直接作用抗病毒药物治疗慢性HCV感染者的初步临床分析

Preliminary clinical analysis of direct-acting antiviral agents in patients with chronic hepatitis C virus infection

目的观察直接作用抗病毒药物(direct-acting antiviral agents,DAAs)治疗我国慢性丙型肝炎病毒(hepatitis C virus,HCV)感染者的疗效和安全性。方法回顾性分析2015年1月至2016年1月于首都医科大学附属北京地坛医院就诊并使用DAAs抗病毒治疗的慢性丙型肝炎和丙型肝炎肝硬化患者的临床特点及治疗方案,观察治疗过程中患者HCV RNA载量、肝功能、生物化学指标及不良反应。结果共纳入64例患者,平均年龄(51.91±11.32)岁,HCV RNA载量为1.63×103~2.72×107 IU/ml。其中慢性丙型肝炎患者41例,丙型肝炎肝硬化患者23例(失代偿期肝硬化11例);初治患者28例,干扰素经治患者36例;HCV RNA基因分型1b型46例,2a型14例,3a型2例,3b型2例。治疗方案为sofosbuvir+daclatasvir+利巴韦林(ribavirin,RBV)17例、sofosbuvir+daclatasvir 10例、sofosbuvir+ledipasvir+RBV 15例、sofosbuvir+ledipasvir 11例、sofosbuvir+RBV 9例、sofosbuvir+聚乙二醇化干扰素(pegylated interferons,Peg IFN)+RBV 2例。除1例失代偿期丙型肝炎肝硬化患者在治疗过程中因消化道出血死亡外,其余63例患者均完成了治疗并已停药随访24周以上,所有患者均获得快速病毒学应答(rapid virological response,RVR)和治疗结束时病毒学应答(end of treatment virological response,ETVR),62例患者获得持续病毒学应答(sustained virologic response,SVR)。抗病毒治疗后ALT、AST和甲胎蛋白(alpha fetoprotein,AFP)水平显著下降(z=-6.10,P<0.001;z=-6.15,P<0.001;z=-3.18,P=0.001),白蛋白(albumin,ALB)和胆碱酯酶(cholinesterase,CHE)水平显著升高(t=-2.75,P=0.008;t=-3.20,P=0.002),肾功能无减退。不良反应轻,均可自行缓解,不影响治疗。结论 DAAs治疗我国慢性丙型肝炎及丙型肝炎肝硬化患者疗效肯定,安全性好,对失代偿期丙型肝炎肝硬化患者的远期疗效有待进一步观察。

Objective To investigate the clinical efficacy and safety of direct-acting antiviral agents （DAAs）in patients with chronic hepatitis C virus （HCV） infection in China. Methods The clinical characteristicsand treatment protocols of patients with chronic hepatitis C and HCV-related liver cirrhosis in Beijing DitanHospital, Capital Medical University from January 2015 to January 2016 were analyzed by descriptive method.HCV RNA, liver function, safety and adverse reactions were observed during the treatment. Results Total of64 cases were enrolled in this study. The average age was （51.91 ± 11.32） years. Total of 41 patients were withchronic hepatitis C and 23 patients were with HCV-related liver cirrhosis （11 cases were with decompensatedcirrhosis）. Total of 28 patients were initially treated while 36 patients were treated with interferon previously.HCV RNA load ranged from 1.63 × 103 IU/ml to 2.72 × 107 IU/ml. Total of 46 cases were genotype 1b, 14 caseswere genotype 2a, 2 cases were genotype 3a and 2 cases were genotype 3b. All patients were treated with DAAs,of whom 17 cases were treated with sofosbuvir ＋ daclatasvir ＋ ribavirin （RBV）, 10 cases were treated withsofosbuvir ＋ daclatasvir, 15 cases were treated with sofosbuvir ＋ ledipasvir ＋ RBV, 11 cases were treated withsofosbuvir ＋ ledipasvir, 9 cases were treated with sofosbuvir ＋ RBV and 2 cases were treated with sofosbuvir ＋pegylated interferon （PegIFN） ＋ RBV. Total of 63 patients completed the treatment and followed for 24 weeksafter drug withdrawal while one case was died of gastrointestinal bleeding during the treatment. All patientsachieved rapid virological response （RVR） and end treatment virological response （ETVR）, and 62 patientsachieved sustained virologic response （SVR）. Aftrer treatment, the levels of ALT, AST and alphafetoprotein （AFP）decreased significantly （z = -6.10, P 〈 0.001; z = -6.15, P 〈 0.001; z = -3.18, P = 0.001） while albumin （ALB）and cholinesterase （CHE） increased significantly （t = -2.75, P = 0.008; t = -3.20, P = 0.002）. No obvious changeof renal function was found. Only slight adverse reactions were observed during treatment. These discomfortswere transient and alleviate by themselves, which did not affect the treatment. Conclusions DAAs are effectiveand safe in treatment of patients with chronic hepatitis C and HCV-related liver cirrhosis in China. Fordecompensated HCV-related liver cirrhosis patients, the long-term therapeutic efficacy needs furtherly evaluated.