慢性乙型肝炎患者血清HBV RNA水平与核苷（酸）类似物治疗时间的关系

范雪莉; 詹爱琴; 安轶; 田丽艳

doi:10.12449/JCH240111

慢性乙型肝炎患者血清HBV RNA水平与核苷（酸）类似物治疗时间的关系

DOI: 10.12449/JCH240111

范雪莉¹,
詹爱琴^2, , ,,
安轶³,
田丽艳¹

1.
石河子大学医学院，新疆石河子 832000
2.
石河子大学医学院第一附属医院感染科，新疆石河子 832000
3.
中国医科大学第一临床学院，沈阳 110001

基金项目:

中国肝炎防治基金会天晴肝病研究基金 (TQGB20170175)

伦理学声明：本研究方案于2023年1月28日经由石河子大学医学院第一附属医院伦理委员会审批，批号为KJX2022-074-01。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：范雪莉负责收集数据，资料分析，撰写论文，拟定写作思路及修改论文；詹爱琴参与修改论文及最后定稿；安轶、田丽艳负责收集数据，资料分析。

详细信息

通信作者:
詹爱琴， zhanaiqin@126.com （ORCID： 0000-0002-5436-1974）

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出版历程
- 收稿日期: 2023-02-20
- 录用日期: 2023-04-07
- 出版日期: 2024-01-23

Correlation between serum HBV RNA and duration of treatment with nucleos（t）ide analogues in patients with chronic hepatitis B

Xueli FAN¹,
Aiqin ZHAN^{2
, ,
,},
Yi AN³,
Liyan TIAN¹

1.
Shihezi University School of Medicine，Shihezi，Xinjiang 832000，China
2.
Department of Infectious Diseases，The First Affiliated Hospital of Shihezi University School of Medicine，Shihezi，Xinjiang 832000，China
3.
The First Clinical College of China Medical University，Shenyang 110001，China

Research funding:

‍Tianqing Liver Disease Research Foundation of China Hepatitis Prevention and Treatment Foundation (TQGB20170175)

More Information

Corresponding author: ZHAN Aiqin， zhanaiqin@126.com （ORCID： 0000-0002-5436-1974）

摘要

摘要: 目的检测未治疗和经过治疗的慢性乙型肝炎（CHB）患者血清HBV RNA水平，并分析血清HBV RNA水平与核苷（酸）类似物（NAs）抗病毒治疗时间的关系。方法选取2022年2月—2022年7月间就诊于石河子大学医学院第一附属医院感染科门诊患者中的300例CHB患者为研究对象。收集患者临床资料，根据患者抗病毒治疗时间不同分为未治疗组（n=73）、治疗时间≤1年组（n=91）、治疗时间>1年组（n=136），检测患者血清HBV RNA和HBV DNA载量及HBsAg浓度。计量资料两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Bonferroni校正法；计数资料用χ²检验，采用Spearman相关分析比较各指标间相关程度。结果 HBeAg阳性率18.3%，在HBV DNA阴性者中HBV RNA阳性者占比44.1%（86/195）。HBeAg阳性组和HBeAg阴性组患者血清HBV RNA、HBV DNA、HBsAg水平分布差异均具有统计学意义（Z值分别为10.740、6.300、7.280，P值均<0.05）。未治疗组与治疗时间≤1年组仅有DNA水平分布情况有统计学差异（P<0.05），未治疗组与治疗时间>1年组HBV RNA、HBV DNA水平分布差异均有统计学意义（P值均<0.05），治疗时间≤1年与治疗时间>1年组中HBV RNA、HBV DNA、HBsAg水平分布情况差异均有统计学意义（P值均<0.05）。抗病毒治疗时间与HBV RNA、HBsAg水平呈极弱负相关（r值分别为-0.247、-0.138，P值均<0.05），与HBV DNA水平呈强负相关（r=-0.771，P<0.001）。血清HBV RNA与HBV DNA、HBsAg水平呈低度相关（r值分别为0.360、0.442，P值均<0.001），进一步分层分析显示，在未治疗组中，HBV RNA与HBV DNA水平呈强正相关（r=0.752，P<0.001），与HBsAg水平呈中度正相关（r=0.559，P<0.001）；在治疗时间≤1年组中，HBV RNA与HBV DNA、HBsAg水平呈低度正相关（r值分别为0.396、0.388，P值均<0.001）；在治疗时间>1年组中，HBV RNA与HBsAg水平呈低度正相关（r=0.352，P<0.001）。结论血清HBV RNA与NAs治疗时间呈负相关，与HBV DNA、HBsAg水平的相关性随着治疗时间的延长逐渐下降，可以在一定程度上作为CHB患者病毒学水平监测的补充指标，尤其在未治疗患者中反映病毒复制水平准确性较高。
- 乙型肝炎，慢性 /
- 核苷类 /
- 核苷酸类
Abstract: ‍ Objective To investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B （CHB） and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos（t）ide analogues （NAs）. Methods A total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July， 2022， were enrolled as subjects. Related clinical data were collected， and according to the duration of antiviral therapy， they were divided into untreated group with 73 patients， treatment duration ≤1 year group with 91 patients， and treatment duration >1 year group with 136 patients. Serum HBV RNA load， HBV DNA load， and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups， further pairwise comparison using Bonferroni method； the chi-square test was used for comparison of categorical data； a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. Results The positive rate of HBeAg was 18.3%， and among the patients with negative HBV DNA， the patients with positive HBV RNA accounted for 44.1% （86/195）. There was a significant difference in the distribution of the serum levels of HBV RNA， HBV DNA， and HBsAg between the positive HBeAg group and the negative HBeAg group （Z=10.740， 6.300， and 7.280， all P<0.05）. There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA， HBV DNA， and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group （P<0.05）. The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA， HBV DNA， and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg （r=-0.247 and -0.138， both P<0.05） and a strong negative correlation with the level of HBV DNA （r=-0.771， P<0.001）. There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg （r=0.360 and 0.442， both P<0.001）. Further stratified analysis showed that in the untreated group， there was a strong positive correlation between HBV RNA and HBV DNA （r=0.752， P<0.001） and a moderate positive correlation between HBV RNA and HBsAg （r=0.559， P<0.001）； in the treatment duration ≤1 year group， there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg （r=0.396 and r=0.388， both P<0.001）； in the treatment duration >1 year group， there was a low degree of positive correlation between HBV RNA and HBsAg （r=0.352， P<0.001）. Conclusion Serum HBV RNA is negatively correlated with the duration of treatment with NAs， and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore， it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent， with a relatively high accuracy in reflecting the level of viral replication in untreated patients.
- Hepatitis B， Chronic /
- Nucleosides /
- Nucleotides

