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Liver sampling: a vital window into HBV pathogenesis on the path to functional cure


In order to optimally refine the multiple emerging drug targets for hepatitis B virus (HBV), it is vital to evaluate virological and immunological changes at the site of infection. Traditionally liver biopsy has been the mainstay of HBV disease assessment, but with the emergence of non-invasive markers of liver fibrosis, there has been a move away from tissue sampling. Here we argue that liver biopsy remains an important tool, not only for the clinical assessment of HBV but also for research progress and evaluation of novel agents. The importance of liver sampling has been underscored by recent findings of specialised subsets of tissue-resident immune subsets capable of efficient pathogen surveillance, compartmentalised in the liver and not sampled in the blood. Importantly, the assessment of virological parameters, such as cccDNA quantitation, also requires access to liver tissue. We discuss strategies to maximise information obtained from the site of infection and disease pathology. Fine needle aspirates of the liver may allow longitudinal sampling of the local virus/host landscape. The careful utilisation of liver tissue and aspirates in conjunction with blood will provide critical information in the assessment of new therapeutics for the functional cure of HBV.

  • cccDNA
  • fine needle aspirate
  • hepatitis B
  • hepatic fibrosis
  • histopathology
  • liver immunology
  • tissue resident cells
  • liver biopsy

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  • Funding The authors were supported by a Medical Research Council grant (G0801213) and a Wellcome Trust Senior Investigator Award and Enhancement (101849/Z/13/A) to MKM. Wellcome Trust Clinical Research Training Fellowship (107389/Z/15/Z) awarded to USG. A Barts and The London Charity Project Grant (723/1795) and an NIHR Research for patient benefit award (PB-PG-0614- 34087) to PTFK.

  • Competing interests USG has no conflicts of interest to declare; LJP has participated in a Gilead advisory board; PTFK has collaborative grant funding from Gilead, participates in advisory board/provides consultancy to Gilead, Janssen and is an investigator for industry-led trials with Gilead, Janssen, Alere, Assembly Biosciences. MKM’s laboratory has collaborative grant funding from Gilead and Roche; MKM participates in advisory boards/provides consultancy to Gilead, Roche, Arbutus Biopharma, Immunocore.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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