Abstract
ObjectiveIn order to refine new therapeutic strategies in the pipeline for HBV cure, evaluation of virological and immunological changes compartmentalised at the site of infection will be required. We therefore investigated if liver fine needle aspirates (FNAs) could comprehensively sample the local immune landscape in parallel with viable hepatocytes.DesignMatched blood, liver biopsy and FNAs from 28 patients with HBV and 15 without viral infection were analysed using 16-colour multiparameter flow cytometry.ResultsThe proportion of CD4 T, CD8 T, Mucosal Associated Invariant T cell (MAIT), Natural Killer (NK) and B cells identified by FNA correlated with that in liver biopsies from the same donors. Populations of Programmed Death-1 (PD-1)hiCD39hi tissue-resident memory CD8 T cells (CD69+CD103+) and liver-resident NK cells (CXCR6+T-betloEomeshi), were identified by both FNA and liver biopsy, and not seen in the blood. Crucially, HBV-specific T cells could be identified by FNAs at similar frequencies to biopsies and enriched compared with blood. FNAs could simultaneously identify populations of myeloid cells and live hepatocytes expressing albumin, Scavenger Receptor class B type 1 (SR-B1), Programmed Death-Ligand 1 (PD-L1), whereas hepatocytes were poorly viable after the processing required for liver biopsies.ConclusionWe demonstrate for the first time that FNAs identify a range of intrahepatic immune cells including locally resident sentinel HBV-specific T cells and NK cells, together with PD-L1-expressing hepatocytes. In addition, we provide a scoring tool to estimate the extent to which an individual FNA has reliably sampled intrahepatic populations rather than contaminating blood. The broad profiling achieved by this less invasive, rapid technique makes it suitable for longitudinal monitoring of the liver to optimise new therapies for HBV.
Highlights
Chronic hepatitis B virus (HBV) is estimated to affect 280 million people worldwide and continues to kill more than 700 000 a year.[1]
Mucosal Associated Invariant T cell (MAIT) were significantly enriched in the liver compartment and we observed a striking correlation in frequencies detected within an individual by fine needle aspirates (FNAs) versus biopsy
A similar liver enrichment was seen for Natural Killer (NK) cells (CD3−CD56+), which showed a robust correlation between FNA and biopsy frequencies
Summary
Chronic hepatitis B virus (HBV) is estimated to affect 280 million people worldwide and continues to kill more than 700 000 a year.[1]. Existing antivirals can rarely achieve sustained off-treatment responses but new therapies are in development, aiming to achieve a ‘functional cure’.2 This is defined by Hepatitis B Surface Antigen (HBsAg) loss and represents the situation where the majority of infection is cleared and residual intrahepatic HBV covalently
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