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ToolsFreeman, A., Hamid, S., Morris, L., Vowler, S., Rushbrook, S., Wight, D. G.D., Coleman, N. and Alexander, G. J.M. (2003) Improved detection of hepatocyte proliferation using antibody to the pre-replication complex:An association with hepatic fibrosis and viral replication in chronic hepatitis C virus infection. Journal of Viral Hepatitis, 10 (5). pp. 345-350. ISSN 1352-0504
Full text not available from this repository. (Request a copy)Abstract
To test the hypothesis that hepatitis C virus (HCV) might induce hepatocyte proliferation directly, thereby pre-disposing HCV carriers to cirrhosis and hepatocellular carcinoma, we have used a new method to identify proliferating hepatocytes, employing a novel monoclonal antibody to minichromosome maintenance (Mcm) proteins, essential components of the pre-replication complex. Antibody to Ki-67, a conventional marker of cell division, was also studied. Eighty-seven patients with chronic HCV infection and a broad spectrum of histological change were studied. Proliferation was observed rarely in hepatocytes from normal liver from healthy controls (always less than 0.01%). However, proliferating hepatocytes were detected in all HCV-infected patients and the proportion of hepatocytes expressing Mcm-2 (3-40%) always exceeded that expressing Ki-67 (1-14%) and correlated positively with increasing stage of fibrosis (P = 0.0001) and viral replication (P = 0.0004). There were weaker but significant associations between the proportion of hepatocytes expressing Mcm-2 and inflammatory indices including interface hepatitis, portal tract inflammation, lobular inflammation and steatosis. There was no association between the proportion of hepatocytes expressing Mcm-2 and age, gender or past alcohol consumption, but there was a weak association with current consumption of alcohol (P = 0.0067). The proportion of Ki-67 hepatocytes did not correlate with any clinical, laboratory or histological parameter. Mcm-2 was also detected in bile duct cells, sinusoidal lining cells and infiltrating lymphocytes, but at low frequency. These data indicate first, that Mcm-2 is a more sensitive marker of hepatocyte proliferation than Ki-67, second that many hepatocytes in chronic HCV infection have entered the cell cycle and third, suggest that interference with the hepatocyte cell cycle might be an alternative approach to therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cell cycle,disease progression,dna proliferation,hepatitis c,natural history,hepatology,infectious diseases,virology ,/dk/atira/pure/subjectarea/asjc/2700/2721 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 30 Jun 2026 13:19 |
| Last Modified: | 01 Jul 2026 07:33 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/103525 |
| DOI: | 10.1046/j.1365-2893.2003.00454.x |
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