真实世界中不同ALT、AST水平慢性丙型肝炎患者对直接抗病毒药物治疗的病毒学应答及肝纤维化指标变化情况

陈宏宇; 亢倩; 罗皓; 谭宁; 潘家莉; 程然; 韩一凡; 杨雨晴; 刘丹; 席宏丽; 于敏; 徐小元

doi:10.3969/j.issn.1001-5256.2021.02.014

真实世界中不同ALT、AST水平慢性丙型肝炎患者对直接抗病毒药物治疗的病毒学应答及肝纤维化指标变化情况

DOI: 10.3969/j.issn.1001-5256.2021.02.014

北京大学第一医院感染疾病科，北京 100034

基金项目:

国家科技重大专项课题艾滋病和病毒性肝炎等重大传染病防治 (2017ZX10302201);

国家科技重大专项课题艾滋病和病毒性肝炎等重大传染病防治 (2017ZX10203202);

消化系统炎性疾病新药临床评价技术平台建设 (2018ZX09201016);

北京市科技计划 (D171100003117005);

北京市科技计划 (D161100002716002);

北京市科技计划 (D161100002716003)

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，特此声明。

作者贡献声明：陈宏宇负责课题设计，资料分析，撰写论文；亢倩、罗皓、谭宁、潘家莉、程然、韩一凡、杨雨晴参与收集数据，修改论文；刘丹、席宏丽、于敏负责收集、检测实验样本；徐小元负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
陈宏宇(1994—)，男，主要从事丙型肝炎相关研究

通信作者:
徐小元，xuxiaoyuan6@163.com

中图分类号: R512.63;R575.2
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出版历程
- 收稿日期: 2020-08-28
- 录用日期: 2020-10-22
- 出版日期: 2021-02-20

Virological response to direct-acting antiviral therapy and changes in liver fibrosis indices in chronic hepatitis C patients with different alanine aminotransferase and aspartate aminotransferase levels in a real-world setting

Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China

摘要

摘要: 目的探讨真实世界中不同ALT、AST水平的慢性丙型肝炎患者对直接抗病毒药物(DAA)治疗的病毒学应答，以及治疗后肝硬度测定(LSM)值、4项因素的肝纤维化指数(FIB-4)和AST/PLT比值指数(APRI)的变化情况。方法纳入2017年12月—2020年5月在北京大学第一医院感染疾病科门诊就诊的慢性丙型肝炎患者，计算患者治疗病毒学应答率。采用Wilcoxon秩和检验对比不同组间基线及治疗结束第12周LSM、FIB-4和APRI的变化；计数资料组间比较采用χ²检验。结果共纳入48例慢性丙型肝炎患者，其中基线ALT或AST出现异常的患者为33.3%。所有患者DAA治疗第4周病毒学应答率为85.4%，治疗结束时、治疗结束12、24、48周均为100%；治疗结束第12周较基线LSM[6.1(5.1~12.4) kPa vs 8.6(5.7~16.9) kPa，Z=-1.676，P=0.043]、APRI[0.24(0.19~0.48) vs 0.42(0.23~1.17)，Z=-2.050，P=0.027]差异有统计学意义。ALT或AST异常的患者治疗结束12周与基线LSM[8.9(5.6~13.1) kPa vs 14.4(8.0~28.2) kPa，Z=-1.679，P=0.047]、APRI[0.44(0.25~0.50) vs 1.29(0.99~2.09)，Z=-3.427，P=0.001]差异有统计学意义。结论慢性丙型肝炎患者DAA治疗后持续病毒学应答率高，基线ALT或AST有异常较无异常的患者在治疗后LSM及APRI改善更明显。
- 丙型肝炎, 慢性 /
- 肝硬化 /
- 抗病毒药 /
- 持续病毒学应答
Abstract: Objective To investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. Methods CHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. Results A total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM [6.1 (5.1-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043] and APRI [0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0.027]. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM [8.9(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047] and APRI [0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001]. Conclusion CHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.
- Hepatitis C, Chronic /
- Liver Cirrhosis /
- Antiviral Agents /
- Sustained Virologic Response

