[1]吕承秀a,c,陈 梅b,等.慢性乙型肝炎患者接受核苷（酸）类似物治疗后发生低病毒血症的危险因素及机制研究[J].现代检验医学杂志,2023,38(05):133-137+184.[doi:10.3969/j.issn.1671-7414.2023.05.025]
　L? Chengxiua,c,CHEN Meib,et al.Risk Factors and Mechanism of Low-level Viremia in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogues Treatment[J].Journal of Modern Laboratory Medicine,2023,38(05):133-137+184.[doi:10.3969/j.issn.1671-7414.2023.05.025]
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慢性乙型肝炎患者接受核苷（酸）类似物治疗后发生低病毒血症的危险因素及机制研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年05期
页码:
133-137+184
栏目:
论著
出版日期:
2023-09-15

文章信息/Info

Title:
Risk Factors and Mechanism of Low-level Viremia in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogues Treatment
文章编号:
1671-7414（2023）05-133-06
作者:
吕承秀a; c; 陈 梅b; 王纪传b; 李 庆a; c; 张琨婷a; c; 孙晓琳a; c
（淄博市第一医院 a. 检验科；b. 感染性疾病科；c. 分子免疫检验医学重点实验室，山东淄博 255200）
Author(s):
L? Chengxiua; c; CHEN Meib; WANG Jichuanb; LI Qinga; c; ZHANG Kuntinga; c; SUN Xiaolina; c
（a.Department of Clinical Laboratory；b. Department of Infection Diseases；c. Key Laboratory of Molecular Immunology of Laboratory Medicine, Zibo First Hospital, Shangdong Zibo 255200，China）
关键词:
慢性乙型肝炎; 低病毒血症; 双链松弛环状脱氧核糖核酸; 前基因组核糖核酸
分类号:
R512.62；R446
DOI:
10.3969/j.issn.1671-7414.2023.05.025
文献标志码:
A
摘要:
目的 研究慢性乙型肝炎(chronic hepatitis B，CHB) 患者接受核苷（酸）类似物[nucleos(t)ide analogues，NAs]治疗下发生低病毒血症(low-level viremia，LLV) 的危险因素及机制。方法 选取2021 年5 月～ 2023 年3 月淄博市第一医院感染科门诊就诊的NAs 治疗疗程大于48 周且高敏HBV DNA<2 000IU/ml 的115 例CHB 患者，根据高敏HBVDNA 定量结果分为持续性LLV 组（n=34）、间歇性LLV 组（n=32）及持续病毒学应答(sustained virologic response，SVR) 组（n=49）；收集患者NAs 治疗前临床特征及实验室指标进行组间比较，采用Logistic 回归分析确定LLV 发生的危险因素；抽取患者NAs 治疗后血清进行肝功能指标、乙型肝炎病毒双链松弛环状DNA(hepatitis B virus doublestrandrelaxed circular DNA，HBV rcDNA) 及前基因组RNA (pregenomic RNA，pgRNA) 检测并进行结果的组间比较，探讨LLV 发生的机制。结果 持续性LLV 组、间歇性LLV 组及SVR 组乙型肝炎e 抗原（hepatitis B e antigen，HBeAg）阳性率分别为70.59%，53.13% 和10.20%，乙型肝炎表面抗原（hepatitis B surface antigen，HBsAg）(lgIU/ml) 结果分别为3.27(3.03，3.61), 3.04(2.93，3.26) 和 2.99(2.20，3.16)。间歇性LLV 组和持续性LLV 组HBeAg 阳性率均高于SVR 组（χ2=14.005，27.192，均P<0.001），持续性LLV 组HBsAg 结果高于SVR 组(Z=-3.375，P=0.001)，差异均有统计学意义( 均P<0.05)。Logistic 回归分析发现，患者治疗前HBeAg 阳性（OR:8.660，95%CI:2.865 ～ 26.183）是患者发生LLV 的独立危险因素。持续性LLV 组、间歇性LLV 组及SVR 组HBV rcDNA 的阳性率分别为58.82%，6.25% 和0.00%，pgRNA 阳性率分别为52.94%，18.75% 和4.08%。持续性LLV 组HBV rcDNA 阳性率高于SVR 组和间歇性LLV 组（χ2=20.504，37.974，均P<0.001），持续性LLV 组pgRNA 阳性率高于间歇性LLV 组和SVR 组（χ2=8.328, 26.199；P=0.005, <0.001），差异均有统计学意义。结论 CHB 患者NAs 治疗前HBeAg 阳性是发生LLV 的独立危险因素；NAs 治疗后部分LLV 患者HBV pgRNA 阳性且定量水平高，HBV rcDNA 维持在较高的合成水平，NAs 无法完成抑制rcDNA 的合成，从而导致LLV 的发生。
Abstract:
Objective To investigate the risk factors and mechanism of low-level viremia (LLV) in patients with chronic hepatitis B (CHB) who receive nucleos(t)ide analogues (NAs) treatment. Methods 115 CHB patients who received NAs treatment for more than 48 weeks and had HBV DNA<2 000IU/ml were selected from the Department of Infection Diseases of Zibo First Hospital from May 2021 to March 2023. Based on the results of high sensitivity HBV DNA quantification, patients were divided into persistent LLV group （n=34）, intermittent LLV group（n=32）, and sustained virologic response (SVR) group（n=49）. Clinical characteristics and laboratory indicators of patients with NAs before treatment were collected for inter group comparison. Logistic regression analysis was used to determine the risk factors for LLV occurrence. The serum of patients under NAs treatment was extracted for liver function indicators, hepatitis B virus double-stranded relaxed circular DNA (HBV rcDNA) and pregenomic RNA (pgRNA) detection. The results were compared between groups to explore the mechanism of LLV occurrence.Results The HBeAg positive rates in the persistent LLV group，intermittent LLV group，and SVR group were 70.59%， 53.13% and 10.20%，respectively. The HBsAg (lgIU/ml) results were 3.27 (3.03，3.61)，3.04 (2.93，3.26) and 2.99 (2.20，3.16)， respectively. The HBeAg positive rates in the intermittent LLV group and the persistent LLV group were higher than those in the SVR group（χ2=14.005，27.192，all P<0.001）, and the HBsAg values in the persistent LLV group were higher than those in the SVR group(Z=-3.375，P=0.001) with statistical significance. Logistic regression analysis found that HBeAg positivity(OR: 8.660, 95%CI: 2.865~26.183) before treatment was an independent risk factor for the development of LLV in patients. The positive rates of HBV rcDNA in the persistent LLV group, intermittent LLV group, and SVR group were 58.82%, 6.25% and 0.00%, respectively. The positive rates of pgRNA were 52.94%, 18.75% and 4.08%, respectively. The positive rate of HBV rcDNA in the persistent LLV group was higher than that in the SVR group and intermittent LLV group（χ2=20.504，37.974，all P<0.001)， the positive rate of pgRNA in the persistent LLV group was higher than that in the intermittent LLV group and SVR group （χ2=8.328，26.199；P=0.005，<0.001), the differences were statistically significant. Conclusion HBeAg positivity before NAs treatment in CHB patients is an independent risk factor for the development of LLV. Some patients under treatment with NAs with LLV had positive HBV pgRNA and high quantitative levels, the synthesis of HBV rcDNA was high level, NAs can not complete the inhibition of rcDNA synthesis, leading to the occurrence of LLV.

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备注/Memo

备注/Memo:
基金项目： 淄博市第一医院院级课题（2022YJKT-28）：CHB 患者低病毒血症与rcDNA 及pgRNA 的相关性研究。
作者简介：吕承秀(1987-），男，硕士，主管检验师，研究方向：病原体分子生物学检验， E-mail: lvchengxiu870901@126.com。
通讯作者：孙晓琳(1982-)，女，硕士，副主任技师，研究方向：病原微生物学， E-mail: zb ＿ lab@163.com。
更新日期/Last Update: 2023-09-15