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The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection
  1. Clovis Palmer1,
  2. Theresa Corpuz1,
  3. Marianne Guirguis2,
  4. Sandra O'Toole3,
  5. Kenneth Yan2,
  6. Yagmin Bu2,
  7. John Jorgenson4,
  8. Michael Talbot4,
  9. Kenneth Loi4,
  10. Andrew Lloyd1,
  11. Amany Zekry1,2
  1. 1Centre for Infection and Inflammation Research, School of Medical Sciences, Sydney, Australia
  2. 2St George Hospital Clinical School, Sydney, Australia
  3. 3Cancer Research Program, Garvan Institute of Medical Research, Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia
  4. 4Division of Surgery, St George Hospital Clinical School, University of New South Wales, Sydney, Australia
  1. Correspondence to Dr Amany Zekry, School of Medicine, University of New South Wales, St George Hospital, Pitney Building, Belgrave Street, Kogarah, NSW 2217, Sydney, Australia; a.zekry{at}unsw.edu.au

Abstract

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

Objective In this study, we aimed to compare the hepatic 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, 25 with non-alcoholic fatty liver disease and 10 subjects with non-diseased liver.

Results Compared to the control groups, the liver injury in chronic hepatitis C was characterised by increased expression of several T-helper-1 cytokines including interferon-γ and tumour necrosis factor-α, and chemokines such as RANTES, IP-10 and MCP-1. In particular, in comparison with lean (BMI ≤25 kg/m2) HCV infected subjects, obese (BMI≥30 kg/m2) HCV infected subjects had increased hepatic expression of interferon-γ (p=0.004) and tumour necrosis factor-α (p<0.001), as well as increased expression of IP-10 (p=0.009) and MCP-1 (p<0.001). Localisation of these inflammatory chemokines revealed that in comparison to lean-HCV subjects, HCV infected liver from obese subjects exhibited significantly 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 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 T helper-1 cytokine response patterns—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 localisation of these chemokines within the liver of obese-HCV versus lean-HCV subjects—implying different inducing stimuli and; (4) increased CD3 expression in the liver of obese-HCV subjects—concordant with the increased expression of T cell chemoattractants.

  • Hepatitis C virus
  • obesity
  • TH-1 cytokines
  • chemokines
  • IP-10
  • MCP-1α
  • liver inflammation
  • steatosis

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Footnotes

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the St George Hospital in Sydney, Australia.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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