血清HBV RNA在HBeAg阳性慢性乙型肝炎患者不同时期的表达水平及检测价值

王成康; 刘寿荣

doi:10.3969/j.issn.1001-5256.2021.12.014

血清HBV RNA在HBeAg阳性慢性乙型肝炎患者不同时期的表达水平及检测价值

DOI: 10.3969/j.issn.1001-5256.2021.12.014

王成康¹,
刘寿荣^2, ,

1.
浙江大学医学院附属第四医院感染科，浙江义乌 322000
2.
杭州市西溪医院肝病科，杭州 310023

基金项目:

杭州市科技局计划项目 (20191203B116)

详细信息

通信作者:
刘寿荣，lsr85463990@sina.com

中图分类号: R512.62
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出版历程
- 收稿日期: 2021-04-21
- 录用日期: 2021-05-10
- 出版日期: 2021-12-20

Expression level of serum HBV RNA in HBeAg-positive chronic hepatitis B patients at different periods and its value of measurement

Chengkang WANG¹,
Shourong LIU^{2
, ,}

1.
Department of Infectious Diseases, The Fourth Affiliated Hospital ZheJiang University School of Medicine, YiWu, ZheJiang 322000, China
2.
Department of Hepatology, Hangzhou Xixi Hospital, Hangzhou 310023, China

Research funding:

Hangzhou Science and Technology Bureau Plan Project (20191203B116)

摘要

摘要: 目的探讨血清HBV RNA在HBeAg阳性慢性乙型肝炎(CHB)患者不同时期的表达水平及潜在临床价值。方法选取2019年8月—2020年12月于杭州市西溪医院肝病科门诊及住院部就诊的CHB患者61例，根据HBeAg阳性CHB患者的抗病毒治疗情况分为3组：HBeAg阳性CHB[HBeAg(+)、HBV DNA(+)]未治患者(A组)，HBeAg血清学转换前[HBeAg(+)、HBV DNA(-)]经治患者(B组)，HBeAg血清学转换后[HBeAg(-)、HBV DNA(-)]经治患者(C组)，检测不同时期患者外周血HBV RNA载量，并分析其与HBsAg、HBV D NA的相关性。符合正态分布的计量资料2组间比较采用t检验；非正态分布的计量资料2组间比较采用Mann-Whitney U检验；计数资料2组间比较采用χ²检验；采用Pearson或Spearman相关分析描述两变量间的相关性。结果 3组患者HBV RNA阳性率分别为100%(22/22)、88.2%(15/17)、22.7%(6/22)。HBeAg阳性CHB未治患者HBV RNA与HBsAg、HBV DNA均呈正相关(r值分别为0.612、0.922，P值均＜0.01)，在HBeAg血清学转换前和HBeAg血清学转换后的经治患者中，HBV RNA与HBsAg无相关性。经治HBeAg阳性组的HBV RNA、HBsAg均高于HBeAg阴性组，差异均有统计学意义(Z值分别为-4.44、-2.41，P值均＜0.05)。HBV DNA阳性组HBV RNA显著高于HBV DNA阴性组，差异有统计学意义(Z=-6.16, P＜0.01)。结论 CHB患者经核苷(酸)类药物抗病毒治疗HBV DNA阴转后仍有部分患者能检测出血清HBV RNA；且HBV RNA只能来自肝内cccDNA, 因此HBV RNA比HBV DNA更能反映肝内病毒复制活性，对CHB人群管理有着一定的临床价值。
- 乙型肝炎, 慢性 /
- 乙型肝炎病毒 /
- RNA, 病毒 /
- DNA, 病毒 /
- 乙型肝炎e抗原
Abstract: Objective To investigate the expression level and potential clinical value of serum HBV RNA in HBeAg-positive chronic hepatitis B (CHB) patients at different periods. Methods A total of 61 CHB patients who attended the outpatient and inpatient services of Department of Hepatology, Hangzhou Xixi Hospital, from August 2019 to December 2020 were enrolled, and according to the antiviral therapy for HBeAg-positive CHB patients, they can be divided into group A with untreated HBeAg-positive CHB (HBeAg+ and HBV DNA+) patients, group B with treatment-experienced patients before HBeAg seroconversion (HBeAg+ and HBV DNA-), and group C with treatment-experienced patients after HBeAg seroconversion (HBeAg- and HBV DNA-). Peripheral blood HBV RNA load was measured at different periods, and its correlation with HBsAg and HBV DNA was analyzed. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups; a Pearson or Spearman correlation analysis was used to describe the correlation between two variables. Results The positive rates of HBV RNA in these three groups were 100% (22/22), 88.2% (15/17), and 22.7% (6/22), respectively. In group A, HBV RNA was positively correlated with HBsAg and HBV DNA (r=0.612 and 0.922, both P < 0.01), while in groups B and C, there was no correlation between HBV RNA and HBsAg. Group B had significantly higher levels of HBV RNA and HBsAg than group C (Z=-4.44 and -2.41, both P < 0.05). The HBV DNA-positive group had a significantly higher level of HBV RNA than the HBV DNA-negative group (Z=-6.16, P < 0.01). Conclusion After HBV DNA clearance achieved by antiviral therapy with nucleos(t)ide analogues in CHB patients, serum HBV RNA can still be detected in some of these patients. Since HBV RNA only comes from cccDNA in the liver, it can better reflect viral replication activity in the liver than HBV DNA and thus has a certain clinical value in the management of CHB patients.
- Hepatitis B, Chronic /
- Hepatitis B virus /
- RNA, Viral /
- DNA, Viral /
- Hepatitis B e Antigens

