{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:25:02Z","timestamp":1790879102096,"version":"4.1.0"},"reference-count":65,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2000,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Upregulation of Th1 associated intrahepatic cytokines in chronic hepatitis C virus (HCV) infection should lead to a significant non-specific cellular immune response, a prerequisite for viral clearance. However, to date, the role of this non-specific response in HCV has been understudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>AIMS<\/jats:title>\n                    <jats:p>To analyse the intrahepatic macrophage activity in chronic HCV infection by immunostaining and by quantitation of cytokine mRNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"methods\">\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>HCV positive liver tissues (chronic hepatitis, n=10; cirrhosis, n=5) were immunostained for CD68, MAC387, and semiquantitated by polymerase chain reaction for intrahepatic cytokine mRNAs (interferon \u03b3 (IFN\u03b3), interleukin 1\u03b2 (IL-1\u03b2), IL-6, IL-18, tumour necrosis factor \u03b1 (TNF\u03b1), and macrophage inflammatory protein 1\u03b2 (MIP1\u03b2)). HCV negative normal liver tissues (for cytokines, n=6; for immunostaining, n=5) were included as controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      MAC387\n                      <jats:sup>+<\/jats:sup>\n                      cells were focally increased in areas of erosion at the limiting plate while lobular staining was minimal. CD68\n                      <jats:sup>+<\/jats:sup>\n                      staining was diffuse in both portal (increased in HCV) and lobular areas. The portal tract (mean) density of CD68\n                      <jats:sup>+<\/jats:sup>\n                      and MAC387\n                      <jats:sup>+<\/jats:sup>\n                      cells was significantly increased in patients with HCV compared with normal tissue. IFN\u03b3 and IL-18 mRNA levels were highly correlated and significantly upregulated in chronic hepatitis and cirrhotic tissue versus controls. TNF\u03b1 mRNA was upregulated in chronic hepatitis without cirrhosis, while IL-6 mRNA was significantly downregulated. IL-1\u03b2, IL-6, and MIP1\u03b2 mRNA levels were significantly correlated with portal tract MAC387\n                      <jats:sup>+<\/jats:sup>\n                      cell density.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The significant upregulation of IFN\u03b3 and IL-18 mRNA and significant correlations between IFN\u03b3 and other proinflammatory cytokines, suggest a Th1\/cell mediated intrahepatic immune response in chronic HCV infection. 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