索磷布韦/维帕他韦联合或不联合利巴韦林治疗基因3型慢性丙型肝炎病毒感染者的疗效及安全性:一项真实世界研究

目的评估索磷布韦/维帕他韦(sofosbuvir/velpatasvir,SOF/VEL)联合或不联合利巴韦林(ribavirin,RBV)治疗基因3型慢性丙型肝炎病毒(hepatitis c virus,HCV)感染者的有效性及安全性。方法以2018年12月至2020年1月至成都市公共卫生临床医疗中心就诊的84例基因3型慢性HCV感染者为研究对象,其中慢性丙型肝炎56例,代偿期肝硬化17例,失代偿期肝硬化11例。根据患者病情予以SOF/VEL联合或不联合RBV抗病毒治疗12~24周,检测患者基线、治疗4周、治疗结束时以及治疗结束后12周肝功能丙氨酸氨基转移酶(alanine transaminase,ALT)、天门冬氨酸氨基转移酶(aspartate transaminase,AST)、总胆红素(total bilirubin,TBil)、白蛋白(albumin,ALB)]、肾功能尿素、肌酐(creatinine,Cr)]和血常规白细胞(white blood cell,WBC)、血红蛋白(hemoglobin,HGB)和血小板(platelet,PLT)]等指标,检测基线和治疗结束后12周的肝硬度值。同时详细记录患者在治疗期间的不良事件。主要结局指标为治疗结束后12周的持续病毒学应答(sustained virological response,SVR)和治疗中不良事件的发生情况。结果共80例患者(95.2%)达到SVR12,其中慢性丙型肝炎、代偿期肝硬化及失代偿期肝硬化患者的SVR12分别为100%(56/56)、94.1%(16/17)和72.7%(8/11),差异有统计学意义(P=0.003)。慢性丙型肝炎组、代偿期肝硬化及失代偿期肝硬化患者治疗结束后12周肝硬度值均较基线显著降低(6.7±0.7)kPa vs(7.4±1.1)kPa,(17.8±3.1)kPa vs(25.9±3.4)kPa,(23.0±4.5)kPa vs(31.0±4.9)kPa;P均<0.001]。3组患者治疗后ALT和AST均较基线显著降低(P均<0.05),尿素、Cr、WBC和PLT差异无统计学意义(P均>0.05)。代偿期肝硬化和失代偿期肝硬化患者治疗后ALB较基线显著升高,HGB较基线显著降低(P均<0.05)。84例患者总体不良事件发生率为13.1%(11/84),其中慢性丙型肝炎、代偿期肝硬化和失代偿期肝硬化患者不良事件发生率分别为8.9%(5/56)、11.8%(2/17)和36.4%(4/11),差异无统计学意义(P=0.055),常见的不良事件包括疲劳、头痛和贫血等,无严重不良事件发生,无因不良事件导致的治疗中止。结论应用SOF/VEL联合或不联合RBV方案治疗基因3型慢性HCV感染者具有较高的SVR12,不良事件发生率较低,疗效显著,安全性良好。

Efficacy and safety of Sofosbuvir/Velpatasvir with or without ribavirin in treatment of patients with chronic hepatitis C virus genotype 3 infection:a real-world study

Objective To evaluate the efficacy and safety of Sofosbuvir/Velpatasvir(SOF/VEL)with or without ribavirin(RBV)in treatment of patients with chronic hepatitis C virus(HCV)genotype 3 infection.Methods A total of 84 patients with chronic HCV genotype 3 infection from December 2018 to January 2020 in Public Health Clinical Center of Chengdu were selected.Among them,56 cases were with chronic hepatitis C,17 cases were with compensated cirrhosis and 11 cases were with decompensated cirrhosis.The patients were given SOF/VEL with or without RBV antiviral therapy for 12~24 weeks according to their conditions.Liver functionalanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil)and albumin(ALB)],renal functionurea and creatinine(Cr)]and routine blood indexeswhite blood cell(WBC),hemoglobin(HGB)and platelet(PLT)]of patients were detected at baseline,4 weeks of treatment,at the end of treatment and 12 weeks after the end of treatment.Liver stiffness value of patients were detected at baseline and 12 weeks after the end of treatment.The occurrence of adverse events during the treatment were recorded in detail.The primary outcome measures were the sustained virological response(SVR)12 weeks post-treatment and adverse events during the treatment.Results A total of 80 patients(95.2%)achieved SVR12,the SVR12 rates of patients in chronic hepatitis C group,compensated cirrhosis group and decompensated cirrhosis group were 100%(56/56),94.1%(16/17)and 72.7%(8/11),respectively,the difference was statistically significant(P=0.003).The liver stiffness values of patients in chronic hepatitis C group,compensated cirrhosis group and decompensated cirrhosis group after treatment were significantly lower than those at baseline(6.7±0.7)kPa vs(7.4±1.1)kPa,(17.8±3.1)kPa vs(25.9±3.4)kPa,(23.0±4.5)kPa vs(31.0±4.9)kPa;all P<0.001].The ALT and AST levels of patients in three groups after treatment were significantly lower than those at baseline(all P<0.05),and there were no statistically significant differences in urea,Cr,WBC and PLT(all P>0.05).Compared with those at baseline,the ALB level of patients in compensated cirrhosis group and decompensated cirrhosis group increased significantly and HGB decreased significantly(all P<0.05).The overall incidence of adverse events of the 84 patients was 13.1%(11/84),the incidence of adverse events in chronic hepatitis C group,compensated cirrhosis group and decompensated cirrhosis group were 8.9%(5/56),11.8%(2/17)and 36.4%(4/11),respectively,the difference was not statistically significant(P=0.055).The most common AE were fatigue,headache and anemia,no serious AE occurred,and no treatment was discontinued due to AE.Conclusions The application of SOF/VEL with or without RBV in treatment of patients with chronic HCV genotype 3 infection has higher SVR12,lower incidence of AE,with significant efficacy and good safety.