Cammà Calogero, Cabibbo Giuseppe, Bronte Fabrizio, Enea Marco, Licata Anna, Attanasio Massimo, Andriulli Angelo, Craxì Antonio
Cattedra di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
J Hepatol. 2009 Oct;51(4):675-81. doi: 10.1016/j.jhep.2009.06.018. Epub 2009 Jul 15.
BACKGROUND/AIMS: Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.
MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in the meta-analysis. Data on study populations, interventions, and outcomes were extracted from trials using a random-effects model. Primary outcome was the SVR rate.
The pooled estimate of SVR rate was 16.3% (95% Confidence Interval - 95% CI, 8.3-29.6%). There was a significant heterogeneity among studies (p<0.0001). Heterogeneity was less apparent in studies that included fewer patients with cirrhosis or overweight. By meta-regression, higher SVR rate was observed in trials with a lower prevalence of subjects with genotype 1 infection and with fewer overweight patients. The use of a 24-week retreatment stopping rule did not affect SVR rate.
The overall modest efficacy argues against an indiscriminate retreatment with PEG-IFN and ribavirin of all non-responders. Restricting retreatment to non-overweight patients or to those with genotype 2 or 3 infection, using a 24-week retreatment stopping rule, would optimize the potential benefit with a scarce likelihood of missing a curative response.
背景/目的:在各项研究中已评估了聚乙二醇化干扰素(PEG-IFN)联合利巴韦林对标准或聚乙二醇化干扰素联合利巴韦林治疗无应答者进行再治疗的疗效,但持续病毒学应答(SVR)率各不相同,影响疗效和耐受性的因素仍未完全明确。我们旨在通过这项荟萃分析关注SVR率并确定影响其的因素。
使用MEDLINE以及手工检索。纳入的研究需为对照或非对照试验、已发表的全文论文,且纳入标准或聚乙二醇化干扰素及利巴韦林治疗的无应答者。荟萃分析纳入了14项试验。使用随机效应模型从试验中提取有关研究人群、干预措施和结局的数据。主要结局为SVR率。
SVR率的合并估计值为16.3%(95%置信区间 - 95%CI,8.3 - 29.6%)。各研究之间存在显著异质性(p<0.0001)。在肝硬化患者或超重患者较少的研究中,异质性不太明显。通过荟萃回归分析,在基因型1感染患病率较低且超重患者较少的试验中观察到较高的SVR率。采用24周再治疗停药规则不影响SVR率。
总体疗效一般,不支持对所有无应答者不加区分地使用PEG-IFN和利巴韦林进行再治疗。将再治疗限制于非超重患者或基因型2或3感染患者,采用24周再治疗停药规则,将在极少错过治愈性应答可能性的情况下优化潜在获益。