Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells

作者：Abhishek Aggarwal, Pamela M. Odorizzi, Jens Brodbeck, Nicholas van Buuren, Christina Moon, Silvia Chang, MaryVic Adona, Silpa Suthram, Vithika Suri, Torsten Trowe, Scott Turner, Patrick Marcellin, Marı́a Buti, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Becket Feierbach, Scott Balsitis · 发表于：JHEP Reports · 年份：2022 · DOI：10.1016/j.jhepr.2022.100664 · 被引用次数：26 · 研究领域：Hepatitis B Virus Studies、Liver physiology and pathology、Hepatitis C virus research

Background & Aims: Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers. Methods: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n = 39) and HBeAg-negative (n = 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA. Results: Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive par...