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258 Analysis of the Hepatic Microenvironment Before and After Direct-Acting Antiviral (DAA) Therapy for Viral Hepatitis C

Part of: JCTS_2023_ABSTRACT_COLLECTION

Published online by Cambridge University Press:  24 April 2023

Daniel Millian ,
Omar A. Saldarriaga ,
Esteban Arroyave ,
Timothy Wanninger ,
Santhoshi Krishnan ,
Arvind Rao ,
Akshata Moghe  and
Heather L. Stevenson
Daniel Millian
Affiliation:
Dept. of Pathology, University of Texas Medical Branch, Galveston, TX, USA
Omar A. Saldarriaga
Affiliation:
Dept. of Pathology, University of Texas Medical Branch, Galveston, TX, USA
Esteban Arroyave
Affiliation:
Dept. of Pathology, University of Texas Medical Branch, Galveston, TX, USA
Timothy Wanninger
Affiliation:
Dept. of Pathology, University of Texas Medical Branch, Galveston, TX, USA Dept. of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
Santhoshi Krishnan
Affiliation:
Dept. of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI Dept. of Electrical and Computer Engineering, Rice University, Houston, TX
Arvind Rao
Affiliation:
Dept. of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI Dept. of Electrical and Computer Engineering, Rice University, Houston, TX Dept. of Radiation Oncology, University of Michigan, Ann Arbor, MI
Akshata Moghe
Affiliation:
Dept. of Pathology, University of Texas Medical Branch, Galveston, TX, USA
Heather L. Stevenson
Affiliation:
Dept. of Pathology, University of Texas Medical Branch, Galveston, TX, USA
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Abstract

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OBJECTIVES/GOALS: The effect of the Direct-Acting Antiviral (DAA) on hepatic histopathological features from patients treated for HCV has not been thoroughly evaluated. The goals of this retrospective study were to determines differences between the liver biopsies collected before and after DAA treatment and correlated the histopathology with clinical outcome. METHODS/STUDY POPULATION: Spectral imaging was used to evaluate differences in intrahepatic macrophage (CD68, CD14, CD16, MAC 387, and CD163) and T cell (CD3, CD4, CD8, CD45, and FoxP3) phenotypes in paired liver biopsies collected from the same patient before (n=10) and after (n=10) achieving SVR (Figure 1). Imaging analysis and machine learning algorithms were used to evaluate changes in these key immune cells. We also compared differential gene expression of over 700 genes using RNA isolated from liver biopsies with NanoString. RESULTS/ANTICIPATED RESULTS: Multispectral imaging analysis showed a significant increase of proinflammatory/M1-like (e.g., CD14+) and anti-inflammatory/M2-like macrophage (e.g., CD163+) phenotypes in pre-treatment versus post-treatment biopsies, respectively. Gene expression analysis revealed enrichment of inflammatory (HLA-B, STAT1, CXCL10) and interferon induced-antiviral (ISG15, OAS3, MX1 and IFIT1) genes in the pre-treatment vs the post-treatment group. Cell deconvolution analysis also showed a significant increase of M1-like macrophages in the pre-treatment group when compared to the post-treatment group or controls. Upregulation of genes associated with cell proliferation and differentiation (c-KIT and Fos) was observed in the post-treatment biopsies of patients with persistent inflammatory infiltrates. DISCUSSION/SIGNIFICANCE: Protein and gene expression profiles observed in patients before DAA therapy showed a strong macrophage-mediated inflammatory response against HCV infection in the liver that shifted significantly to a tissue remodeling microenvironment after treatment.

Type
Precision Medicine/Health
Information
Journal of Clinical and Translational Science , Volume 7 , Issue s1 , April 2023 , pp. 78 - 79
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2023. The Association for Clinical and Translational Science