Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection

Marshall, Aileen, Rushbrook, Simon, Davies, Susan E., Morris, Lesley S., Scott, Ian S., Vowler, Sarah L., Coleman, Nicholas and Alexander, Graeme (2005) Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology, 128 (1). pp. 33-42. ISSN 0016-5085

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Abstract

Backgrounds & Aims: An increased risk of hepatitis C virus (HCV)-related cirrhosis is associated with hepatic steatosis, older age, and high alcohol consumption, which could be explained by synergistic effects on cell proliferation. We aimed to investigate hepatocyte cell cycle state and phase distribution in chronic HCV infection. Methods: Liver biopsy specimens diagnostic for chronic HCV (70), liver regeneration following transplant-related ischemic-reperfusion injury (15), and "normal" liver adjacent to colorectal cancer metastasis (10) were studied. Immunohistochemistry was used to detect cell cycle phase markers cyclin D1 (maximal in G1), cyclin A (S), cyclin B1 (cytoplasmic during G2) and phosphorylated histone 3 protein (mitosis), mini-chromosome maintenance protein 2 (Mcm-2; present throughout the cell cycle), and cyclin-dependent kinase inhibitor p21, which inhibits G1/S progression. Results: Hepatocyte Mcm-2 expression was elevated in chronic HCV and liver regeneration (13% vs 26.4%) but negligible in "normal" liver. In proportion to Mcm-2, there was no difference in cyclin D1 between chronic HCV infection and liver regeneration (51.6% of Mcm-2-positive hepatocytes vs 52.6%). In contrast, there was a striking reduction in cyclin A (3% vs 16.3%), cyclin B1 (.4% vs 2.3%), and phosphorylated histone 3 protein (0% vs 3.8%) in chronic HCV infection compared with liver regeneration. In chronic HCV infection, Mcm-2 and p21 expression were associated with fibrosis stage and positive serum HCV RNA. Conclusions: The data are consistent with hepatocyte G1 arrest in chronic HCV infection. This could impair hepatocellular function and limit hepatic regeneration.

Item Type:	Article
Uncontrolled Keywords:	hepatology,gastroenterology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2721
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	https://www.scopus.com/pages/publication...
Depositing User:	LivePure Connector
Date Deposited:	30 Jun 2026 13:22
Last Modified:	05 Jul 2026 23:02
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103531
DOI:	10.1053/j.gastro.2004.09.076

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