PMID- 11050064
OWN - NLM
STAT- MEDLINE
DCOM- 20001121
LR  - 20220408
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 32
IP  - 5
DP  - 2000 Nov
TI  - Incubation phase of acute hepatitis B in man: dynamic of cellular immune 
      mechanisms.
PG  - 1117-24
AB  - 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.
FAU - Webster, G J
AU  - Webster GJ
AD  - Centre for Hepatology, Departments of Medicine, Royal Free Campus, Royal Free and 
      University College Medical School, London, UK.
FAU - Reignat, S
AU  - Reignat S
FAU - Maini, M K
AU  - Maini MK
FAU - Whalley, S A
AU  - Whalley SA
FAU - Ogg, G S
AU  - Ogg GS
FAU - King, A
AU  - King A
FAU - Brown, D
AU  - Brown D
FAU - Amlot, P L
AU  - Amlot PL
FAU - Williams, R
AU  - Williams R
FAU - Vergani, D
AU  - Vergani D
FAU - Dusheiko, G M
AU  - Dusheiko GM
FAU - Bertoletti, A
AU  - Bertoletti A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Aged
MH  - Antibody Formation
MH  - CD4-Positive T-Lymphocytes/physiology
MH  - CD8-Positive T-Lymphocytes/physiology
MH  - Disease Outbreaks
MH  - Female
MH  - Hepatitis B/epidemiology/*immunology/pathology/virology
MH  - Humans
MH  - *Immunity, Cellular
MH  - Liver/pathology/virology
MH  - Middle Aged
MH  - United Kingdom
MH  - Virus Replication
EDAT- 2000/10/26 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/26 11:00
PHST- 2000/10/26 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/26 11:00 [entrez]
AID - S0270913900686512 [pii]
AID - 10.1053/jhep.2000.19324 [doi]
PST - ppublish
SO  - Hepatology. 2000 Nov;32(5):1117-24. doi: 10.1053/jhep.2000.19324.