These authors contributed equally to this study.
Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia†
Article first published online: 11 AUG 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Volume 48, Issue 4, pages 1079–1086, October 2008
How to Cite
Dandri, M., Murray, J. M., Lutgehetmann, M., Volz, T., Lohse, A. W. and Petersen, J. (2008), Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia. Hepatology, 48: 1079–1086. doi: 10.1002/hep.22469
Potential conflict of interest: Nothing to report.
- Issue published online: 26 SEP 2008
- Article first published online: 11 AUG 2008
- Manuscript Accepted: 5 JUN 2008
- Manuscript Received: 20 DEC 2007
- Deutsche Forschungsgemeinschaft. Grant Number: Pe/608 2-5
- European Union Vigilance Network (6th framework program) for the Management of Antiviral Drug Resistance (Virgil)
Analysis of hepatitis B virus (HBV) kinetics with mathematical models may disclose new aspects of HBV infection and host response mechanisms. To determine the kinetics of virion decay from the blood of patients in different phases of chronic infection, we applied mathematical modeling to real-time polymerase chain reaction assays, which enable quantification of viremia and intrahepatic HBV productivity by measuring both copy number and activity of covalently closed circular DNA (relaxed circular DNA/covalently closed circular DNA) in the liver of 80 untreated chronically active HBV carriers (38 hepatitis B e antigen [HBeAg]-positive and 42 HBeAg-negative individuals). We found that the half-life of circulating virions is very fast (median 46 and 2.5 minutes in HBeAg-positive and HBeAg-negative individuals, respectively) and strongly related to viremia, with clearance rates significantly accelerating as viral loads decrease. To investigate whether immune components can influence the kinetics of virion decay, we analyzed viral dynamics in immunodeficient urokinase-type plasminogen activator chimera mice. Virion half-life in mice (range, 44 minutes to >4 hours) was comparable to estimates determined in high viremic carriers, implying that clearance rates in these patients are mostly determined by common nonspecific mechanisms. Notably, the lack of correlation between virion half-life and viremia in mice indicated that immune components significantly accelerate virion clearance rates in individuals with low titers. Conclusion: Our analyses suggest that both host defense mechanisms and levels of circulating virions affect the kinetics of HBV decay assessed in the serum of chronic carriers. Identification of the factors affecting clearance rates will be important for future antiviral drug developments and it may give insights into the mechanisms involved in clearance of other chronic infections, such as human immunodeficiency virus and hepatitis C virus. (HEPATOLOGY 2008.)