Article Text

other Versions

PDF
The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection
  1. Clovis Palmer (c.palmer{at}unsw.edu.au)
  1. University of New South Wales, Australia
    1. Theresa Corpuz
    1. University of New South Wales, Australia
      1. Marianne Guirguis
      1. St George Hospital Clinical School, University of New South Wales, Australia
        1. Sandra O’Toole
        1. Garvan Institute of Medical Research, Australia
          1. Kennath Yan
          1. St George Hospital Clinical School, University of New South Wales, Australia
            1. Yang Min Bu
            1. St George Hospital Clinical School, University of New South Wales, Australia
              1. John Jorgenson
              1. Division of Surgery, St George Hospital, Australia
                1. Michael Talbot
                1. Division of Surgery, St George Hospital, Australia
                  1. Andrew Lloyd
                  1. School of Medical Sciences, University of New South Wales, Australia
                    1. Amany Zekry (a.zekry{at}unsw.edu.au)
                    1. St George Hospital Clinical School, University of New South Wales, Australia

                      Abstract

                      Background: Obese subjects with chronic hepatitis C virus (HCV) infection have more rapidly progressive liver disease.

                      Objective: We aimed to compare the intrahepatic cytokine and chemokine profiles in obese and lean subjects with chronic HCV infection using qRT-PCR and immunohistochemistry.

                      Methods: Liver biopsies from 55 subjects were studied, including 20 with chronic hepatitis C (CHC), 25 with non-alcoholic fatty liver disease (NAFLD) and 10 non-diseased liver.

                      Results: Compared to the control groups, the liver injury in CHC was characterized by increased expression of interferon (IFN)-γ and tumour necrosis factor (TNF)-α, and chemokines such as RANTES, IP-10 and MCP-1. In comparison with lean -HCV infected subjects, obese-HCV infected subjects had increased hepatic expression of IFN-γp=0.004) and TNF-α(p<0.001) as well as increased expression of IP-10 (p=0.009) and MCP-1 (p<0.001). Localization of these inflammatory chemokines revealed that in comparison to lean-HCV subjects, HCV infected liver from obese subjects exhibited increased expression of IP-10 (p<0.001) and MCP-1 (p=0.02) in the inflammatory infiltrate of the portal tracts. In parallel, there was increased CD3+ T cell infiltration in the liver of obese-HCV subjects.

                      Conclusions: The data provide important mechanistic information on the cause of hepatic injury in obese-HCV subjects including: 1) enhanced TH-1 cytokine response-to promote hepatocellular injury; 2) increased expression of the chemokines IP-10 and MCP-1 at both the mRNA and protein levels-to enhance inflammatory cell recruitment; 3) differing localization of these chemokines within the liver of obese-HCV versus lean-HCV subjects and; 4) increased CD3+ cells expression in the liver of obese-HCV subject.

                      Statistics from Altmetric.com

                      Request permissions

                      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

                      Linked Articles

                      • Digest
                        Emad El-Omar Severine Vermeire Alexander Gerbes