437. Toll-Like Receptor 7 and Interferon Lambda 1 in Patients with Chronic Hepatitis C: Relation to Virus Replication and Liver Injury.
Session: Poster Abstract Session: Hepatitis C
Thursday, October 27, 2016
Room: Poster Hall
Posters
  • Dr. Hoda El Aggan poster # 437.pdf (6.8 MB)
  • Background: Toll-like receptor 7 (TLR7) recognizes single-stranded RNA viruses like hepatitis C virus (HCV) with subsequent induction of interferons (IFN) including IFN lambdas (IFN-λs), which play an important role in antiviral innate immunity. The present work was designed to study the role of TLR7 and IFN-λ1 in chronic hepatitis C (CHC) in relation to virus replication and liver injury.

    Methods: Forty two treatment-naïve patients with CHC and 20 healthy subjects were included in the study. Liver biopsies were examined to assess METAVIR histological activity grade and fibrosis stage and steatosis grade. Immunohistochemical staining was performed using antibodies against TLR7 and IFN-λ1 and was scored semi-quantitatively (score 0-3). Hepatic expression of TLR7 and IFN-l1 was further classified into: low expression (score 0 or 1) and high expression (score 2 or 3). The TLR7-expressing peripheral blood mononuclear cells (PBMCs) were identified by color flow cytometry as CD14+TLR7+ cells and were expressed as percentages of total lymphocyte count. Quantification of IFN-λ1 levels in serum was performed using enzyme-linked immunosorbant assay.

    Results: In patients with CHC, the expression of TLR7 and IFN-λ1 in the liver was low in 35.7% and 23.8% of patients respectively and high in 64.3% and 76.2% of patients respectively. Patients with low hepatic TLR7 and IFN-λ1 expression showed significant decreases in the percentages of TLR7-expressing PBMCs and serum IFN-λ1 levels and significant increases in serum levels of aminotransferases, viral load and METAVIR histologic activity grade and fibrosis stage compared with patients with high expression (P < 0.01). TLR7 expression in the liver showed positive correlations with the percentages of TLR7-expressing PBMCs and the serum levels and hepatic expression of IFN-λ1 (P < 0.001). The percentages of TLR7-expressing PBMCs and serum IFN-λ1 levels were also positively correlated (P< 0.001).

    Conclusion: Dysregulation of TLR7/IFN-λ1 pathway in CHC seems to play an important role in viral replication and HCV-related liver injury and could be a potential therapeutic target in chronic HCV infection.

    Hoda El Aggan, Professor of Medicine1, Nahla Farahat, Professor of Clinical Pathology2, Nevine El Deeb, Professor of Pathology3, Ahmed Zeid, Assistant Professor of Medicine1 and Assem El Sandidi, Lecturer of Medicine1, (1)Department of Medicine (Hepatobiliary Unit), Faculty of Medicine, University of Alexandria, Alexandria, Egypt, (2)Department of Clinical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt, (3)Department of Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

    Disclosures:

    H. El Aggan, None

    N. Farahat, None

    N. El Deeb, None

    A. Zeid, None

    A. El Sandidi, None

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