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

张伟; 翟嵩; 杜虹; 景富春; 王丽梅; 张野; 亢必勃; 王九萍; 党双锁; 连建奇; 姜泓

doi:10.3969/j.issn.1001-5256.2023.03.009

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

DOI: 10.3969/j.issn.1001-5256.2023.03.009

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^3, , ,

1.
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

基金项目:

国家自然科学基金面上项目 (81671555)

伦理学声明：本研究于2021年3月8日经空军军医大学第二附属医院伦理委员会批准，批号：202103-038。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：张伟、翟嵩、杜虹、景富春负责实施研究，采集数据，分析/解释数据，起草文稿；王丽梅、张野、亢必勃负责采集数据，分析/解释数据，文稿修改；王九萍、党双锁、连建奇负责技术支持；姜泓负责设计研究，分析/解释数据，修改文章。张伟、翟嵩、杜虹、景富春对本文贡献等同，同为第一作者。

详细信息

通信作者:
姜泓, jiangh518@126.com (ORCID: 0000-0003-2075-3272)

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出版历程
- 收稿日期: 2022-08-27
- 录用日期: 2022-10-08
- 出版日期: 2023-03-20

Efficacy and safety of the 12-week sofosbuvir-coblopasvir regimen in treatment of chronic hepatitis C

1.
Department of Infectious Diseases, The First Affiliated Hospital of Air Force Medical University, Xi'an 710032, China
2.
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
3.
Department of Infectious Diseases, Baoji People's Hospital, Baoji, Shaanxi 721006, China
4.
Department of Infectious Diseases, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China
5.
Department of Microbiology and Pathogenic Biology, School of Basic Medical Sciences, Air Force Medical University, Xi'an 710032, China

Research funding:

National Natural Science Foundation of China (81671555)

More Information

Corresponding author: JIANG Hong, jiangh518@126.com (ORCID: 0000-0003-2075-3272)

摘要

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 RNA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(SVR12)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 RNA均低于检测下限，SVR12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SVR12，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。
- 丙型肝炎, 慢性 /
- 盐酸可洛派韦 /
- 索磷布韦 /
- 治疗结果
Abstract: Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of 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 comparison between groups. Results A 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 genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 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 such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.
- Hepatitis C, Chronic /
- Coblopasvir /
- Sofosbuvir /
- Treatment Outcome

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图 1 患者基因型分布

Figure 1. Genotypes distribution of patients

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图 2 治疗前后生化指标变化

Figure 2. Changes of biochemical indexes before and after treatment

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图 3 治疗前后eGFR变化情况

Figure 3. Changes of eGFR before and after treatment

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表 1 患者基线临床特点

Table 1. Baseline clinical characteristics of patients

指标	总体(n=101)	肝硬化(n=13)	无肝硬化(n=88)
男性[例(%)]	55(54.5)	9(69.2)	47(53.4)
年龄(岁)	53(45.0~59.5)	54(44.0~59.5)	53(45.0~59.8)
≥60岁[例(%)]	24(23.8)	3(23.1)	21(23.9)
TBil(μmol/L)	16.3(12.3~20.2)	20.2(12.4~36.8)	16.1(11.9~19.7)
ALT(U/L)	28(9.8~58.5)	55(11.7~74.0)	23(9.3~52.3)
AST(U/L)	27.0(13.9~58.5)	49.0(15.8~63.0)	25.5(13.9~50.5)
HCV RNA(log₁₀ IU/mL)	6(5.0~6.0)	5(4.5~6.0)	6(5.0~6.0)
eGFR (mL·min^-1·1.73 m^-2)	111.5(94.6~120.0)	113.9(92.2~121.3)	111.0(96.8~120.0)

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表 2 治疗前后生化指标变化

Table 2. Changes of biochemical indexes before and after treatment

组别	基线	治疗12周	Z值	P值
TBil(μmol/L)
全部(n=101)	16.3(12.3~20.2)	15.2(11.4~19.1)	-1.648	0.990
肝硬化(n=13)	20.2(12.4~36.8)	15.0(12.2~29.3)	-0.785	0.433
无肝硬化(n=88)	16.1(11.9~19.7)	15.2(11.2~18.6)	-1.408	0.159
基因3型(n=19)	16.3(8.0~30.8)	16.3(14.1~23.7)	-2.616	0.009
ALT(U/L)
全部(n=101)	28.0(9.8~58.5)	16.0(8.2~31.0)	-5.506	＜0.001
肝硬化(n=13)	55.0(11.7~74.0)	16.2(12.0~38.0)	-2.482	0.013
无肝硬化(n=88)	23.0(9.3~52.3)	15.5(8.0~30.8)	-4.937	＜0.001
基因3型(n=19)	70.0(41.2~110.0)	19.0(13.0~40.0)	-3.703	＜0.001
AST(U/L)
全部(n=101)	27.0(13.9~58.5)	16.2(12.0~38.0)	-1.944	0.052
肝硬化(n=13)	49.0(15.8~63.0)	30.0(17.2~59.5)	-1.682	0.092
无肝硬化(n=88)	25.5(13.9~50.5)	24.5(14.2~37.8)	-1.312	0.189
基因3型(n=19)	69.0(45.0~132.0)	69.0(30.0~132.0)	-1.095	0.273

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表 3 治疗前后eGFR变化

Table 3. Changes of eGFR before and after treatment

组别	例数	eGFR(mL·min^-1·1.73 m^-2)		Z值	P值
组别	例数	基线	治疗12周	Z值	P值
全部	101	111.5(94.6~120.0)	110.0(95.4~120.0)	-0.545	0.586
肝硬化	13	113.9(92.2~121.3)	113.8(94.1~120.0)	-0.454	0.650
无肝硬化	88	111.0(96.8~120.0)	109.8(95.4~120.0)	-0.376	0.707
基因3型	19	120.0(109.6~120.0)	117.9(101.4~120.0)	-1.655	0.098

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表 4 盐酸可洛派韦/索磷布韦不良事件

Table 4. Adverse events of Sofosbuvir/Coblopasvir

不良反应/事件	总体 (n=101)	肝硬化 (n=13)	无肝硬化 (n=88)
全部不良事件[例(%)]	17(16.6)	5(38.5)	12(13.6)
严重不良事件[例(%)]	0	0	0
乏力[例(%)]	13(12.9)	4(30.8)	9(10.2)
恶心[例(%)]	1(1)	0	1(1.1)
失眠[例(%)]	2(1.98)	1(7.7)	1(1.1)
食欲下降[例(%)]	1(1)	0	1(1.1)

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