HBV相关慢加急性肝衰竭恢复期患者肝组织HBV cccDNA水平及其临床意义

蔡哲凯, 徐龙, 刘文丽, 肖影群, 钟青梅, 张伟, 吴敏

PDF(671 KB)
中国高校科技期刊信息汇聚平台
PDF(671 KB)
临床肝胆病杂志 ›› 2025, Vol. 41 ›› Issue (1) : 57-62. DOI: 10.12449/JCH250109
病毒性肝炎

HBV相关慢加急性肝衰竭恢复期患者肝组织HBV cccDNA水平及其临床意义

作者信息 +

The level of HBV cccDNA in liver tissue and its clinical significance in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure

Author information +
History +

摘要

目的 观察HBV cccDNA在HBV相关慢加急性肝衰竭（HBV-ACLF）恢复期患者肝组织中的表达水平，并探讨其与HBV标志物、肝组织病理改变的关系。 方法 选取2015年1月—2023年10月在南昌市第九医院住院的HBV-ACLF恢复期患者30例为肝衰竭组，另选取同期9例性别及年龄匹配的慢性乙型肝炎患者（CHB）作为对照组，检测肝组织HBV cccDNA水平，并分析其与临床资料、实验室检查指标的关联性。计量资料两组间比较采用成组t检验或Mann-Whitney U检验；多组间比较采用单因素方差分析或Kruskal-Wallis H检验。计数资料组间比较采用Fisher精确检验。相关性分析采用Spearman相关分析。 结果 肝衰竭组肝组织HBV cccDNA水平显著低于对照组［（-0.92±0.70） log10 copies/cell vs （-0.13±0.91） log10 copies/cell，t=2.761，P=0.009］。肝衰竭组中，血清HBeAg阳性与阴性患者肝组织HBV cccDNA水平比较，差异无统计学意义（P>0.05）；肝组织炎症活动度G0～G2级、G3级、G4级患者的肝组织HBV cccDNA水平比较，差异无统计学意义（P>0.05）；肝组织纤维化程度S0～S2期、S3期、S4期患者的肝组织HBV cccDNA水平比较，差异无统计学意义（P>0.05）；血清HBV DNA阴性与血清HBV DNA阳性患者肝组织HBV cccDNA水平比较，差异无统计学意义（P>0.05）。肝衰竭组肝组织HBV cccDNA水平与肝组织HBV DNA水平呈正相关（r=0.426，P=0.043），与血清HBV DNA水平无明显相关性（P>0.05）。 结论 肝组织HBV cccDNA水平在HBV-ACLF恢复期明显降低，肝组织HBV cccDNA持续稳定存在，较血清及肝组织HBV DNA更能反映HBV的持续感染与复制。

Abstract

Objective To investigate the expression level of HBV cccDNA in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） and its correlation with HBV markers and liver histopathological changes. Methods A total of 30 patients in the convalescence stage of HBV-ACL who were hospitalized in The Ninth Hospital of Nanchang from January 2015 to October 2023 were enrolled as liver failure group， and 9 patients with chronic hepatitis B （CHB）， matched for sex and age， were enrolled as control group. The content of HBV cccDNA in liver tissue was measured， and its correlation with clinical data and laboratory markers was analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and a one-way analysis of variance or the Kruskal-Wallis H test was used for comparison between multiple groups； the Fisher’s exact test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed. Results The liver failure group had a significantly lower content of HBV cccDNA in liver tissue than the control group （-0.92±0.70 log10 copies/cell vs -0.13±0.91 log10 copies/cell， t=2.761， P=0.009）. In the liver failure group， there was no significant difference in the content of HBV cccDNA in liver tissue between the HBeAg-positive patients and the HBeAg-negative patients （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different grades （G0-G2， G3， and G4） of liver inflammatory activity （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different stages （S0-S2， S3， and S4） of liver fibrosis （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with negative HBV DNA and those with positive HBV DNA （P>0.05）. For the liver failure group， the content of HBV cccDNA in liver tissue was positively correlated with the content of HBV DNA in liver tissue （r=0.426， P=0.043） and was not significantly correlated with the content of HBV DNA in serum （P>0.05）. Conclusion There is a significant reduction in the content of HBV cccDNA in liver tissue in the convalescence stage of HBV-ACLF. HBV cccDNA exists continuously and stably in liver tissue and can better reflect the persistent infection and replication of HBV than HBV DNA in serum and liver tissue.

