Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Denmark.
Aliment Pharmacol Ther. 2010 Oct;32(7):840-50. doi: 10.1111/j.1365-2036.2010.04423.x.
Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C.
To meta-analyse the effect of adding ribavirin to interferon for chronic hepatitis C.
The results of randomized trials were combined in cumulative meta-analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver-related morbidity plus all-cause mortality.
We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64-0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P-value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes.
The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes.
已经发表了多项关于慢性丙型肝炎抗病毒治疗的随机试验。
对聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的效果进行荟萃分析。
将随机试验的结果合并进行累积荟萃分析。采用试验序贯分析来调整因随机误差和多重性而产生的虚假结果。结局指标为血清中不可检测的丙型肝炎病毒 RNA（持续病毒学应答）和肝脏相关发病率加全因死亡率。
我们纳入了 82 项随机试验，共 12615 例患者。试验序贯分析在 1998 年 9 项试验后确立了干扰素联合利巴韦林与干扰素相比在持续病毒学应答方面的明确有益效果（RR：0.74；95%CI：0.64-0.85，P<0.0001，1734 例患者）。随后，又发表了 73 项试验，只是进一步缩小了置信区间并降低了 P 值。相比之下，试验序贯分析发现，需要更多的证据来令人信服地检测干扰素联合利巴韦林与干扰素单药治疗对临床结局的有益效果。
最近几项关于在慢性丙型肝炎中添加利巴韦林的临床试验的理论依据是值得商榷的，因为其在病毒学反应方面的效果已经确立。需要更多的证据来评估在干扰素中添加利巴韦林是否能改善临床结局。
