{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:36:54Z","timestamp":1787319414080,"version":"build-2736575974"},"reference-count":37,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obese subjects with chronic hepatitis C virus (HCV) infection have more rapidly progressive liver disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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-\u03b3 and tumour necrosis factor-\u03b1, and chemokines such as RANTES, IP-10 and MCP-1. In particular, in comparison with lean (BMI \u226425\u2005kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) HCV infected subjects, obese (BMI\u226530\u2005kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) HCV infected subjects had increased hepatic expression of interferon-\u03b3 (p=0.004) and tumour necrosis factor-\u03b1 (p&lt;0.001), as well as increased expression of IP-10 (p=0.009) and MCP-1 (p&lt;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&lt;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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2014to promote hepatocellular injury; (2) increased expression of the chemokines IP-10 and MCP-1 at both the mRNA and protein levels\u2014to enhance inflammatory cell recruitment; (3) differing localisation of these chemokines within the liver of obese-HCV versus lean-HCV subjects\u2014implying different inducing stimuli and; (4) increased CD3 expression in the liver of obese-HCV subjects\u2014concordant with the increased expression of T cell chemoattractants.<\/jats:p>\n                  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