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.
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