经治慢性乙型肝炎患者低病毒血症发生率和影响因素的Meta分析

谢露; 刘亚楠; 刘光伟; 李鹏宇; 胡新宁; 康秋佳; 郭会军

doi:10.12449/JCH240709

经治慢性乙型肝炎患者低病毒血症发生率和影响因素的Meta分析

DOI: 10.12449/JCH240709

谢露^{1a, 2},
刘亚楠^{1a, 2},
刘光伟^1b,
李鹏宇^{1a, 3},
胡新宁^{1a, 2},
康秋佳^{1a, 2},
郭会军^{1a, 3, , ,}

1a.
河南中医药大学第一附属医院艾研中心，郑州 450000
1b.
河南中医药大学第一附属医院脾胃肝胆科，郑州 450000
2.
河南中医药大学第一临床医学院，郑州 450046
3.
河南省病毒性疾病中医药防治重点实验室，郑州 450000

基金项目:

中原英才计划（育才系列） (ZYYCYU202012119)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：谢露负责设计论文框架，起草论文；谢露、刘亚楠负责文献检索，筛选及数据提取，统计分析和绘制图表；胡新宁、康秋佳负责数据核对和图表优化；李鹏宇、刘光伟负责修改论文；郭会军负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
郭会军， guo.6268505@163.com （ORCID： 0000-0002-2326-4952）

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出版历程
- 收稿日期: 2023-10-17
- 录用日期: 2023-11-30
- 出版日期: 2024-07-25

Incidence rate of low-level viremia and related influencing factors in treatment-experienced chronic hepatitis B patients： A Meta-analysis

Lu XIE^{1a, 2},
Yanan LIU^{1a, 2},
Guangwei LIU^1b,
Pengyu LI^{1a, 3},
Xinning HU^{1a, 2},
Qiujia KANG^{1a, 2},
Huijun GUO^{1a, 3
, ,
,}

1a.
AIDS Clinical Research Center The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China
1b.
Spleen，Stomach and Hepatobiliary Department The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000，China
2.
The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450046，China
3.
Henan Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Viral Diseases，Zhengzhou 450000，China

Research funding:

Zhongyuan Talent Project （Yucai Series） (ZYYCYU202012119)

More Information

Corresponding author: GUO Huijun， guo.6268505@163.com （ORCID： 0000-0002-2326-4952）

摘要

摘要: 目的系统评价慢性乙型肝炎（CHB）患者低病毒血症（LLV）的发生率及其影响因素，为临床有效干预和预防LLV的发生提供循证医学证据。方法本研究根据PRISMA指南完成，PROSPERO注册号：CRD42023455304。计算机检索中国知网、万方数据库、维普、中国生物医学文献服务系统、PubMed、Embase、Web of Science、Cochrane Library中有关CHB患者LLV发生及影响因素的观察性研究，检索时间为建库至2023年7月21日。应用Stata 16.0软件进行Meta分析。结果共纳入文献12篇，总样本量3 408例，包括LLV患者1 181例。Meta分析结果显示，经治CHB患者LLV发生率为32.8%（95%CI：27.6%～38.3%）；HBsAg定量高（OR=2.107，95%CI：1.782～2.491，P<0.001）、HBeAg阳性（OR=3.258，95%CI：2.629～4.038，P<0.001）、高基线HBV DNA水平（OR=1.286，95%CI：1.157～1.430，P<0.001）及有恩替卡韦治疗史（OR=3.089，95%CI：1.880～5.074，P<0.001）是LLV发生的危险因素；抗病毒时间≥3年（OR=0.175，95%CI：0.093～0.331，P<0.001）和高基线ALT水平（OR=0.985，95%CI：0.978～0.992，P<0.001）是LLV的保护因素。敏感性分析显示效应值未发生明显变化，提示Meta分析结果相对稳定。纳入研究漏斗图基本对称，Egger’s检验和Begg’s检验结果提示纳入文献不存在明显发表偏倚。结论临床医生应根据LLV的影响因素，综合临床证据有效指导决策，降低远期临床风险，避免不良结局。
- 乙型肝炎，慢性 /
- 低病毒血症 /
- Meta分析
Abstract: Objective To systematically evaluate the incidence rate of low-level viremia （LLV） in chronic hepatitis B （CHB） patients and related influencing factors， and to provide evidence-based medicine evidence for effective intervention and prevention of LLV in clinical practice. Methods This study was conducted according to the PRISMA guideline， with a PROSPERO registration number of CRD42023455304. CNKI， Wanfang Data， VIP， SinoMed， PubMed， Embase， Web of Science， and the Cochrane library were searched for observational studies on LLV and related influencing factors in CHB patients published up to July 21， 2023. Stata 16.0 software was used to perform the meta-analysis. Results A total of 12 articles were included， with a total sample size of 3408 cases， among whom there were 1181 patients with LLV. The meta-analysis showed that the incidence rate of LLV was 32.8% （95% confidence interval ［CI］： 27.6%‍ ‍—‍ ‍38.3%） in treatment-experienced CHB patients. High HBsAg quantification （odds ratio ［OR］=2.107， 95%CI： 1.782‍ ‍—‍ ‍2.491， P<0.001）， positive HBeAg （OR=3.258， 95%CI： 2.629‍ ‍—‍ ‍4.038， P<0.001）， high HBV DNA level at baseline （OR=1.286， 95%CI： 1.157‍ ‍—‍ ‍1.430， P<0.001）， and history of entecavir treatment （OR=3.089， 95%CI： 1.880‍ ‍—‍ ‍5.074， P<0.001） were risk factors for LLV； duration of antiviral therapy ≥3 years （OR=0.175， 95%CI： 0.093‍ ‍—‍ ‍0.331， P<0.001） and high alanine aminotransferase level at baseline （OR=0.985， 95%CI： 0.978‍ ‍—‍ ‍0.992， P<0.001） were protective factors against LLV. The sensitivity analysis showed no significant change in effective value， suggesting that the results of the meta-analysis were relatively stable. The funnel plot of the studies included was basically symmetrical， and the results of the Egger’s test and the Begg’s test suggested that there was no obvious publication bias in the articles included. Conclusion Clinicians should guide decision making based on the influencing factors for LLV and related clinical evidence， so as to reduce long-term clinical risks and avoid adverse outcomes.
- Hepatitis B， Chronic /
- Low Level Viremia /
- Meta-Analysis