关键词

乙型肝炎病毒 / 慢加急性肝功能衰竭 / 恢复期 / 共价闭合环状DNA

Key words

Hepatitis B Virus / Acute-On-Chronic Liver Failure / Convalescence / Covalently Closed Circular DNA

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
蔡哲凯 , 徐龙 , 刘文丽 , 等. HBV相关慢加急性肝衰竭恢复期患者肝组织HBV cccDNA水平及其临床意义. 临床肝胆病杂志. 2025, 41(1): 57-62 https://doi.org/10.12449/JCH250109
Zhekai CAI, Long XU, Wenli LIU, et al. The level of HBV cccDNA in liver tissue and its clinical significance in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure[J]. Journal of Clinical Hepatol. 2025, 41(1): 57-62 https://doi.org/10.12449/JCH250109

参考文献

列表( 原文顺序 | 文献年度倒序 | 文中引用次数倒序 ) 可视化分析
1
MOREAU R, GAO B, PAPP M, et al. Acute-on-chronic liver failure: A distinct clinical syndrome[J]. J Hepatol, 2021, 75(): S27-S35. DOI: 10.1016/j.jhep.2020.11.047 .
本文引用 [1] 摘要
Suppl 1
2
Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007 .
中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007 .
本文引用 [2]
3
SARIN SK, CHOUDHURY A, SHARMA MK, et al. Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL): An update[J]. Hepatol Int, 2019, 13(4): 353-390. DOI: 10.1007/s12072-019-09946-3 .
本文引用 [1]
4
ZHANG B, DILIHUMAER ZYE, ZHANG SY, et al. Progress on pathogenesis and medical treatment of hepatitis B virus-related chronic and acute liver failure[J/CD]. Chin J Liver Dis (Electronic Version), 2023, 15(1): 28-33. DOI: 10.3969/j.issn.1674-7380.2023.01.005 .
张斌, 迪丽胡玛尔·扎依尔, 张诗雨, 等. 乙型肝炎相关慢加急性肝衰竭发病机制及治疗进展[J/CD]. 中国肝脏病杂志(电子版), 2023, 15(1): 28-33. DOI: 10.3969/j.issn.1674-7380.2023.01.005 .
本文引用 [1]
5
GU WY, XU BY, ZHENG X, et al. Acute-on-chronic liver failure in China: Rationale for developing a patient registry and baseline characteristics[J]. Am J Epidemiol, 2018, 187(9): 1829-1839. DOI: 10.1093/aje/kwy083 .
本文引用 [1]
6
WURSTHORN K, LUTGEHETMANN M, DANDRI M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B[J]. Hepatology, 2006, 44(3): 675-684. DOI: 10.1002/hep.21282 .
本文引用 [1]
7
Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B[J]. Infect Dis Inf, 2023, 36(1): 1-17. DOI: 10.3969/j.issn.1007-8134.2023.01.01 .
中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 传染病信息, 2023, 36(1): 1-17. DOI: 10.3969/j.issn.1007-8134.2023.01.01 .
本文引用 [1]
8
VERRIER ER, COLPITTS CC, BACH C, et al. A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses[J]. Hepatology, 2016, 63(1): 35-48. DOI: 10.1002/hep.28013 .
本文引用 [1]
9
TSUKUDA S, WATASHI K. Hepatitis B virus biology and life cycle[J]. Antiviral Res, 2020, 182: 104925. DOI: 10.1016/j.antiviral.2020.104925 .
本文引用 [1]
10
MACOVEI A, PETRAREANU C, LAZAR C, et al. Regulation of hepatitis B virus infection by Rab5, Rab7, and the endolysosomal compartment[J]. J Virol, 2013, 87(11): 6415-6427. DOI: 10.1128/JVI.00393-13 .
本文引用 [1]
11
XIA YC, GUO HT. Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential[J]. Antiviral Res, 2020, 180: 104824. DOI: 10.1016/j.antiviral.2020.104824 .
