Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms - PubMed (original) (raw)
. 2000 Nov;32(5):1117-24.
doi: 10.1053/jhep.2000.19324.
S Reignat, M K Maini, S A Whalley, G S Ogg, A King, D Brown, P L Amlot, R Williams, D Vergani, G M Dusheiko, A Bertoletti
Affiliations
- PMID: 11050064
- DOI: 10.1053/jhep.2000.19324
Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms
G J Webster et al. Hepatology. 2000 Nov.
Abstract
After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease.
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