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目的 通过前瞻性、开放性、多中心、随机临床研究,利用早期病毒学应答(EVR)对疗效的预测作用,建立适合我国难治性慢性丙型肝炎(RHC)初治患者的优化治疗方案. 方法 通过18个临床中心纳入438例患者资料,先统一进行聚乙二醇干扰素α联合利巴韦林治疗12周,然后根据完全早期病毒学应答(cEVR)情况分组,获得cEVR的患者进A组继续进行标准治疗至48周;未获得cEVR的患者进入B组:随机进入B1组(继续治疗至72周)和B2组(继续治疗至96周).随访24周.检测患者治疗前后、治疗中和随访中的HCV RNA水平作为疗效评价的指标.用CMH检验或Fisher检验分析各组病毒学应答率的比较. 结果 总的持续病毒学应答(SVR)率为85.1％.其中91.0％的患者获得cEVR进入A组,A组SVR率高达90.8％.B1、B2组间SVR率差异无统计学意义(29.4％比25.0％,P＞0.05).感染基因1型HCV患者的SVR率为83.3％.感染IL28B CC型患者的SVR率为89.8％.本研究中快速病毒学应答(RVR)、cEVR和延迟病毒学应答(DVR)对SVR的阳性预测率分别为93.4％、90.8％和77.8％;RVR、EVR和DVR对SVR的阴性预测率分别为28％、93.3％和100％.治疗过程中,不良反应发生率为66.9％,但严重不良反应发生率仅为1.9％. 结论 中国RHC初治患者中绝大部分(91.0％)可获得cEVR,而通过cEVR分组对RHC初治患者进行个体化治疗的疗效很好,这一治疗方案具有较好的安全性和耐受性.“,”Objective To perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).Methods A total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks.Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment,while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment.Serum hepatitis C virus RNA levels at baseline,treatment weeks 4,12 and 24,end of treatment,and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.Results The overall sustained virological response (SVR) rate was 85.1％.In all,91.0％ of patients achieved cEVR and were assigned to group A,which had an SVR rate of 90.8％.There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4％ vs.25.0％,P ＞ 0.05).The positive PV of rapid virological response (RVR),cEVR and delayed virological response (DVR) for SVR was 93.4％,90.8％ and 77.8％ respectively,and the negative PV of RVR,EVR and DVR for SVR was 28.0％,93.3％ and 100％ respectively.Overall,66.9％ of the patients experienced adverse events (AEs),but only 1.9％ of patients experienced sevcre AEs.Conclusion The majority of Chinese RHC treatmentna(i)ve patients (91.0％) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.