical analysis was performed using Comprehensive META-Analysis version 2.0. Six prospective RCTs were identified: all used sustained viral response (SVR) as an endpoint. The three largest RCTs excluded patients with cirrhosis. Two RCTs specifically included only patients with either high ferritin or high hepatic iron content. IFN treatment regimes varied. Length of treatment varied between 6 and 12 months. The phlebotomy plus IFN group and the IFN group did not differ with respect to the percentage of patients with cirrhosis or genotype 1. SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN group, compared to 22/185 (12%) patients in the IFN group. Peto odds ratio for SVR in phlebotomy plus IFN group was 2.7; 95% CI 1.6-4.5, P < 0.0001. All five RCTs published in manuscript form showed a trend towards a benefit from the phlebotomy plus IFN in attaining SVR, and the results of the meta-analysis were not dependent on any single RCT, since excluding any single RCT did not change the results. Phlebotomy improves the SVR in response to IFN treatment in patients with CHC. Confirmation of this will require RCT with detailed pre-treatment iron studies and appropriately powered to demonstrate a statistically significant benefit.
在慢性丙型肝炎（CHC）患者中，比较放血疗法联合干扰素（IFN）治疗与单用IFN治疗的前瞻性随机对照试验（RCT）表明放血疗法组有获益。然而，这些试验中只有一项取得了统计学显著性。我们对比较放血疗法联合IFN与单用IFN治疗CHC的RCT进行了荟萃分析。使用关键词“放血疗法”和“丙型肝炎治疗”检索MEDLINE数据库和Cochrane对照试验注册库。检索了讨论铁与CHC相互作用的综述文章的参考文献列表，以及比较放血疗法联合IFN治疗与单用IFN治疗的前瞻性RCT，以识别其他比较放血疗法联合IFN与单用IFN治疗的RCT。为每个变量生成Peto比值比及其95%置信区间和福里斯特图，以评估提供该信息的研究之间的关系。使用Comprehensive META-Analysis 2.0版进行统计分析。共识别出六项前瞻性RCT：均将持续病毒学应答（SVR）作为终点。三项最大的RCT排除了肝硬化患者。两项RCT专门仅纳入了铁蛋白高或肝铁含量高的患者。IFN治疗方案各不相同。治疗时长在6至12个月之间。放血疗法联合IFN组和IFN组在肝硬化患者或1型基因型患者的百分比方面无差异。放血疗法联合IFN组182例患者中有50例（27%）实现了SVR，而IFN组185例患者中有22例（12%）实现了SVR。放血疗法联合IFN组SVR的Peto比值比为2.7；95%置信区间为1.6 - 4.5，P < 0.0001。以手稿形式发表的所有五项RCT均显示放血疗法联合IFN在实现SVR方面有获益趋势，荟萃分析的结果不依赖于任何一项单个RCT，因为排除任何一项单个RCT都不会改变结果。放血疗法可提高CHC患者对IFN治疗的SVR。对此的确认将需要进行详细的治疗前铁研究且有足够效力以证明具有统计学显著性获益的RCT。