本文引用 [2]
12
YAN Y, ALLWEISS L, YANG DL, et al. Down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes prevents hepatitis B virus infection[J]. Emerg Microbes Infect, 2019, 8(1): 879-894. DOI: 10.1080/22221751.2019.1625728 .
本文引用 [1]
13
LUTGEHETMANN M, VOLZ T, KÖPKE A, et al. In vivo proliferation of hepadnavirus-infected hepatocytes induces loss of covalently closed circular DNA in mice[J]. Hepatology, 2010, 52(1): 16-24. DOI: 10.1002/hep.23611 .
本文引用 [1]
14
ALLWEISS L, VOLZ T, GIERSCH K, et al. Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo[J]. Gut, 2018, 67(3): 542-552. DOI: 10.1136/gutjnl-2016-312162 .
本文引用 [1]
15
WEN B, YUAN J, LI XH, et al. The clinical features in chronic severe hepatiti B patients with HBeAg-positive and HBeAg-negative[J]. Chin J Prim Med Pharm, 2010, 17(1): 50-52. DOI: 10.3760/cma.j.issn.1008-6706.2010.01.024 .
文彬, 袁静, 李晓鹤, 等. HBeAg阳性与HBeAg阴性慢性重型乙型肝炎死亡患者的临床特征比较[J]. 中国基层医药, 2010, 17(1): 50-52. DOI: 10.3760/cma.j.issn.1008-6706.2010.01.024 .
本文引用 [1]
16
RAO M, LU W, ZHANG ZQ, et al. The relationship among HBV cccDNA, HBV total DNA in liver tissue and serum HBV DNA and their clinic-pathological significances in patients with chronic hepatitis B[J]. Chin Hepatol, 2012, 17(6): 381-384. DOI: 10.14000/j.cnki.issn.1008-1704.2012.06.013 .
饶敏, 陆伟, 张占卿, 等. 慢性乙型肝炎患者肝组织HBV cccDNA、总HBV DNA与血清HBV DNA的相关性及其与临床的关系[J]. 肝脏, 2012, 17(6): 381-384. DOI: 10.14000/j.cnki.issn.1008-1704.2012.06.013 .
本文引用 [2]
17
XIE YL, HUANG WL, DU J, et al. The relationship between HBV cccDNA of chronic hepatitis B patients liver tissues andserum HBsAg and liverinjury[J]. China J Mod Med, 2014, 24(22): 25-27.
谢元林, 黄维亮, 杜杰, 等. 乙肝患者肝组织cccDNA与血清HBsAg及肝损伤的关系[J]. 中国现代医学杂志, 2014, 24(22): 25-27.
本文引用 [1]
18
LIU XY, CHEN J, XIAO L, et al. Clinical features of HBV-associated acute-on-chronic liver failure induced by discontinuation of nucleoside analogues[J]. J Clin Hepatol, 2016, 32(9): 1766-1769. DOI: 10.3969/j.issn.1001-5256.2016.09.028 .
刘晓燕, 陈婧, 肖珑, 等. 停用核苷和核苷酸类药物诱发HBV相关慢加急性肝衰竭患者的临床特点分析[J]. 临床肝胆病杂志, 2016, 32(9): 1766-1769. DOI: 10.3969/j.issn.1001-5256.2016.09.028 .
本文引用 [1]
19
ZHANG X, LU W, ZHENG Y, et al. In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection[J]. J Clin Invest, 2016, 126(3): 1079-1092. DOI: 10.1172/JCI83339 .
本文引用 [1]
20
CHEN JL, YUAN ZH. Influence of interferon and nucleos (t) ide analogues on HBV cccDNA and functional cure of chronic hepatitis B[J]. J Clin Hepatol, 2019, 35(6): 1181-1187. DOI: 10.3969/j.issn.1001-5256.2019.06.002 .
陈捷亮, 袁正宏. 干扰素和核苷(酸)类似物治疗对HBV cccDNA的影响与慢性乙型肝炎的功能性治愈[J]. 临床肝胆病杂志, 2019, 35(6): 1181-1187. DOI: 10.3969/j.issn.1001-5256.2019.06.002 .
本文引用 [1]

作者贡献声明

蔡哲凯负责研究设计，数据整理，统计分析，文章撰写；张伟、吴敏负责样本收集，数据整理；刘文丽、钟青梅负责病理诊断，实验操作，资料整理；肖影群负责病理诊断质控及论文审阅；徐龙负责研究设计指导，论文审阅。

评论

PDF(671 KB)

Accesses

Citation

Detail
段落导航
相关文章
Copyright 中国高校科技期刊信息汇聚平台 2024-2025
技术支持：北京玛格泰克科技发展有限公司
京ICP备05021913号-19

/

〈 〉