翻倍剂量长效干扰素联合利巴韦林治疗无应答慢性丙型病毒性肝炎疗效观察

Therapeutic effect of double-dose pegylated interferon plus ribavirin on chronic hepatitis C in patients with no response to the standard of care

目的探讨翻倍剂量长效干扰素联合利巴韦林治疗原发无应答慢性丙型病毒性肝炎(丙肝)的疗效。方法无应答慢性丙肝患者66例,入组后均行丙肝病毒(hepatitis C virus,HCV)基因型、白细胞介素(interleukin,IL)-28B基因rs12979860位点多态性检测;并给予翻倍剂量长效干扰素(360μg/次,1次/周,皮下注射)联合口服利巴韦林15mg/(kg·d),根据早期病毒学应答(early virological response,EVR)情况决定抗病毒疗程。比较不同HCV基因型、IL-28B基因位点患者持续病毒学应答(sustained virus response,SVR)率、复发率、无应答率。结果 66例中HCV基因1b型57例,HCV基因2a型9例;IL-28Brs12979860位点是CC型19例,CT型23例,TT型24例;基因1b型患者中实现SVR率为31.6%,无应答率为56.1%,复发率为12.3%,基因2a型患者中实现SVR率为22.2%,无应答率为55.6%,复发率为22.2%,不同基因型患者SVR率、复发率、无应答率比较差异均无统计学意义(P>0.05);IL-28B rs12979860位点为CC型患者SVR率为63.16%、复发率为15.79%、无应答率为21.05%,IL-28Brs12979860CT型患者SVR为34.78%、复发率为8.70%,无应答率为56.52%,IL-28Brs12979860TT型患者SVR率为0,复发率为14.67%,无应答率为83.33%,IL-28Brs12979860CC组与TT组,IL-28Brs12979860CT组与TT组SVR率、无应答率比较差异有统计学意义(P<0.05)。结论 IL-28B基因rs12979860位点多态性可预测翻倍剂量长效干扰素联合利巴韦林再治疗无应答慢性丙肝的疗效。

Objective To explore the effects of double-dose pegylated interferon plus ribavirin on primary chronic hepatitis C patients with no response to the standard of care. Methods Sixty-six patients with chronic hepatitis C nonresponsed to the standard of care were detected hepatitis C virus （HCV） genotype and interleukin-28B （IL -28B） rs12979860 single nueleotide polymorphism, and were retreated with subcutaneous injection of double dose of pegylated interferon （360 μg once a week） plus oral administration of ribavirin （15 mg/（kg· d））. The treatment course depended on the early virological response （EVR）. The sustained virus response （SVR）, recurrence rate and nonresponse rate were compared among different HCV RNA and IL-28B single nucleotide polymorphisms. Results In 66 cases, there were 57 eases of HCV-1b and 9 cases of HCV-2a. There were 19 eases of IL-28B rs12979860 site CC type, 23 cases of CT type, 24 cases of TT type. There were no significant differences in SVR, nonresponse rate and recurrence rate between HCV-lb patients （31. 6%, 56. 1%, 12. 3%） and HCV-2a patients （22. 2%, 55. 6%, 22. 2%） （P〉0.05）. SVR, recurrence rate and nonresponse rate were 63.16%, 15.79% and 21.05% in CC type, 34.78%, 8.70% and 56.52% in CT type, and 0, 14.67% and 83.33% in TT type, showing significant differences in SVR and nonresponse rate between CC type and TT type, and between CT type and TT type （P〈0.05）. Conclusion IL-28B rs12979860 single nucleotide polymorphism can predict the effect of double dose of pegylated interferon plus ribavirin on primary chronic hepatitis C patients with no response to the standard of care.