1. Academic Validation
  2. Impact of metformin on HBV replication: No evidence of suppression in vitro

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

  • J Clin Virol. 2025 Mar 17:177:105781. doi: 10.1016/j.jcv.2025.105781.
Cyrus Hawkins 1 Elizabeth Waddilove 1 Philippa C Matthews 2 Marion Delphin 3
Affiliations

Affiliations

  • 1 The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 2 The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK; Department of Infectious Diseases, University College London Hospital, Euston Road, London NW1 2BU, UK.
  • 3 The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: marion.delphin@crick.ac.uk.
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.

Keywords

Hepatitis B Virus; MASLD; Metabolic syndrome; Metformin; Replication; Suppression.

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