Incubation Phase of Acute Hepatitis B in Man: Dynamic of Cellular Immune Mechanisms

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 incub...

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Veröffentlicht in:Hepatology (Baltimore, Md.) Md.), 2000-11, Vol.32 (5), p.1117-1124
Hauptverfasser: Webster, George J.M., Reignat, Stephanie, Maini, Mala K., Whalley, Simon A., Ogg, Graham S., King, Abigail, Brown, David, Amlot, Peter L., Williams, Roger, Vergani, Diego, Dusheiko, Geoffrey M., Bertoletti, Antonio
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container_end_page 1124
container_issue 5
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container_title Hepatology (Baltimore, Md.)
container_volume 32
creator Webster, George J.M.
Reignat, Stephanie
Maini, Mala K.
Whalley, Simon A.
Ogg, Graham S.
King, Abigail
Brown, David
Amlot, Peter L.
Williams, Roger
Vergani, Diego
Dusheiko, Geoffrey M.
Bertoletti, Antonio
description 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. (Hepatology 2000;32:1117-1124.)
doi_str_mv 10.1053/jhep.2000.19324
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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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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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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. (Hepatology 2000;32:1117-1124.)</abstract><cop>Philadelphia, PA</cop><pub>Elsevier Inc</pub><pmid>11050064</pmid><doi>10.1053/jhep.2000.19324</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Acute Disease
Adult
Aged
Antibody Formation
Biological and medical sciences
CD4-Positive T-Lymphocytes - physiology
CD8-Positive T-Lymphocytes - physiology
Disease Outbreaks
Female
Hepatitis B - epidemiology
Hepatitis B - immunology
Hepatitis B - pathology
Hepatitis B - virology
Human viral diseases
Humans
Immunity, Cellular
Infectious diseases
Liver - pathology
Liver - virology
Medical sciences
Middle Aged
United Kingdom
Viral diseases
Viral hepatitis
Virus Replication
title Incubation Phase of Acute Hepatitis B in Man: Dynamic of Cellular Immune Mechanisms
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