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图 1 HBV RNA与HBV DNA、HBsAg的相关性

Figure 1. Correlation of HBV RNA with HBV DNA and HBsAg

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表 1 一般资料比较

Table 1. Comparison of general data

指标	HBeAg阳性组（n=55）	HBeAg阴性组（n=245）	统计值	P值
年龄（岁）	46（35～53）	51（45～56）	Z=-3.116	0.002
性别［例（%）］			χ²=0.615	0.433
男	34（61.8）	165（67.3）
女	21（38.2）	80（32.7）
HBV RNA（lg 拷贝/mL）	6.02（4.50～7.33）	2.00（2.00～2.75）	Z=10.831	<0.001
HBV DNA（lg IU/mL）	3.58（2.00～6.48）	2.00（2.00～2.75）	Z=6.298	<0.001
HBsAg（lg IU/mL）	3.64（3.19～4.28）	2.77（2.09～3.21）	Z=7.282	<0.001
ALT（U/L）	24.60（16.40～53.40）	19.80（14.60～26.30）	Z=3.563	<0.001
AST（U/L）	24.60（20.20～33.90）	19.90（16.95～24.55）	Z=3.703	<0.001

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表 2 不同的抗病毒药物对各指标的影响

Table 2. Effects of different antiviral drugs on various indicators

指标	恩替卡韦组（n=180）	替诺福韦组（n=46）	统计值	P值
HBV DNA检出率［例（%）］	28（15.6）	4（8.7）	χ²=1.418	0.234
HBV RNA检出率［例（%）］	85（47.2）	23（50.0）	χ²=0.113	0.736
HBV DNA（lg IU/mL）	2.00（2.00～2.00）	2.00（2.00～2.00）	Z=-1.334	0.182
HBV RNA（lg 拷贝/mL）	2.00（2.00～3.20）	2.09（2.00～4.20）	Z=0.861	0.389
HBsAg（lg IU/mL）	2.88（2.28～3.38）	2.92（2.50～3.57）	Z=0.539	0.590

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表 3 抗病毒治疗时间不同HBV RNA、HBV DNA、HBsAg水平差异

Table 3. Differences in HBV RNA， HBV DNA， and HBsAg levels at different times of antiviral treatment

组别	例数	HBV RNA（lg 拷贝/mL）	HBV DNA（lg IU/mL）	HBsAg（lg IU/mL）
未治疗组	73	2.73（2.00～5.11）	3.96（3.33～6.00）	2.86（2.11～3.70）
治疗时间≤1年组	91	2.47（2.00～4.71）	2.00（2.00～2.71）^1）	3.25（2.63～3.84）
治疗时间>1年组	136	2.00（2.00～2.94）^1）2）	2.00（2.00～2.00）^1）2）	2.78（2.20～3.13）^2）
H值		19.301	206.390	13.693
P值		<0.001	<0.001	0.001
注：与未治疗组比较，1）P<0.05；与治疗时间≤1年组比较，2）P<0.05。

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