直接抗病毒药物治疗慢性丙型肝炎的临床疗效观察

Clinical effect of direct-acting antiviral agents for chronic hepatitis C

目的评估直接抗病毒药物(DAA)治疗慢性丙型肝炎的临床效果及安全性。方法入组106例慢性丙型肝炎患者,HCV RNA均为阳性,病毒载量为5.955e×10~4～1.688e×10~8 IU/mL,其中基因1b型与2a型分别是62例、44例,并有11例肝硬化肝功能失代偿患者均为1b型。对于1b型无肝硬化以及2a型的慢性丙型肝炎采用索菲布韦联合达卡他韦治疗,1b型肝硬化患者加用利巴韦林,疗程12周。1b型肝硬化肝功能失代偿患者不能耐受利巴韦林,延长疗程至24周。治疗过程中观察HCV RNA、肝功能、凝血功能、血常规及药物的安全性。结果 58.5%的患者获得超快速病毒学应答(SRVR)(1周),99%的患者在治疗4周时获得完全病毒学应答,疗程结束时病毒应答率为99%;治疗前后对照ALT,AST下降至正常范围(P<0.05)、肝硬化组Alb升高(P<0.05),但TBil治疗前后的变化不明显,差异无统计学意义(P>0.05);随访12和24周时持续病毒学应答高(SVR12、SVR24均为99%),不良反应轻微且出现率不高,例如胃肠不适(2例),头痛(5例),乏力、腹胀(10例)。结论索菲布韦联合达卡他韦治疗慢性丙型肝炎安全性好、不良反应低、疗效肯定。对慢性丙型肝炎的远期疗效有待进一步观察。

Objective To evaluate the clinical efficacy and safety of direcl acting antiviral agents （DAAs） in patients with chronic hepatitis C. Methods A total of 106 patients with chronic hepatitis C were enrolled in this study. Age of the patients were from 29 to 74 years olcl with a median age of 56. Hepatitis C virus （HCV） RNA was detected in all patients, with the viral loacl ranging from 5. 955e ×10^4 to 1. 688e ×10^8 IU/ml. Among the 106 patients, 62 were genotype lb and 44 were genotype 2a. Moreover, 11 patients with deeompensated cirrhosis were all infected with HCV genotype lb. All patients were treated with sofosbuvir （SOF） and daelatasvir （DCV） for 12 weeks, and ribavirin was added in patients with HCV genotype lb and cirrhosis. Patients with HCV genotype lb and deeompensated liver cirrhosis could not tolerate ribavirin, so their treatment was extended to 24 weeks. HCV RNA, liver function, safety and adverse events were observed during and after treatment. Results Of all the patients, 58.5% achieved superapid virological response at week 1 of treatment, 99% achieved complete virological response at weeks 4 of treatment, and 99% achieved viral response at the end of treatment. After treatment, levels of alanine aminotransferase and aspartate aminotransferase were normalized （P〈0.05）. Level of albumin was increased in cirrhosis group （P〈0.05）, while level of total bilirubin showed no statistical difference （P〈0.05）. The rate of sustained virological response （SVR） at weeks 12 and week 24 after treatmenl was high （ both were 99%）. Only slight adverse effects appeared such as gastrointestinal discomfort （2 cases）, headache （5 cases）, and fatigue with bloating （10 cases）. Conclusion Combined therapy of SOF and DCV for patients with HCV is safe and effective. However, the long-term therapeutic efficacy needs to be further investigated.