The Characteristics of the Cell-Mediated Immune Response Identify Different Profiles of Occult Hepatitis B Virus Infection

Alessandro Zerbini, Massimo Pilli, Carolina Boni, Paola Fisicaro, Amalia Penna, Paola Di Vincenzo, Tiziana Giuberti, Alessandra Orlandini, Giuseppina Raffa, Teresa Pollicino, Giovanni Raimondo, Carlo Ferrari, Gabriele Missale

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Abstract

Background& Aims: 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-γ 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.

Original languageEnglish
Pages (from-to)1470-1481
Number of pages12
JournalGastroenterology
Volume134
Issue number5
DOIs
Publication statusPublished - May 2008

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Virus Diseases
Hepatitis B virus
T-Lymphocytes
Hepatitis B Surface Antigens
Infection
Liver
DNA
Chronic Hepatitis B
Chronic Hepatitis C
DNA-Directed DNA Polymerase
Virus Replication
Interferons
Biomarkers
Viruses
Biopsy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Zerbini, A., Pilli, M., Boni, C., Fisicaro, P., Penna, A., Di Vincenzo, P., ... Missale, G. (2008). The Characteristics of the Cell-Mediated Immune Response Identify Different Profiles of Occult Hepatitis B Virus Infection. Gastroenterology, 134(5), 1470-1481. https://doi.org/10.1053/j.gastro.2008.02.017

The Characteristics of the Cell-Mediated Immune Response Identify Different Profiles of Occult Hepatitis B Virus Infection. / Zerbini, Alessandro; Pilli, Massimo; Boni, Carolina; Fisicaro, Paola; Penna, Amalia; Di Vincenzo, Paola; Giuberti, Tiziana; Orlandini, Alessandra; Raffa, Giuseppina; Pollicino, Teresa; Raimondo, Giovanni; Ferrari, Carlo; Missale, Gabriele.

In: Gastroenterology, Vol. 134, No. 5, 05.2008, p. 1470-1481.

Research output: Contribution to journalArticle

Zerbini, A, Pilli, M, Boni, C, Fisicaro, P, Penna, A, Di Vincenzo, P, Giuberti, T, Orlandini, A, Raffa, G, Pollicino, T, Raimondo, G, Ferrari, C & Missale, G 2008, 'The Characteristics of the Cell-Mediated Immune Response Identify Different Profiles of Occult Hepatitis B Virus Infection', Gastroenterology, vol. 134, no. 5, pp. 1470-1481. https://doi.org/10.1053/j.gastro.2008.02.017
Zerbini, Alessandro ; Pilli, Massimo ; Boni, Carolina ; Fisicaro, Paola ; Penna, Amalia ; Di Vincenzo, Paola ; Giuberti, Tiziana ; Orlandini, Alessandra ; Raffa, Giuseppina ; Pollicino, Teresa ; Raimondo, Giovanni ; Ferrari, Carlo ; Missale, Gabriele. / The Characteristics of the Cell-Mediated Immune Response Identify Different Profiles of Occult Hepatitis B Virus Infection. In: Gastroenterology. 2008 ; Vol. 134, No. 5. pp. 1470-1481.
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AU - Pilli, Massimo

AU - Boni, Carolina

AU - Fisicaro, Paola

AU - Penna, Amalia

AU - Di Vincenzo, Paola

AU - Giuberti, Tiziana

AU - Orlandini, Alessandra

AU - Raffa, Giuseppina

AU - Pollicino, Teresa

AU - Raimondo, Giovanni

AU - Ferrari, Carlo

AU - Missale, Gabriele

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N2 - Background& Aims: 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-γ 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.

AB - Background& Aims: 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-γ 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.

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