Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection Authors Nicholas van Buuren, Ricardo Ramirez, Scott Turner, Diana Chen, Vithika Suri, Abhishek Aggarwal, Christina Moon, Sam Kim, Dmytro Kornyeyev, Nam Bui, Neeru Bhardwaj, Henry LYChan, Patrick Marcellin, Maria Buti, Jeffrey Wallin, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Li Li, Hongmei Mo, Becket Feierbach Correspondence [email protected] (B. Feierbach). Graphical abstract Multiplex IF RNA-Seq Immune High Immune Low Liver biopsy T T cells B B cells PD-1/PD-L1 Immune markers Nuclei Highlights Two different liver immune microenvironments were identified in patients with chronic hepatitis B: immune high and immune low. Immune high patients had elevated immune pathway activity and immune cell signatures cor- responding to B cells, T cells and macrophages. Antiviral treatment and normalization of ALT cor- relates with a marked decrease in liver immune infiltrate and inflammation. CXCL10 and ICAM-1 were identified as peripheral biomarkers that correlated with these differenti- ated immune microenvironments. Lay summary Liver biopsies from patients with chronic hepatitis B were submitted to RNA-Seq and multiplex immuno- fluorescence and identified two different liver im- mune microenvironments: immune high and immune low. Immune high patients showed elevated immune pathways, including interferon signaling pathways, and increase presence of immune cells. Longitudinal analysis of biopsies from treatment experienced pa- tients showed that treatment correlates with a marked decrease in inflammation and these findings may have important implications for both safety and efficacy of immune modulator programs for HBV cure. https://doi.org/10.1016/j.jhepr.2021.100388 Research article
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