Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection

作者：Nicholas van Buuren, Ricardo Ramírez, Scott Turner, Diana Chen, Vithika Suri, Abhishek Aggarwal, Christina Moon, Samuel Kim, Dmytro Kornyeyev, Nam Bui, Neeru Bhardwaj, Henry LY Chan, Patrick Marcellin, Marı́a Buti, Jeffrey J. Wallin, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Li Li, Hongmei Mo, Becket Feierbach · 发表于：JHEP Reports · 年份：2021 · DOI：10.1016/j.jhepr.2021.100388 · 被引用次数：52 · 研究领域：Hepatitis B Virus Studies、Liver physiology and pathology、Liver Disease Diagnosis and Treatment

BACKGROUND & AIMS: We aim to describe the liver immune microenvironment by analyzing liver biopsies from patients with chronic HBV infection (CHB). Host immune cell signatures and their corresponding localization were characterized by analyzing the intrahepatic transcriptome in combination with a custom multiplex immunofluorescence panel. METHOD: Matching FFPE and fresh frozen liver biopsies were collected from immune active patients within the open-label phase IV study GS-US-174-0149. RNA-Seq was conducted on 53 CHB liver biopsies from 46 patients. Twenty-eight of the 53 samples had matched FFPE biopsies and were stained with a 12-plex panel including cell segmentation, immune and viral biomarkers. Corresponding serum samples were screened using the MSD Human V-plex Screen Service to identify peripheral correlates for the immune microenvironment. RESULTS: Using unsupervised clustering of the transcriptome, we reveal two unique liver immune signatures classified as immune high and immune low based on the quantification of the liver infiltrate gene signatures. Multiplex immunofluorescence analysis demonstrated large periportal lymphoid aggregates in immune high samples consisting of CD4 and CD8 T cells, B cells and macrophages. Differentiation of the high and low immune microenvironments was independent of HBeAg status and peripheral viral antigen levels. In addition, longitudinal analysis indicates that treatment and normalization of ALT correlates with a decrease in liver im...