title: Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis.
abstract: Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extra-hepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-α and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (Treg) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic Treg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA.|Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Helal F
authors.initials: HF
authors.lastname: Hetta
authors.affiliation: Department of Gastroenterology & Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Mekky
authors.affiliation: Assiut Liver Institute for Treatment of Hepatitis C, Assiut, Egypt.
authors.forename: Nasr K
authors.initials: NK
authors.lastname: Khalil
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Wegdan A
authors.initials: WA
authors.lastname: Mohamed
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Feky
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Shabaan H
authors.initials: SH
authors.lastname: Ahmed
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Enas A
authors.initials: EA
authors.lastname: Daef
authors.affiliation: Department of Gastroenterology & Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Medhat
authors.affiliation: Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mahmoud I
authors.initials: MI
authors.lastname: Nassar
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Mohamed Tarek M
authors.initials: MTM
authors.lastname: Shata
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000821:virology; D001706:Biopsy; D003106:Colon / Q000821:virology*; D003430:Cross-Sectional Studies; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology; D008264:Macrophages / Q000821:virology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D055815:Young Adult