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Intrahepatic cytokine profiles associated with posttransplantation hepatitis C virus–related liver injury

Authors

  • Amany Zekry,

    1. AW Morrow Gastroenterology and Liver Centre, New South Wales, Australia
    2. Liver Immunobiology Laboratory, Centenary Institute for Cancer and Cell Biology, New South Wales, Australia
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  • G. Alex Bishop,

    1. Liver Immunobiology Laboratory, Centenary Institute for Cancer and Cell Biology, New South Wales, Australia
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  • David G. Bowen,

    1. AW Morrow Gastroenterology and Liver Centre, New South Wales, Australia
    2. Liver Immunobiology Laboratory, Centenary Institute for Cancer and Cell Biology, New South Wales, Australia
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  • Margaret M. Gleeson,

    1. AW Morrow Gastroenterology and Liver Centre, New South Wales, Australia
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  • Seven Guney,

    1. AW Morrow Gastroenterology and Liver Centre, New South Wales, Australia
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  • Dorothy M. Painter,

    1. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney University, New South Wales, Australia
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  • Geoffrey W. McCaughan MD, PhD

    Corresponding author
    1. AW Morrow Gastroenterology and Liver Centre, New South Wales, Australia
    2. Liver Immunobiology Laboratory, Centenary Institute for Cancer and Cell Biology, New South Wales, Australia
    • The AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and University of Sydney, Missenden Rd, Camperdown 2050, Australia. Telephone: 61-295-155-857; FAX: 61-295-155-182
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Abstract

Recurrent chronic hepatitis, cholestatic hepatitis, and acute rejection in conjunction with hepatitis C virus (HCV) recurrence are well-recognized clinical sequelae of reinfection of the hepatic allograft with HCV. The aim of this study is to characterize intrahepatic cytokine responses associated with reinfection of the allograft with HCV in these settings. Intrahepatic messenger RNA expression of T helper cell subtype 1 (TH1) cytokines interleukin-2 (IL-2), interferon-γ, and tumor necrosis factor-α and TH2 cytokines IL-4 and IL-10 was measured by real-time polymerase chain reaction system using TaqMan probes in 53 liver specimens from six groups of patients. These were: (1) recurrent chronic hepatitis C (CH-I; n = 15), (2) cholestatic hepatitis (n = 6), (3) acute rejection associated with HCV recurrence (AR-HCV; n = 12), (4) acute rejection in non–HCV-infected allografts (AR non-HCV; n = 5), (5) patients with chronic hepatitis C who did not undergo transplantation (CH-C; n = 10), and (6) nondiseased liver tissue (n = 6). Intrahepatic viral loads were measured using an Amplicor monitor assay (Roche Diagnostic Systems, Branchburg, NJ). The CH-I and CH-C groups had similar TH1 intrahepatic cytokine profiles. Compared with the CH-I group, the cholestatic group expressed increased levels of the TH2 cytokines IL-10 (P = .024) and IL-4 (P = .0024). The AR-HCV group also expressed more TH2 cytokines IL-10 (P = .014) and IL-4 (P = .034) compared with the CH-I group. Both the AR-HCV and AR non-HCV groups showed similar intrahepatic cytokine profiles. Intrahepatic viral loads were highest in the cholestatic group compared with the AR-HCV, CH-I, and CH-C groups (P = .0007). In conclusion, a novel observation is that the cholestatic group showed upregulation of the TH2 cytokines IL-10 and IL-4, in addition to high viral loads. In this setting, the TH2 immune response may favor viral replication and graft damage.

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