The Characteristics of the Cell-Mediated Immune Response Identify Different Profiles of Occult Hepat

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Gastroenterology. 2008 Feb 14 [Epub ahead of print]

The Characteristics of the Cell-Mediated Immune Response Identify Different

Profiles of Occult Hepatitis B Virus Infection.

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.

Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma,

Parma, Italy.

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-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.

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