The characteristics of the cell-mediated immune response identify different profiles of occult hepatitis B virus infection

被引:122
作者
Zerbini, Alessandro [1 ]
Pilli, Massimo [1 ]
Boni, Carolina [1 ]
Fisicaro, Paola [1 ]
Penna, Amalia [1 ]
Di Vincenzo, Paola [1 ]
Giuberti, Tiziana [1 ]
Orlandini, Alessandra [1 ]
Raffa, Giuseppina [2 ]
Pollicino, Teresa [2 ]
Raimondo, Giovanni [2 ]
Ferrari, Carlo [1 ]
Missale, Gabriele [1 ]
机构
[1] Univ Parma, Azienda Osped, Lab Viral Immunopathol, I-43100 Parma, Italy
[2] Univ Messina, Dept Internal Med, Lab Mol Biol & Hepatol, I-98100 Messina, Italy
关键词
D O I
10.1053/j.gastro.2008.02.017
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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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页码:1470 / 1481
页数:12
相关论文
共 30 条
[21]   The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response [J].
Rehermann, B ;
Ferrari, C ;
Pasquinelli, C ;
Chisari, FV .
NATURE MEDICINE, 1996, 2 (10) :1104-1108
[22]   Isolated anti-HBc in chronic hepatitis C predicts a poor response to interferon treatment [J].
Sagnelli, E ;
Coppola, N ;
Scolastico, C ;
Mogavero, AR ;
Stanzione, M ;
Filippini, P ;
Felaco, FM ;
Piccinino, F .
JOURNAL OF MEDICAL VIROLOGY, 2001, 65 (04) :681-687
[23]   Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein [J].
Schüttler, CG ;
Fiedler, N ;
Schmidt, K ;
Repp, R ;
Gerlich, WH ;
Schaefer, S .
JOURNAL OF HEPATOLOGY, 2002, 37 (06) :855-862
[24]   SUPPRESSION OF HEPATITIS-B VIRUS EXPRESSION AND REPLICATION BY HEPATITIS-C VIRUS CORE PROTEIN IN HUH-7 CELLS [J].
SHIH, CM ;
LO, SCJ ;
MIYAMURA, T ;
CHEN, SY ;
LEE, YHW .
JOURNAL OF VIROLOGY, 1993, 67 (10) :5823-5832
[25]   Human cytomegalovirus latency and reactivation -: A delicate balance between the virus and its host's immune system [J].
Söderberg-Nauclér, C ;
Nelson, JA .
INTERVIROLOGY, 1999, 42 (5-6) :314-321
[26]  
THIERS V, 1988, LANCET, V2, P1273
[27]   Occult hepatitis B [J].
Torbenson, M ;
Thomas, DL .
LANCET INFECTIOUS DISEASES, 2002, 2 (08) :479-486
[28]  
VALENZUELA P, 1980, ANIMAL VIRUS GENETIC, P57
[29]   Memory CD8 T-cell differentiation during viral infection [J].
Wherry, EJ ;
Ahmed, R .
JOURNAL OF VIROLOGY, 2004, 78 (11) :5535-5545
[30]   New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA [J].
Zoulim, F .
JOURNAL OF HEPATOLOGY, 2005, 42 (03) :302-308