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表 1 患者基线特征

变量	基线ALT或AST无异常(n=32)	基线ALT或AST异常(n=16)	统计值	P值
男/女(例)	13/19	6/10	χ²=0.044	0.835
年龄(岁)	60.5(43.3~70.3)	65.0(49.5~69.0)	Z=-0.698	0.485
ALT(U/L)	22.0(15.0~28.0)	64.0(47.5~104.1)	Z=-4.523	＜0.001
AST(U/L)	24.0(17.4~27.3)	61.2(46.5~91.7)	Z=-5.186	＜0.001
TBil(μmol/L)	11.55(9.48~14.43)	17.35(14.20~26.63)	Z=-1.985	0.047
DBil(μmol/L)	1.87(1.44~3.47)	4.60(2.89~10.61)	Z=-2.554	0.011
血肌酐(μmol/L)	75.00(62.75~85.25)	67.05(52.02~79.50)	Z=-1.019	0.308
eGFR(ml·min^-1·1.73 m^-2)	89.55(67.86~99.38)	90.00(64.27~108.18)	Z=-0.528	0.598
PLT(g/L)	161.0(112.0~229.0)	132.0(113.5~176.5)	Z=-1.504	0.133
LSM(kPa)	6.7(5.3~12.5)	14.4(8.0~28.2)	Z=-2.887	0.003
FIB-4	1.68(0.93~1.93)	4.02(2.54~5.53)	Z=-3.178	0.001
APRI	0.32(0.23~0.45)	1.29(0.99~2.09)	Z=-4.496	＜0.001
HCV RNA(lg IU/ml)	6.44(5.67~7.11)	6.87(6.48~7.30)	Z=-1.973	0.049
基因型(例)			χ²=0.019	0.891
1b	26	14
2a	6	2

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表 2 基线ALT、AST不同状态患者DAA治疗及治疗结束后HCV RNA阴转率比较

组别	治疗4周	治疗12周	结束后12周	结束后24周	结束后48周
基线ALT或AST无异常	30/32(93.8%)	32/32(100.0%)	32/32(100.0%)	27/27(100.0%)	19/19(100.0%)
基线ALT或AST异常	11/16(68.8%)	16/16(100.0%)	16/16(100.0%)	13/13(100.0%)	9/9(100.0%)

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表 3 基线不同ALT、AST水平的患者在DAA治疗后LSM值比较

组别	例数	基线LSM (kPa)	治疗12周LSM (kPa)	结束后12周LSM (kPa)	结束后24周LSM (kPa)
基线ALT或AST无异常	32	6.7(5.3~12.5)	6.7(5.2~11.7)	5.8(4.6~10.6)	7.5(4.9~17.3)
基线ALT或AST异常	16	14.4(8.0~28.2)	9.9(6.4~14.9)	8.9(5.6~13.1)	10.4(5.8~13.9)
Z值		-2.887	-1.261	-0.742	0.883
P值		0.003	0.212	0.470	0.943

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表 4 基线与DAA治疗结束后12周时患者各肝纤维化指标比较

肝纤维化指标	组别	例数	基线	治疗结束12周	Z值	P值
LSM (kPa)	基线ALT或AST无异常	32	6.7(5.3~12.5)	5.8(4.6~10.6)	-0.232	0.817
	基线ALT或AST异常	16	14.4(8.0~28.2)	8.9(5.6~13.1)	-1.679	0.047
	所有患者	48	8.6(5.7~16.9)	6.1(5.1~12.4)	-1.676	0.043
FIB-4	基线ALT或AST无异常	32	1.68(0.93~1.93)	1.42(0.97~2.20)	-0.308	0.758
	基线ALT或AST异常	16	4.02(2.54~5.53)	2.71(1.26~4.10)	-1.736	0.082
	所有患者	48	1.74(1.00~4.16)	1.42(1.09~2.78)	-0.749	0.230
APRI	基线ALT或AST无异常	32	0.32(0.23~0.45)	0.23(0.17~0.37)	-1.491	0.136
	基线ALT或AST异常	16	1.29(0.99~2.09)	0.44(0.25~0.50)	-3.427	0.001
	所有患者	48	0.42(0.23~1.17)	0.24(0.19~0.48)	-2.050	0.027

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参考文献(11)

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