Genomic Integration of Hepatitis B Virus Into Human Hepatocytes in Early Childhood Cirrhosis

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-03-25 DOI:10.1111/liv.70080

Ying Chen, Yi Dong, Shizhang Wei, Xue Gao, Weijie Li, Pan Zhao

{"title":"Genomic Integration of Hepatitis B Virus Into Human Hepatocytes in Early Childhood Cirrhosis","authors":"Ying Chen, Yi Dong, Shizhang Wei, Xue Gao, Weijie Li, Pan Zhao","doi":"10.1111/liv.70080","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>Hepatitis B virus (HBV) remains a major global health problem. HBV DNA can be integrated into the human chromosomes. The integration in young cirrhotic chronic hepatitis B children has not been explored. This study aims to investigate HBV DNA integration in early childhood cirrhosis.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Biopsy liver specimens from cirrhotic and matched non-cirrhotic chronic hepatitis B children were collected. HBV DNA integration was detected through targeted HBV DNA fragment capture sequencing.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Twenty cirrhotic and 20 non-cirrhotic children with chronic hepatitis B were included in the study. The cirrhotic group included 14 males and 6 females, and the non-cirrhotic group included 13 males and 7 females. Compared to non-cirrhotic children, cirrhotic children had lower serum HBsAg quantification (<i>p</i> = 0.001). The median number of HBV integrants in the cirrhotic group was 59 and that in the non-cirrhotic group was 98. No significant difference existed between the two groups (<i>p</i> = 0.529). In the multivariate linear regression analysis, serum HBV DNA level was correlated with the number of HBV integrants (<i>p</i> < 0.001, <i>R</i><sup>2</sup> = 0.322). Six differential intragenic high-frequency viral integration sites in cirrhotic children were revealed, all of which have protein-coding functions.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Several frequently integrated genes were observed in early childhood cirrhosis. Detailed associations between genetic alterations induced by HBV integration and early childhood cirrhosis need further exploration.</p>\n </section>\n </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.70080","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and Aims

Hepatitis B virus (HBV) remains a major global health problem. HBV DNA can be integrated into the human chromosomes. The integration in young cirrhotic chronic hepatitis B children has not been explored. This study aims to investigate HBV DNA integration in early childhood cirrhosis.

Methods

Biopsy liver specimens from cirrhotic and matched non-cirrhotic chronic hepatitis B children were collected. HBV DNA integration was detected through targeted HBV DNA fragment capture sequencing.

Results

Twenty cirrhotic and 20 non-cirrhotic children with chronic hepatitis B were included in the study. The cirrhotic group included 14 males and 6 females, and the non-cirrhotic group included 13 males and 7 females. Compared to non-cirrhotic children, cirrhotic children had lower serum HBsAg quantification (p = 0.001). The median number of HBV integrants in the cirrhotic group was 59 and that in the non-cirrhotic group was 98. No significant difference existed between the two groups (p = 0.529). In the multivariate linear regression analysis, serum HBV DNA level was correlated with the number of HBV integrants (p < 0.001, R² = 0.322). Six differential intragenic high-frequency viral integration sites in cirrhotic children were revealed, all of which have protein-coding functions.

Conclusion

Several frequently integrated genes were observed in early childhood cirrhosis. Detailed associations between genetic alterations induced by HBV integration and early childhood cirrhosis need further exploration.

查看原文本刊更多论文

背景和目的乙型肝炎病毒（HBV）仍然是一个重大的全球健康问题。HBV DNA 可以整合到人类染色体中。目前尚未对慢性乙型肝炎幼年肝硬化儿童的整合情况进行研究。本研究旨在调查儿童早期肝硬化中的 HBV DNA 整合情况。方法收集肝硬化和匹配的非肝硬化慢性乙型肝炎儿童的活检肝脏标本。通过靶向 HBV DNA 片段捕获测序检测 HBV DNA 整合。结果研究纳入了 20 名肝硬化和 20 名非肝硬化慢性乙型肝炎患儿。肝硬化组包括 14 名男性和 6 名女性，非肝硬化组包括 13 名男性和 7 名女性。与非肝硬化儿童相比，肝硬化儿童的血清 HBsAg 定量较低（P = 0.001）。肝硬化组 HBV 整合子的中位数为 59 个，非肝硬化组为 98 个。两组之间无明显差异（p = 0.529）。在多变量线性回归分析中，血清 HBV DNA 水平与 HBV 整合子数量相关（p < 0.001，R2 = 0.322）。在肝硬化患儿中发现了六个不同的基因内高频病毒整合位点，所有这些位点都具有编码蛋白质的功能。结论在儿童早期肝硬化中观察到几个高频整合基因。HBV 整合诱导的基因改变与儿童早期肝硬化之间的详细联系需要进一步探讨。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.