不耐受标准治疗方案慢性丙型肝炎患者的低剂量干扰素治疗

Efficacy of low-dose interferon therapy for treating chronic hepatitis C patients who cannot tolerate standard treatment

目的针对不能耐受标准治疗方案的慢陛丙型肝炎（CHC）患者，探索低剂量干扰素联合利巴韦林长期维持治疗的效果，并分析与疗效相关的可能影响因素。方法对于白细胞低下、甲状腺功能异常等多种原因不能耐受标准治疗方案的CHC患者46例，给予个体化低剂量干扰素（标准干扰素60万～300万IU隔日一次，聚乙二醇干扰素50～90μg／周）联合利巴韦林0．6～0．9g／d长期维持治疗，疗程≥72周。连续变量两组间比较采用t检验或秩和检验，计数资料采用χ^2检验或Fisher’s exacttest检验。结果93．5％患者（43／46）可耐受不同低剂量干扰素联合利巴韦林长期维持治疗，只有3例不能耐受而被迫停药。不同节点的病毒学应答率为：快速病毒学应答10．9％、早期病毒学应答30．40／0、24周病毒学应答45．％、48周病毒学应答47．8％。3例患者在治疗过程中肝脏B型超声显示形态学改善。快速病毒学应答、早期病毒学应答、24周病毒学应答者均可在48周时获得较高病毒学应答，尤其24周病毒学应答对48周病毒学应答具有较好预测作用，获得24周病毒学应答者其48周病毒学应答率为95．2％，而24周未获得病毒学应答者其48周未应答率为92．0％。结论（1）对于不能耐受标准治疗方案的CHC患者予以低剂量干扰索联合利巴韦林长期维持治疗，可以获得较高的48周病毒学应答率（47．8％）；（2）24周病毒学应答对48周病毒学应答具有较好预测作用；（3）疗程中严密监测、对症治疗原发病并给予患者足够的依从性教育和心理疏导是治疗得以维持的重要保证。

Objective To investigate the therapeutic efficacy of interferon （IFN） therapy and risk of long-term administration for chronic hepatitis C （CHC） patients who cannot tolerate the standard treatment. Methods Forty-six CHC patients who had proven intolerant to slandard treatments were treated with low-dose IFN （non-pegylated IFN： 60-300MIU QOD, or pegylated IFN： 50-90μg/w） plus ribavirin （RBV; 0.6 g-0.9 g/d） for≥ 72 weeks. Results Forty-three （93.5%） of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects （low white blood cell and platelet counts） that required treatment withdrawal. The virology response rates over treatment time were： rapid virologic response （RVR）： 10.9%; early virus response （EVR）： 30.4%; 24 week virologic response： 45.7%; and, 48 week virologic response： 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who acheived RVR, EVR, or 24weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis. Conclusions Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerate to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis. Conclusions Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerate to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.