title: Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease.
abstract: Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Liu-Wei
authors.initials: LW
authors.lastname: Song
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cavallone
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Moriconi
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cherubini
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Colombatto
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Oliveri
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Barbara Agata
authors.initials: BA
authors.lastname: Coco
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ricco
authors.affiliation: Digestive and Liver Disease, General Medicine II Unit, University Hospital of Pisa, Pisa, Italy.
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: James Wai Kuo
authors.initials: JW
authors.lastname: Shih
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
authors.affiliation: Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
authors.forename: Maurizia Rossana
authors.initials: MR
authors.lastname: Brunetto
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D002353:Carrier State; D005260:Female; D006509:Hepatitis B / Q000097:blood* / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood* / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens