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Pegylated interferon-α2a and ribavirin versus pegylated interferon-α2b and ribavirin in chronic hepatitis C : a meta-analysis.

机译:聚乙二醇化干扰素-α2a和利巴韦林与聚乙二醇化干扰素-α2b和利巴韦林在慢性丙型肝炎中的荟萃分析。

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摘要

Results of trials and meta-analyses comparing pegylated interferon (PEG-IFN)-α2a and PEG-IFN-α2b for the treatment of chronic hepatitis C are conflicting.Our objective was to determine which PEG-IFN (α2a or α2b), in association with ribavirin, is the most effective for the treatment of chronic hepatitis C by performing an updated meta-analysis.MEDLINE (1950-2012) and EMBASE (1974-2012) databases, as well as the Cochrane Central Register of controlled trials and the Cochrane Database of Systematic Reviews, were searched. Reference lists of retrieved articles were scanned, and proceedings of major international conferences were manually searched for abstracts. Randomized clinical trials and non-randomized clinical studies comparing PEG-IFN-α2a with PEG-IFN-α2b in association with ribavirin in adult patients with chronic hepatitis C were included. Studies including HIV-positive patients or liver transplant recipients were excluded. The data extraction from each study was conducted independently by two authors, with disagreements resolved by consensus or by a third reviewer. The trial quality of randomized clinical trials was assessed by taking into account generation of allocation sequence, allocation concealment, efficacy of randomization, investigator blindness, description of withdrawals and dropouts and adherence to the intention-to-treat principle. Two meta-analyses were performed, the first including randomized clinical trials only, and the second including both randomized and non-randomized clinical studies. The primary outcome measure was frequency of sustained virological response (SVR). Heterogeneity and publication bias were systematically taken into account.This meta-analysis included 26 studies, 11 randomized and 15 non-randomized, with a total of 18,260 patients: 8,125 treated with PEG-IFN-α2a and 10,135 treated with PEG-IFN-α2b. In the meta-analysis that included randomized trials only, the SVR was significantly higher for patients treated with PEG-IFN-α2a than for those treated with PEG-IFN-α2b for genotypes 1 and 4 [odds ratio (OR) 1.45; 95 % CI 1.09-2.06; p = 0.013] and for all genotypes (OR 1.34; 95 % CI 1.05-1.72; p = 0.02). In the meta-analysis including both randomized and non-randomized studies, the SVR was significantly higher for PEG-IFN-α2a than for PEG-IFN-α2b for all genotypes (OR 1.24; 95 % CI 1.10-1.40; p < 0.001) and for genotypes 1 and 4 (OR 1.25; 95 % CI 1.14-1.36; p < 0.001); for genotypes 2 and 3, the SVR was greater for treatment with PEG-IFN-α2a than with PEG-IFN-α2b, with the difference tending towards significance (OR 1.15; 95 % CI 0.98-1.35; p = 0.08). A certain degree of heterogeneity was present amongst the various studies included in this meta-analysis. Publication bias was detected (particularly for analyses including only randomized controlled trials) and taken into account using appropriate statistical methods.Current evidence suggests that PEG-IFN-α2a and ribavirin is associated with a higher SVR than PEG-IFN-α2b and ribavirin in patients mono-infected with hepatitis C, particularly for genotypes 1 and 4.
机译:比较聚乙二醇干扰素(PEG-IFN)-α2a和PEG-IFN-α2b治疗慢性丙型肝炎的试验和荟萃分析结果相互矛盾。我们的目的是确定联合使用哪种PEG-IFN(α2a或α2b) MEDLINE(1950-2012)和EMBASE(1974-2012)数据库以及对照试验的Cochrane中央登记册和Cochrane联合利巴韦林治疗最有效的治疗慢性丙型肝炎搜索系统评价数据库。扫描检索到的文章的参考清单,并手动搜索大型国际会议的论文摘要。包括在成人慢性丙型肝炎患者中比较PEG-IFN-α2a和PEG-IFN-α2b联合利巴韦林的随机临床试验和非随机临床研究。排除包括HIV阳性患者或肝移植受者在内的研究。每项研究的数据提取均由两名作者独立进行,但意见分歧由共识或第三位审稿人解决。通过考虑分配顺序的产生,分配的隐蔽性,随机化的有效性,研究者的盲目性,对退出和退出的描述以及对意向治疗原则的遵守情况来评估随机临床试验的试验质量。进行了两次荟萃分析,第一项仅包括随机临床试验,第二项包括随机和非随机临床研究。主要结果指标是持续病毒学应答(SVR)的频率。该荟萃分析包括26项研究,11项随机研究和15项非随机研究,总共18,260例患者:8,125例接受PEG-IFN-α2a治疗,10,135例接受PEG-IFN-α2b治疗。在仅包括随机试验的荟萃分析中,对于基因型1和4,接受PEG-IFN-α2a治疗的患者的SVR明显高于接受PEG-IFN-α2b治疗的患者的SVR [比值比(OR)1.45; 95%CI 1.09-2.06; p = 0.013],并且适用于所有基因型(OR 1.34; 95%CI 1.05-1.72; p = 0.02)。在包括随机和非随机研究的荟萃分析中,对于所有基因型,PEG-IFN-α2a的SVR均明显高于PEG-IFN-α2b(OR 1.24; 95%CI 1.10-1.40; p <0.001)对于基因型1和4(OR 1.25; 95%CI 1.14-1.36; p <0.001);对于基因型2和3,用PEG-IFN-α2a处理的SVR大于用PEG-IFN-α2b处理的SVR,差异趋于显着(OR 1.15; 95%CI 0.98-1.35; p = 0.08)。荟萃分析中包括的各种研究中都存在一定程度的异质性。检测到出版偏倚(特别是对于仅包括随机对照试验的分析),并使用适当的统计方法予以考虑。当前证据表明,患者中PEG-IFN-α2a和利巴韦林的SVR高于PEG-IFN-α2b和利巴韦林。感染了丙型肝炎,尤其是基因型1和4。

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