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
Incidence rate of low-level viremia and related influencing factors in treatment-experienced chronic hepatitis B patients: A Meta-analysis
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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。 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. -
Key words:
- Hepatitis B, Chronic /
- Low Level Viremia /
- Meta-Analysis
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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 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。 表 2 亚组分析结果
Table 2. Subgroup analysis results
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 I2值 P值 OR(95%CI) Z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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