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图 1 文献筛选流程

Figure 1. Literature screening flowchart

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图 2 LLV发生率的Meta分析森林图

Figure 2. Forest plot of Meta-analysis of LLV incidence

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图 3 LLV发病率敏感性分析结果

Figure 3. Sensitivity analysis of the Meta-analysis of the incidence of LLV

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图 4 LLV发生率Meta分析的漏斗图

Figure 4. Meta-analysis funnel plot of LLV incidence

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图 5 HBeAg阳性Meta分析的漏斗图

Figure 5. Funnel plot of Meta-analysis of HBeAg positive

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表 1 纳入文献基本特征及质量评价结果

Table 1. Basic characteristics and quality evaluation results

纳入文献	年份	研究类型	研究地点	地理区域	LLV（例）	总样本量（例）	影响因素		质量评价
纳入文献	年份	研究类型	研究地点	地理区域	LLV（例）	总样本量（例）	危险	保护	评分	分级
张玉容^［15］	2021	横断面	福建	南方	35	86	①②	⑭	6	中
杨雪芳等^［16］	2023	横断面	云南	南方	55	121	①③④		6	中
宣碧碧等^［17］	2022	横断面	山东	北方	173	417	①	⑭⑮	9	高
李光海等^［18］	2023	横断面	海南	南方	101	322	①⑥⑦	⑬⑯	5	中
漆江红^［19］	2022	横断面	甘肃	北方	84	223	①③⑥		5	中
李彤等^［20］	2023	横断面	甘肃	北方	189	509	①③⑥⑧⑨	⑪⑫	7	中
黄永栩等^［21］	2023	横断面	广东	南方	40	260	①③⑦		7	中
程齐齐等^［22］	2022	横断面	江西	南方	20	78	③⑥	⑪	6	中
陈贺等^［23］	2021	横断面	江苏	南方	204	560	①③⑥		5	中
Lu等^［24］	2022	病例对照	广东	南方	139	278	①⑥		5	中
Li等^［25］	2023	队列	江苏	南方	90	394	①⑤⑩		7	高
Han等^［26］	2023	横断面	上海	南方	51	160	①⑧	⑭	7	中
注：①HBeAg阳性；②既往或目前使用非一线NAs类抗病毒药物；③基线HBV DNA水平高；④使用二线抗病毒药物；⑤HBV DNA水平≥1.0×10⁸ IU/mL；⑥HBsAg定量高；⑦治疗期间依从性差；⑧ETV治疗史；⑨高HBeAg水平；⑩抗-HBc水平<3 log₁₀ IU/mL；⑪基线ALT水平高；⑫治疗中HBV DNA水平下降幅度大；⑬治疗期间依从性好；⑭抗病毒治疗时间≥3年；⑮2年≤抗病毒治疗时间<3年；⑯基线HBV DNA水平低。

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表 2 亚组分析结果

Table 2. Subgroup analysis results

地理区域	文献篇数	异质性检验		效应模型	效应量（95%CI）	P值
地理区域	文献篇数	I²值	P值	效应模型	效应量（95%CI）	P值
北方	3^{［17，19-20］}	0%	0.374	固定	38.8%（36.0%～41.6%）	<0.001
南方	8^{［15-16，18，21-23，25-26］}	90.11%	<0.001	随机	28.4%（26.4%～30.3%）

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表 3 影响因素的Meta分析结果

Table 3. Results of meta-analysis of influencing factors

影响因素	文献篇数	异质性		效应模型	合并效应量		P值
影响因素	文献篇数	I²值	P值	效应模型	OR（95%CI）	Z值	P值
HBeAg阳性	11^{［15-21，23-26］}	0%	0.600	固定	3.258（2.629～4.038）	10.790	<0.001
基线HBV DNA水平高	6^{［16，19-23］}	20.3%	0.285	固定	1.286（1.157～1.430）	4.656	<0.001
HBsAg定量高	6^{［18-20，22-24］}	36.3%	0.165	固定	2.107（1.782～2.491）	8.728	<0.001
ETV治疗史	2^{［20，26］}	10.2%	0.291	固定	3.089（1.880～5.074）	4.453	<0.001
基线ALT水平高	2^{［20，22］}	48.2%	0.165	固定	0.985（0.978～0.992）	-4.337	<0.001
抗病毒治疗时间≥3年	3^{［15，17，26］}	0%	0.966	固定	0.175（0.093～0.331）	-5.378	<0.001

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