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图 1 HBeAg阳性CHB未治患者HBV RNA与HBsAg、HBV DNA的相关性

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表 1 纳入患者分组情况及基线资料

组别	例数	男	女	年龄(岁)
HBeAg(+)、HBV DNA(+)	22	13	9	35.36±7.55
HBeAg(+)、HBV DNA(-)	17	11	6	39.35±7.98
HBeAg(-)、HBV DNA(-)	22	13	9	45.00±11.16

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表 2 经治患者HBeAg阳性组与HBeAg阴性组临床资料比较

项目	HBeAg阳性组(n=17)	HBeAg阴性组(n=22)	统计值	P值
男/女(例)	11/6	13/9		0.753
年龄(岁)	39.35±7.98	45.00±11.16	t=-1.77	0.086
HBV RNA阳性[例(%)]	15(88.2)	6(27.3)		＜0.001
HBV RNA(log₁₀拷贝/mL)	4.05(3.01~5.18)	1.40(1.40~1.83)	Z=-4.44	＜0.001
HBsAg(log₁₀IU/mL)	3.24(2.86~3.50)	2.76(2.07~3.35)	Z=-2.41	0.016
ALT(U/L)	22.24±10.83	25.09±11.76	t=-0.78	0.442
AST(U/L)	23.00±4.48	23.9±14.23	t=-0.65	0.521

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表 3 HBV DNA阳性组与HBV DNA阴性组临床资料比较

项目	HBV DNA阳性组(n=22)	HBV DNA阴性组(n=39)	统计值	P值
男/女(例)	13/9	24/15	χ²=0.035	0.851
年龄(岁)	35.36±7.55	42.54±10.18	t=-2.88	0.005
HBV RNA(log₁₀拷贝/mL)	7.62(6.51~8.55)	1.94(1.40~4.04)	Z=-6.16	＜0.001
HBsAg(log₁₀IU/mL)	3.94(3.26~4.23)	2.90(2.61~3.44)	Z=-4.07	＜0.001
ALT(U/L)	249.50(114.25~664.50)	20.00(16.00~31.00)	Z=-6.45	＜0.001
AST(U/L)	106.00(63.75~418.75)	23.00(21.00~27.00)	Z=-6.45	＜0.001
HBV DNA(log₁₀IU/ml)	7.21±1.23	-

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