title: The characteristics of the cell-mediated immune response identify different profiles of occult hepatitis B virus infection.
abstract: 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.
authors: Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors: Alessandro
authors: A
authors: Zerbini
authors: Massimo
authors: M
authors: Pilli
authors: Carolina
authors: C
authors: Boni
authors: Paola
authors: P
authors: Fisicaro
authors: Amalia
authors: A
authors: Penna
authors: Paola
authors: P
authors: Di Vincenzo
authors: Tiziana
authors: T
authors: Giuberti
authors: Alessandra
authors: A
authors: Orlandini
authors: Giuseppina
authors: G
authors: Raffa
authors: Teresa
authors: T
authors: Pollicino
authors: Giovanni
authors: G
authors: Raimondo
authors: Carlo
authors: C
authors: Ferrari
authors: Gabriele
authors: G
authors: Missale
mesh_terms: 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*
chemical_list: D004279:DNA, Viral; D015789:HLA-A2 Antigen; D006514:Hepatitis B Surface Antigens