1. Volume 134, Issue 5, Pages 1470-1481 (May 2008)
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 
Gastroenterology 
Volume 134, Issue 5, Pages (May 2008)
DOI: /j.gastro
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2. Figure 1
Ex vivo IFN-γ ELISPOT responses to individual HBV antigens in patients with and without occult HBV infection. (A) ELISPOT results obtained in the different patient populations are illustrated according to responses obtained by stimulation with HBV peptides spanning individual HBV regions (x, core, envelope, polymerase) and with recombinant envelope antigens corresponding to preS1, preS2, and S regions. (B) Comparisons of mean spots of the positive tests and frequency of positive responses (calculated on all tests) obtained in the different patients’ groups are presented: □, HBV-DNA positive and anti-HBc negative; ■, HBV-DNA positive and anti-HBc positive; □, HBV-DNA negative and anti-HBc positive; , CH-C.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions

3. Figure 2
Intensity of the HBV-specific CD4- and CD8-mediated T-cell reactivity. After 10 days of in vitro stimulation with the same peptide pools used for ex vivo analysis, expanded T cells were tested in a culture IFN-γ ELISPOT assay. Tests showing at least 1.5-fold the number of spot-forming colonies obtained with medium were confirmed by IFN-γ intracellular staining (rate of confirmation of the positive ELISPOT results ranging from 75% to 82% in the different patients' groups). (A) Mean IFN-γ production induced by HBV peptides is illustrated for patients with occult HBV infection negative or positive for anti-HBc, for patients positive for anti-HBc and negative for intrahepatic HBV-DNA, for HBsAg-inactive carriers, for anti-HBe–positive CH-B patients, and for CH-C patients negative for HBV serum markers and intrahepatic HBV DNA. Each bar in the upper part of A represents the mean percentage ± standard error of IFN-γ–positive CD4+ and CD8+ cells reactive to all peptide mixtures representing each HBV antigen. Comparisons of mean frequencies of IFN-γ–positive CD4 and CD8 cells and frequencies of positive responses obtained in the different patient groups to all peptide pools is presented at the bottom. ■, CD8+; □, CD4+. (B) The sum of the frequencies of tetramer-positive CD8 cells measured ex vivo and after in vitro expansion in HLA-A2–positive patients is presented. Seven patients with occult HBV infection (4 anti-HBc–negative and 3 anti-HBc–positive patients), 2 anti-HBc–positive patients with undetectable intrahepatic HBV DNA, and 2 HBsAg-inactive carriers were studied. □, Ex vivo; , T-cell line.
Gastroenterology  , DOI: ( /j.gastro )
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4. Figure 3
Phenotypic and functional profiles of tetramer-positive CD8 cells. Top panels illustrate percentages of HBV tetramer-positive CD8 lymphocytes with different specificities, analyzed ex vivo and after 10 days in vitro expansion in representative HBsAg-negative patients with and without occult HBV infection and in a HBsAg-inactive carrier. Lower panels illustrate the phenotypic and functional analysis of 3 representative patients (patient 18, occult+ anti-HBc+; patient 23, occult- anti-HBc+; patient 28, HBsAg+-inactive carrier). CD127, PD1, CCR7, perforin, and granzyme-B were tested ex vivo, whereas intracellular IFN-γ and IL-2 expression as well as CD107a were tested after in vitro expansion.
Gastroenterology  , DOI: ( /j.gastro )
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5. Figure 4
Sequencing of the entire preC-C genomic region in patients with occult HBV infection. Sequencing was performed in 3 anti-HBc–negative (patients 1, 3, and 7) and 4 anti-HBc–positive patients (patients 12, 13, 15, and 16). HBV sequences derived from 6 patients were aligned to a representative genotype D (GenBank accession number: V01460),19 whereas the HBV sequence derived from patient 12 was aligned to a representative genotype A (GenBank accession number: X02763).27 The number of variations over the 212 aligned amino acid residues is shown in parentheses for each patient.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions