12周索磷布韦联合可洛派韦...丙型肝炎的效果和安全性分析_张伟.pdf

病毒性肝炎DOI:10 3969/j issn1001 5256 2023 03 00912 周索磷布韦联合可洛派韦治疗慢性丙型肝炎的效果和安全性分析张伟1，翟嵩2，杜虹3，景富春4，王丽梅5，张野3，亢必勃3，王九萍1，党双锁2，连建奇3，姜泓31 空军军医大学第一附属医院 感染性疾病科，西安 710032;2 西安交通大学第二附属医院 感染科，西安710004;3 陕西省宝鸡市人民医院 感染科，陕西 宝鸡 721006;4 空军军医大学第二附属医院 感染科，西安 710038;5 空军军医大学基础医学院 微生物学与病原生物学教研室，西安 710032通信作者:姜泓，jiangh518126 com(OCID:0000 0003 2075 3272)摘要:目的分析索磷布韦联合盐酸可洛派韦 12 周方案治疗中国西北地区慢性丙型肝炎的效果和安全性。方法本研究纳入2021 年7 月1 日2021 年12 月31 日空军军医大学第一附属医院、空军军医大学第二附属医院、西安交通大学第二附属医院、陕西省宝鸡市中心医院 4 家医院的慢性丙型肝炎(CHC)接受索磷布韦(400 mg)联合盐酸可洛派韦(60 mg)治疗 12 周的 101 例患者，其中肝硬化 13 例，无肝硬化 88 例。无论是否有肝硬化、任何基因分型均未加用利巴韦林等其他抗病毒药物。提取患者基线、治疗 12 周及停药后 12 周的 HCV NA 定量、肝生化指标等临床资料。主要评估治疗结束后 12 周持续病毒学应答(SV12)和治疗 12 周时的安全性。其次评估治疗 12 周对肝生化指标的影响。不满足正态分布的计量资料采用 M(P25 P75)表示，两组间比较采用 Mann Whitney U 检验。结果共 101 例患者纳入分析，其中男性 55 例(54 5%)，中位年龄 53 岁，12 8%有肝硬化，1 0%合并肝癌，3 0%为经治患者，3 0%合并有 2 型糖尿病。基因型分布:1 型 8%，2 型 60%，3 型 19%，6 型 6%，未检测基因型 7%。101 例患者经 12 周治疗HCV NA 均低于检测下限，SV12 达 100%，与基线相比治疗 12 周血清 ALT 水平明显降低(P 0 05)。有阿托伐他汀钙、阿司匹林、二甲双胍、硝苯地平、双环醇、复方甘草酸苷等合并用药的患者为 22 7%。任何不良事件发生率为16 8%，疲乏(12 9%)最常见。结论12 周索磷布韦联合盐酸可洛派韦治疗西北地区 CHC 患者可获得较高的SV12，抗病毒治疗安全性良好，治疗 12 周时患者血清 ALT 异常明显改善。关键词:丙型肝炎，慢性;盐酸可洛派韦;索磷布韦;治疗结果基金项目:国家自然科学基金面上项目(81671555)Efficacy and safety of the 12 week sofosbuvir coblopasvir regimen in treatment of chronic hepatitis CZHANG Wei1，ZHAI Song2，DU Hong3，JING Fuchun4，WANG Limei5，ZHANG Ye3，KANG Bibo3，WANG Jiuping1，DANGShuangsuo2，LIAN Jianqi3，JIANG Hong3(1 Department of Infectious Diseases，The First Affiliated Hospital of Air ForceMedical University，Xi an 710032，China;2 Department of Infectious Diseases，The Second Affiliated Hospital of Xi an Jiao-tong University，Xi an 710004，China;3 Department of Infectious Diseases，Baoji People s Hospital，Baoji，Shaanxi721006，China;4 Department of Infectious Diseases，The Second Affiliated Hospital of Air Force Medical University，Xi an710038，China;5 Department of Microbiology and Pathogenic Biology，School of Basic Medical Sciences，Air Force MedicalUniversity，Xi an 710032，China)Corresponding author:JIANG Hong，jiangh518126 com(OCID:0000 0003 2075 3272)Abstract:ObjectiveTo investigate the efficacy and safety of the 12 week regimen with sofosbuvir and coblopasvir hydro-935张伟，等 12 周索磷布韦联合可洛派韦治疗慢性丙型肝炎的效果和安全性分析chloride in the treatment of chronic hepatitis C(CHC)in northwest China MethodsThis study enrolled 101 patients withCHC of any genotype who received sofosbuvir(400 mg)combined with coblopasvir hydrochloride(60 mg)for 12 weeks in TheFirst Affiliated Hospital of Air Force Medical University，The Second Affiliated Hospital of Air Force Medical University，TheSecond Affiliated Hospital of Xi an Jiaotong University，and Baoji Central Hospital from July 1 to December 31，2021，amongwhom 13 had liver cirrhosis and 88 did not have live cirrhosis Other antiviral drugs such as ribavirin were not added regardlessof the presence or absence of liver cirrhosis or the genotype of CHC elated clinical data ere extracted，including HCV NAquantification and liver biochemical parameters at baseline，at week 12 of treatment，and at 12 weeks after drug withdrawalThe primary endpoints were sustained virologic response at 12 weeks after the end of treatment(SV12)and safety at week 12of treatment，and the secondary endpoint was the effect of the 12 week treatment on liver biochemical parameters The non normally distributed continuous data were expressed as M(P25 P75)，and the Mann Whitney U test was used for comparisonbetween groups esultsA total of 101 patients were included in the analysis，among whom there were 55 male patients(54 5%)and 46 female patients，and the median age was 53 years Among these patients，12 8%had liver cirrhosis，1 0%had liver cancer，3 0%were treatment experienced patients，and 3 0%had type 2 diabetes As for genotype distribution，8%had CHC genotype 1，60%had CHC genotype 2，19%had CHC genotype 3，and 6%had CHC genotype 6，and geno-type was not tested for 7%of the patients After 12 weeks of treatment，all 101 patients had a HCV NA level of below thelower limit of detection and an SV12 rate of 100%，with a significant reduction in the serum level of alanine aminotransferase(ALT)from baseline to week 12 of treatment(P 0 05)Among these patients，22 7%had concomitant medications suchas atorvastatin calcium，aspirin，metformin，nifedipine，bicyclol，and compound glycyrrhizin The incidence rate of adverseevents was 16 8%，and fatigue(12 9%)was the most common adverse event ConclusionThe 12 week treatment withsofosbuvir and coblopasvir hydrochloride can obtain high SV12 in CHC patients in northwest China and has good antiviralsafety，with a significant improvement in abnormal serum ALT at week 12 of treatmentKey words:Hepatitis C，Chronic;Coblopasvir;Sofosbuvir;Treatment Outcomeesearch funding:National Natural Science Foundation of China(81671555)慢性丙型肝炎(CHC)是引起肝硬化、肝细胞癌(HCC)的重要原因，相关的肝病导致全球每年约39 9 万例患者死亡1 2。直接抗病毒药物(DAA)主要作用于非结构蛋白 NS3/4A 蛋白酶、NS5A 和NS5B 聚合酶3。2013 年以来，多种 DAA 进入临床，在CHC 治疗领域全面取代干扰素联合利巴韦林(P)，成为治愈 CHC 最重要的药物 4 5。NS5B NA 依赖的NA 聚合酶在 HCV 复制过程中发挥了重要作用，是DAA 作用的重要靶点，多种 DAA 联合治疗方案包含有NS5B 抑制剂。中国 CH