不同疗程聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎复发患者的疗效比较及影响因素

The efficacy and prognostic predictors of different treatment courses with pegylated interferon α-2a and ribavirin combination in recurrent chronic hepatitis C patients

目的研究不同疗程聚乙二醇干扰素α-2a（Peg—IFNα-2a）联合利巴韦林（RBV）对慢性丙型肝炎（CHC）复发患者再次治疗的疗效及影响因素。方法本研究为前瞻性、开放性、多中心、随机临床研究。2009年2月19日至2011年1月17日从16家医院共纳入125例CHC复发患者，随机分入治疗48周（A组）或治疗72周（B组），随访24周。检测患者治疗前、治疗中和随访中的HCVRNA水平作为疗效评价指标。结果所有患者的持续病毒学应答（SVR）为80．0％，复发率为12．2％，两组SVR率（81．3％比78．6％）差异无统计学意义。既往治疗时单独使用干扰素（IFN）组SVR率略高于IFN联合RBV组（92．6％比74．6％），使用普通IFN组SVR率略高于Peg-IFN组（84．7％比71．0％），但差异均无统计学意义。本研究中快速病毒学应答（RVR）和完全早期病毒学应答对SVR的阳性预测值分别为92．3％和86．4％；RVR、早期病毒学应答和延迟病毒学应答对SVR的阴性预测率分别为36．8％、66．7％和100．0％。治疗过程中，不良事件发生率为62．1％，严重不良事件发生率为1．6％。结论Peg—IFNα-2a联合RBV治疗CHC复发患者48周可取得很好的疗效，但未证实延长至72周可进一步提高疗效。治疗12周（判断早期病毒学应答）是预测能否获得SVR最重要的时间点。

Objective To study the efficacy and outcome predictors of combined re-treatment with pegylated interferon （Peg-IFN）α-2a and ribavirin in recurrent chronic hepatitis C （CHC） patients. Methods A muhicenter, prospective, randomized trial was designed. A total of 125 recurrent CHC patients were recruited in 16 clinical centers and randomly assigned into two groups： one was Peg-IFNα-2α combined with ribavirin for 48 weeks （ group A） and the other the same combination for 72 weeks （ group B）. HCV RNA levels in patients＇ serum were detected at baseline, week 4, 12, 24, 48, 72 （group B） after treatment initiation, and 24 weeks after treatment. Results Of all the 90 patients who completed treatment and 24 weeks follow-up, 80.0% achieved sustained virological response （SVR） yet 12. 2% relapsed. There was no significant difference between two groups. The SVR rate in patients previously treated with interferon alone was higher than that in patients with interferon plus ribavirin （92. 6% vs 74. 6% ）, but the difference was of no statistical significance （P = 0.05 ）. Moreover, patients previously treated with common interferon （c-IFN） showed a higher SVR rate than patients with Peg-IFN （84. 7% vs 71.0%, P 〉 0. 05）. The positive predictive value （PV） of rapid virological response（RVR） and complete early virological response for SVR was 92.3% and 86.4% respectively, and the negative PV of RVR, early virological response and delayed virological response for SVR was 36. 8%, 66.7% and 100. 0% respectively. Overall, 62. 1% patients reported adverse events （AEs） and 1.6% patients were severe AEs. Conclusions A high SVR rate has been achieved in recurrent CHC patients who were retreated with Peg- IFNα-2a and ribavirin for 48 weeks. Better SVR cannot be achieved in spite of a prolonged course of 72 weeks. Early virological response at week 12 was the most important predictor for SVR.