Efficacy and related factors of pegylated interferon α-2a plus ribavirin therapy for chronic hepatitis C in non-responders

目的：观察聚乙二醇干扰素（PegIFN）α-2a联合利巴韦林（RBV）治疗既往无应答的慢性丙型肝炎（ CHC）患者的疗效，并探讨抗病毒治疗的疗程和既往治疗背景对抗病毒疗效的影响。方法采用前瞻性、开放性、多中心、随机对照的方法选择2009年2月至2011年11月10个临床中心共81例CHC既往治疗无应答患者，随机分为A组（37例，PegIFNα-2a联合RBV治疗72周）和B组（44例，PegIFNα-2a联合RBV治疗96周），随访24周。统计两组患者病毒学应答情况，并观察病毒和宿主基因型、既往IFN和RBV使用情况对疗效的影响。采用SAS统计软件进行统计学分析。结果52例患者完成研究，其中A组28例，B组24例。 A组快速病毒学应答（ RVR）、完全早期病毒学应答（cEVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）发生率为25.0％（7／28）、60.7％（17／28）、67.9％（19／28）和60.7％（17／28），B 组分别为41.7％（10／24）、70.8％（17／24）、70.8％（17／24）和70.8％（17／24），两组比较差异无统计学意义（P＞0.05）。 IL-28B CC基因型患者SVR的发生率为82.9％（29／35），高于非CC基因型患者（3／13），差异具有统计学意义（P＜0.01）。既往治疗时是否联合RBV对再次治疗时的病毒学应答率无显著影响（P＞0.05）。既往治疗时使用普通IFN的患者再次治疗后 RVR、cEVR、ETVR和SVR的发生率分别为36.4％（12／33）、81.8％（27／33）、81.8％（27／33）和75.8％（25／33），其中cEVR、ETVR和SVR的发生率明显高于既往使用PegIFN的患者（P＜0.05），而RVR的发生率与既往使用PegIFN的患者比较差异无统计学意义（P＞0.05）。治疗过程中，不良事件发生率为46.9％（38／81），无严重不良事件发生。结论 PegIFNα-2a联合RBV治疗既往治疗无应答的CHC患者可获得满意的疗效。 IL-28B基因型和既往治疗时所使用的IFN类型可影响CHC无应答患者再次治疗时的病毒学应答情况。Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P<0.01).There was no significant difference in viral responses between patients previously treated with IFN plus RBV and those treated by IFN only (P>0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P<0.05), but no significant difference was observed in RVR (P>0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.国家“十一·五”科技重大专项(2008ZX10002013)；国家“十二·五”科技重大专项(2012ZX10002003、2012ZX10002005)；国家“十二·五”重大新药创制科技重大专项中国科技核心期刊(ISTIC)3232-23