直接抗病毒药物治疗中国基因1b型慢性丙型肝炎患者的真实世界经验  

Direct acting antiviral agent for Chinese patients with chronic hepatitis C genotype 1b infection——a real world experience

作　　者：纪冬[1] 杨艳东 邵清[1] 李忠斌[1] 廖家杰 陈国凤[1] Ji Dong;Yang Yandong;Shao Qing;Li Zhongbin;Liao Jiajie;Chen Guofeng(Liver Cirrhosis Treatment and Research Center Ⅱ,302 Military Hospital of China, Beijing 100039, China)

机构地区：[1]解放军第三○二医院肝硬化诊疗二中心,北京100039 [2]河北承德围场满族蒙古族自治县医院感染科

出　　处：《中华传染病杂志》2018年第10期605-610,共6页Chinese Journal of Infectious Diseases

基　　金：中华医学会临床医学科研专项基金 (13071110496).

摘　　要：目的评价直接抗病毒药物(direct-actingantiviralagent,DAA)治疗中国基因1b型慢性丙型肝炎(chronichepatitisC,CHC)患者的有效性及安全性。方法选择2014年7月至2016年12月解放军第三○二医院就诊符合抗病毒治疗指征的慢性HCV感染患者233例,采用全口服DAA治疗12周,其中62例给予索磷布韦(sofosbuvir,SOF)联合达拉他韦(daclatasvir,DCV)治疗,171例给予SOF联合来迪帕韦(ledipasvir,LDV)治疗。比较两组患者基线临床特征,治疗的有效性、安全性和耐受性。HCVRNA定量检测采用COBASTaqMan技术(检测下限为15IU/mL),肝弹性值(liverstiffnessmeasurement,LSM)使用FibroScan进行检测。病毒学应答(sustainedvirologicresponse,SVR)率定义为停药12周后HCVRNA低于检测下限。组间比较采用Studentst检验,Pearson卡方检验,Spearman等级相关分析和Fisher确切概率法。结果233例患者中,173例基线HCVRNA≥6.0lgIU/mL,97例LSM≥17.5kPa。两组患者肝脏炎症及肝纤维化程度、HCVRNA的基线水平等差异均无统计学意义(均P>0.05),DAA治疗12周,停药时233例患者HCVRNA均低于检测下限,随访12周有2例复发,SVR12为99.1%。基线LSM越低,HCVRNA下降速度越快(ρ=0.233,P=0.001),SVR12率越高。获得SVR后,SOF+DCV和SOF/LDV组的ALT从治疗基线的(68.0±60.1)和(70.1±56.1)U/L下降至(21.1±10.9)U/L和(15.3±9.5)U/L,TBil从(21.3±17.3)和(18.2±14.0)μmol/L下降至(12.3±6.7)和(10.2±4.6)μmol/L,甲胎蛋白从19.6(10.6,62.3)和15.0(12.0,25.0)μg/L下降至6.5(4.5,18.7)和7.8(5.3,15.4)μg/L,LSM从17.6(8.9,25.4)和15.7(7.8,23.9)kPa下降至13.9(6.5,21.4)和9.1(5.6,19.9)kPa,血清白蛋白从(37.5±5.8)和(38.7±5.5)g/L上升至(41.3±4.7)和(42.8±5.1)g/L,血小板从(120.9±78.2)×109/L和(136.6±65.8)×109/L上升至(139.5±71.8)×109/L和(149.7±71.4)×109/L。所有患者药物不良反应轻微。结论SOF联合DCV或SOF/LDV治疗中国基因1b型CHC患者可获得98%以上的有效率,显著降低LSM值,且安全性良好。Objective To evaluate the effectiveness and safety of direct-acting antiviral agents (DAA) treatment in Chinese chronic hepatitis C (CHC) patients with genotype (GT) 1b HCV infection in a real world setting. Methods The consecutive GT1b CHC Chinese patients treated with sofosbuvir (SOF) plus daclatasvir (DCV) (n=62) or SOF plus ledipasvir (LDV) (n=171) were enrolled from July 2014 to December 2016 at 302 Military Hospital of China. The treatment duration for all the patients was 12 weeks. All the clinical parameters were measured at baseline and then 4-weekly till 12 weeks after the end-of-treatment (EOT). Baseline clinical characteristics, treatment efficacy, safety and tolerance were compared. Serum HCV RNA concentration was detected by means of COBAS TaqMan assay with a lower detection limit of 15 IU/mL, and liver stiffness was measured using FibroScan?. Sustained virologic response (SVR) was defined as HCV RNA under the lower limit of quantification 12 weeks after EOT (SVR12). Students′ t-test, pearson χ2 test, Spearman rank correlation analysis and Fisher exact test were used for comparison between groups when appropriate. Results Among 233 patients, 173 cases had baseline HCV RNA level ≥6.0 lg IU/mL and 97 cases hade liver stiffness measurement (LSM)≥17.5 kPa. The baseline liver inflamation, liver fibrosis, and HCV RNA load of patients in the two groups were not significantly different (all P>0.05). The HCV RNA of all the 233 patients was undetectable at the end of 12-week treatment, while 2 patients relapsed after 12 weeks of EOT with the overall SVR12 of 99.1%. HCV RNA decline was significantly faster in patients with lower LSM than those with higher LSM (ρ=0.233, P=0.001), and SVR12 was higher in those with lower LSM. In terms of other clinical characteristics of SOF+ DCV and SOF+ LVD groups, alanine transaminase declined from (68.0±60.1) and (70.1±56.1) U/L to (21.1±10.9) U/L and (15.3±9.5) U/L, respectively, total bilirubin declined from (21.3±17.3) and (18.2±14.0) μmol/L to (13.2±6.7)

关 键 词：肝炎 丙型 慢性 治疗 直接抗病毒药物 

分 类 号：R512.63[医药卫生—内科学]