普通干扰素治疗失败慢性丙型肝炎患者标准化抗病毒再治疗疗效观察

Efficacy of standard antiviral therapy retreatment following interferon treatment failure in chronic hepatitisC patients

目的对普通干扰素治疗失败的慢性丙型肝炎患者给予标准化抗病毒治疗方案并观察疗效。方法收集2009年1月至2012年6月住院以及门诊就诊的普通干扰素治疗失败慢性丙型肝炎患者资料，给予聚乙二醇干扰素α-2a180μg，每周1次，联合利巴韦林15mg／kg，1次／d，治疗48周。治疗基线状态检测基因分型、HCV RNA。分别于治疗第4、12、24周，治疗结束（48周）和结束后24周（72周）检测HCVRNA。计量资料进行重复测量方差分析，计数资料组间比较采用x_2检验或精确概率检验。结果共收集235例患者资料，经过标准化抗病毒再治疗，235例患者的快速病毒学应答（RVR）、早期病毒学应答（EVR）、治疗结束时病毒学应答（ETVR）、持续病毒学应答（SVR）、复发分别为140例（60．0％）、182例（77．4％）、197例（83．8％）、160例（68％）、37例（15．7％）。复发组患者的RVR、EVR、ETVR、SVR、复发率均高于无应答患者。基因1型HCV感染患者的RVR，EVR、ETVR、复发率均低于非基因1型患者。治疗中实现RVR和EVR的患者最终SVR、ETVR显著高于未实现RVR和EVR患者，复发率却低于未实现RVR和EVR患者。结论普通干扰素治疗失败熳性丙型肝炎患者经过标准化抗病毒再治疗有效率较高，其中病毒基因分型、治疗中病毒学动力学变化是预测疗效重要因素之一。

Objective To investigate the therapeutic efficacy of standard antiviral therapy applied after interferon （IFN） treatment failure in patients with chronic hepatitis C （CHC）. Methods CHC patients who completed a 48-week course of IFN therapy （pegylated （Peg）-IFNct-2a at 180/ag, qw, ih with or without ribavirin （RBV） at 15 mg/kg/w） in our hospital between January 2009 and June 2012 but who showed no response （at week 48） or who relapsed （at week 72） were enrolled in the study. Prior to initiating the 48-week course of retreatment therapy （Peg-IFNct-2a plus RBV as above）, the hepatitis C virus （HCV） genotype was detected and the viral load measured （baseline） by PCR of HCV RNA. Each patient＇s response to therapy was classified as follows： baseline vs. week 4 （rapid virological response, RVR）, vs. weeks 12 and 24 （early virological response, EVR）, vs. week 48 （end of treatment virological response, ETVR） and vs. week 72 （sustained virological response, SVR）. Results Of the total 235 cases administered retreatment therapy, 60.0% （n = 140） achieved RVR, 77.4% （11 = 182） achieved EVR, 83.8% （11 = 197） achieved ETVR, 68.0% （11 = 68%） achieved SVR, and 15.7% （n = 37） relapsed. Stratification analysis of recurrence （n = 158） and non-responsive （11 = 77） sub-groups showed that the recurrence group experienced significantly higher rates of RVR, EVR, ETVR and SVR, but a significantly lower rate of relapse. Stratification analysis of genotype lb carrier （n = 206） and non-lb carrier （n = 29） sub-groupsshowed that the lb carriers had significantly lower rates of RVR, EVR, ETVR and SVR, but a significantly higher rate of relapse. Finally, the patients who achieved RVR （vs. non RVR, n = 95） and EVR （vs. non- EVR, n = 53） showed higher rates of SVR and ETVR. Conclusion CHC patients who fail to respond to the initial course of standard IFN-based therapy may achieve SVR upon retreatment, especially those infected with the HCV genotype lb.