目的 探讨聚乙二醇干扰素(Peg-IFN) α-2a联合利巴韦林抗HCV过程中利巴韦林服用剂量及血药浓度与获得持续病毒学应答(SVR)的关系. 方法 收集了40例接受Peg-IFN α-2a联合利巴韦林抗病毒治疗的慢性丙型肝炎患者(CHC),根据疗效(治疗结束获得病毒学应答患者在停药后随访24周时HCV RNA仍维持低于检测下限为获得SVR,HCV RNA转阳者为复发)分为获得SVR组20例(年龄19 ～ 55岁,男性10例)和复发组20例(年龄21 ～ 76岁,男性12例),采用HPLC-MS/MS测定法检测其治疗过程中第4、12、24、48周的利巴韦林血药浓度.统计学分析采用t检验及受试者工作特征曲线(ROC)分析. 结果 两组患者抗病毒治疗期间服用利巴韦林剂量分别为(15.01±1.21) mg/kg和(10.28±2.81) mg/kg,差异有统计学意义(t=6.908,JP=0.000).AUG达到0.96 (95％CI,0.00～ 1.00),P=0.000,表明利巴韦林服用剂量对获得SVR的预测价值较高.当RBV用量大于13.05 mg/kg(敏感度:100％;特异度:85％)时,更可能获得SVR疗效.获得SVR组第4、12、24、48周RBV血药浓度检测值依次为(1 894.8±740.7)ng/rnl、(2 029.9±547.7) ng/ml、(2 011.8±354.2) ng/ml、(2 093.5±540.3)ng/ml,复发组依次为(1 223.1±722.7) ng/ml、(1 286.9±685.4) ng/ml、(1 304.7±692.0) ng/ml、(1 221.3±655.3)ng/rnl,两组患者每个时间点的利巴韦林血药浓度差异均有统计学意义(依次为t=2.903,P=0.006;t=3.787,P=0.001;t=4.068,P=0.000;t=4.593,P=0.000).采用ROC分析结果显示,第4、12、24、48周曲线下面积依次为0.76(95％CI,0.61 ～ 0.92),P=0.005;0.83 (95％CI,0.68 ～ 0.97),P=0.000;0.83(95％CI,0.69 ～ 0.98),P=0.000;0.86(95％CI,0.72 ～ 1.00),P=0.000;提示利巴韦林血药浓度对SVR有较好的预测价值.第4、12、24、48周利巴韦林血药浓度依次高于1 262.5 ng/ml(截断值,敏感度90％,特异度60％)1 432 ng/ml(敏感度100％,特异度65％)、1 427 ng/ml(敏感度100％,特异度65％)和1 610 ng/ml(敏感度95％,特异度80％)时,获得SVR疗效的可能性更大. 结论 Peg-IFN α-2a联合RBV抗HCV过程中,RBV服用剂量及血药浓度对CHC复发及获得SVR可能性预测价值较高.“,”Objective To investigate the association between the dose and plasma concentration of ribavirin (RBV) and sustained virologic response (SVR) during the anti-hepatitis C virus (HCV) treatment with pegylated interferon-αt-2b (PEG-IFN-αt-2b) and RBV.Methods A total of 40 patients with chronic hepatitis C (CHC) who were treated with PEG-IFN-α-2b and RBV as the antiviral treatment were enrolled,and according to the therapeutic effect (SVR was defined as HCV RNA maintained below the lower limit of detection at 24 weeks after drug discontinuation in patients who achieved virologic response at the end of treatment,and recurrence was defined as HCV RNA turning positive),these patients were divided into SVR group (20 patients aged 19-55 years,including 10 male patients) and recurrence group (20 patients aged 21-76 years,including 12 male patients).The HPLC-MS/MS was used to measure the RBV plasma concentration at weeks 4,12,24,and 48 of treatment.The t-test and receiver operating characteristic (ROC) curve were used for statistical analysis.Results During the antiviral treatment,the dose of RBV showed a significant difference between the two groups (15.01 ± 1.21 mg/kg vs 10.28 ± 2.81 mg/kg,t =6.908,P =0.000).The area under the ROC curve reached 0.96 (95％ CI 0.00-1.00,P =0.000),suggesting that the dose of RBV had a high value in predicting SVR.When the dose of RBV was higher than 13.05 mg/kg (sensitivity 100％;specificity 85％),the possibility of achieving SVR was also increased.The RBV plasma concentrations in the SVR group at weeks 4,12,24,and 48 of treatment were 1 894.8 ± 740.7 ng/ml,2 029.9 ± 547.7 ng/ml,2 011.8 ± 354.2 ng/ml,and 2 093.5 ± 540.3 ng/ml,respectively,and those in the recurrence group were 1 223.1 ± 722.7 ng/ml,1 286.9±±685.4 ng/ml,1304.7 ± 692.0 ng/ml,and 1 221.3 ± 655.3 ng/ml,respectively.The RBV plasma concentration at each time point showed significant differences between the two groups (t =2.903,P =0.006;t =3.787,P =0.001;t =4.068,P =0.000;t =4.593,P =0.000).The results of ROC analysis showed that the areas under the ROC curve at weeks 4,12,24,and 48 of treatment were 0.76 (95％ CI 0.61-0.92,P =0.005),0.83 (95％ CI 0.68-0.97,P =0.000),0.83 (95％ CI 0.69-0.98,P =0.000),and 0.86 (95％ CI 0.72-1.00,P =0.000),respectively,suggesting that the RBV plasma concentration had a high value in predicting SVR.When the cut-offvalues of RBV plasma concentration at weeks 4,12,24,and 48 of treatment were higher than 1262.5 ng/ml (sensitivity 90％;specificity 60％),1432 ng/ml (sensitivity 100％;specificity 65％),1427 ng/ml (sensitivity 100％;specificity 65％),and 1610 ng/ml (sensitivity 95％;specificity 80％),respectively,there was a greater possibility of achieving SVR.Conclusion During the antiviral treatment with PEG-IFN-αt-2b and RBV,the dose and plasma concentration of RBV have a high value in predicting the recurrence of CHC and the possibility of SVR.