Impact of metformin on HBV replication: No evidence of suppression in vitro

IF 4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology Pub Date : 2025-03-17 DOI:10.1016/j.jcv.2025.105781

Cyrus Hawkins , Elizabeth Waddilove , Philippa C. Matthews , Marion Delphin

{"title":"Impact of metformin on HBV replication: No evidence of suppression in vitro","authors":"Cyrus Hawkins , Elizabeth Waddilove , Philippa C. Matthews , Marion Delphin","doi":"10.1016/j.jcv.2025.105781","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Outcomes of chronic Hepatitis B (CHB) infection have been increasingly associated with various metabolic syndromes, including metabolic-dysfunction associated steatotic liver disease (MASLD), with a potential for impact on liver disease progression. There is some evidence that metformin, a widely used anti-diabetic drug, may reduce hepatocellular carcinoma (HCC) incidence in people living with Hepatitis B Virus (HBV), but with little to no evidence of impact on the virus itself <em>in vivo</em>. However, previous <em>in vitro</em> studies suggest metformin may have a direct impact on HBV replication, although the mechanism remains unclear.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the impact of metformin on HBV replication <em>in vitro</em>.</div></div><div><h3>Study design</h3><div>Hepatocyte cell lines constitutively expressing HBV (HepAD38) were treated once or thrice with escalating doses of metformin, using lamivudine and water as controls. We monitored cellular cytotoxicity as well as HBV biomarkers (HBeAg, HBsAg, HBV DNA and RNA) throughout the assay.</div></div><div><h3>Results</h3><div>We did not observe any impact of metformin on HBV replication after a single dose or three repeated treatments.</div></div><div><h3>Conclusions</h3><div>In HepAD38 cells, HBV replication is not impacted by metformin treatment. This contrasts with prior <em>in vitro</em> data but is in line with clinical evidence that suggests metformin acts through an influence on liver disease progression rather than a direct antiviral impact on HBV itself.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105781"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Virology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1386653225000228","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Outcomes of chronic Hepatitis B (CHB) infection have been increasingly associated with various metabolic syndromes, including metabolic-dysfunction associated steatotic liver disease (MASLD), with a potential for impact on liver disease progression. There is some evidence that metformin, a widely used anti-diabetic drug, may reduce hepatocellular carcinoma (HCC) incidence in people living with Hepatitis B Virus (HBV), but with little to no evidence of impact on the virus itself in vivo. However, previous in vitro studies suggest metformin may have a direct impact on HBV replication, although the mechanism remains unclear.

Objectives

We aimed to investigate the impact of metformin on HBV replication in vitro.

Study design

Hepatocyte cell lines constitutively expressing HBV (HepAD38) were treated once or thrice with escalating doses of metformin, using lamivudine and water as controls. We monitored cellular cytotoxicity as well as HBV biomarkers (HBeAg, HBsAg, HBV DNA and RNA) throughout the assay.

Results

We did not observe any impact of metformin on HBV replication after a single dose or three repeated treatments.

Conclusions

In HepAD38 cells, HBV replication is not impacted by metformin treatment. This contrasts with prior in vitro data but is in line with clinical evidence that suggests metformin acts through an influence on liver disease progression rather than a direct antiviral impact on HBV itself.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Clinical Virology 医学-病毒学

CiteScore

22.70

自引率

1.10%

发文量

149

审稿时长

24 days

期刊介绍： The Journal of Clinical Virology, an esteemed international publication, serves as the official journal for both the Pan American Society for Clinical Virology and The European Society for Clinical Virology. Dedicated to advancing the understanding of human virology in clinical settings, the Journal of Clinical Virology focuses on disseminating research papers and reviews pertaining to the clinical aspects of virology. Its scope encompasses articles discussing diagnostic methodologies and virus-induced clinical conditions, with an emphasis on practicality and relevance to clinical practice. The journal publishes on topics that include: • new diagnostic technologies • nucleic acid amplification and serologic testing • targeted and metagenomic next-generation sequencing • emerging pandemic viral threats • respiratory viruses • transplant viruses • chronic viral infections • cancer-associated viruses • gastrointestinal viruses • central nervous system viruses • one health (excludes animal health)