The characteristics of the cell-mediated immune response identify different profiles of occult hepatitis B virus infection.
OBJECTIVE
Hepatitis B virus (HBV) DNA detection in serum and/or in the liver of hepatitis B surface antigen (HBsAg)-negative patients with or without serologic markers of previous viral exposure is defined as occult HBV infection. Because the role of the adaptive response in keeping HBV replication under control in occult infection still is undefined, this study was performed to characterize the features of the HBV-specific T-cell response in this condition.


METHODS
HBV-specific T-cell frequency and function were tested ex vivo and after in vitro expansion in 32 HBsAg-negative patients undergoing diagnostic liver biopsy for chronic hepatitis C: 18 with occult HBV infection (11 anti-HBc-negative and 7 anti-HBc-positive patients) defined by the detection of intrahepatic HBV DNA by polymerase chain reaction; 14 without detectable intrahepatic HBV DNA (5 anti-HBc-positive and 9 anti-HBc-negative patients). Six patients with chronic hepatitis B and 7 HBsAg-inactive carriers were studied for comparison.


RESULTS
The presence or absence of serologic HBV markers defined 2 profiles of HBV-specific T-cell responses in occult infection. Anti-HBc-positive patients showed a T-cell response typical of protective memory, suggesting that this condition represents a resolved infection with immune-mediated virus control. In contrast, HBV-specific T cells in anti-HBc-negative patients did not readily expand and produce interferon-gamma in vitro, suggesting the possibility of a low-dose infection insufficient to allow maturation of protective memory.


CONCLUSIONS
Our results suggest different mechanisms of control of viral replication in seropositive and seronegative occult infections. Additional studies aimed at understanding possible different clinical implications are needed.
Zerbini
Alessandro
A
Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Pilli
Massimo
M
Boni
Carolina
C
Fisicaro
Paola
P
Penna
Amalia
A
Di Vincenzo
Paola
P
Giuberti
Tiziana
T
Orlandini
Alessandra
A
Raffa
Giuseppina
G
Pollicino
Teresa
T
Raimondo
Giovanni
G
Ferrari
Carlo
C
Missale
Gabriele
G
D000328:Adult; D000368:Aged; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D008099:Liver / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012008:Recurrence; D014779:Virus Replication / Q000235:genetics*
D004279:DNA, Viral; D015789:HLA-A2 Antigen; D006514:Hepatitis B Surface Antigens