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

Abstract

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.

Keywords: cccDNA; fine needle aspirate; hepatic fibrosis; hepatitis B; histopathology; liver biopsy; liver immunology; tissue resident cells.

Figure 1

Historical progression of the modality of liver disease assessment as outlined in national and international clinical practice guidelines for hepatitis B virus. CHB, chronic hepatitis B; NICE, National Institute for Health and Care Excellence; TE, transient elastography.

Figure 2

Schematic of A) peripheral and B) intrahepatic lymphocyte populations depicting examples that can be sampled from both sites but have an exagerated phenotype in the liver and others that are unique to the liver.

Figure 3

Relative frequencies of lymphocyte subsets between the blood and the liver (key indicates relative abundance between the two sites, not between different cell types).