title: Long-term outcome of inactive and active, low viraemic HBeAg-negative-hepatitis B virus infection: Benign course towards HBsAg clearance.
abstract: The difference between the long-term outcome of low-viraemic (HBV-DNA≤20 000-IU/mL, LV-AC) and inactive HBsAg carriers (HBV-DNA≤2000-IU/mL, IC) remains to be defined. We studied prospectively 153 HBeAg-negative HBsAg-carriers with baseline HBV-DNA≤20 000-IU/mL and normal transaminases.
  
  
  
  IC, LV-AC or chronic hepatitis B (CHB) (HBV-DNA persistently ≤2000-IU/mL, ≤20 000-IU/mL or >20 000-IU/mL respectively) were diagnosed after 1-year, 3-monthly monitoring. Thereafter IC and LV-AC were followed-up for additional 57.2 (8.5-158.3) months. HBV-DNA, HBsAg, HBV"core-related"Antigen (HBcrAg) and total-anti-HBc were quantified at baseline.
  
  
  
  After the 1st year diagnostic follow-up CHB [higher HBV-DNA (P=.005), total-anti-HBc (P=.012), ALT (P=.007) and liver-stiffness (P=.021)] was identified in 20 (13.1%) carriers; baseline HBsAg≤1000IU/HBV-DNA≤2000IU/mL excluded the presence of CHB (NPV-100%). Thereafter, during the long-term follow-up none of 87 IC reactivated, 19 (21.8%) cleared HBsAg [older-age (P=.004), lower HBsAg (P<.001), higher yearly HBsAg decline (P<.001)]. Twenty-five of 46 (54.3%) LV-AC remained stable, 20 (43.5%) became IC and 1 (2.2%) developed CHB. The best single-point CHB and IC diagnostic-accuracies were total-anti-HBc (84.2%, NPV-98.2%) and HBV-DNA/total-anti-HBc/HBcrAg combination (89.5%, 93%-sensitivity, 84.8%-specificity) respectively.
  
  
  
  Viraemia persistently ≤20 000-IU/mL predicts a benign clinical outcome: it was associated with transition to IC in 43% of LV-AC and to Occult HBV Infection in 20% of IC within 5-years. Nevertheless, 13.1% of individuals with low viraemia at presentation develops CHB within 1 year: 1-year HBV-DNA monitoring resulted the most accurate diagnostic approach that can be limited to at least a half of cases by the single point HBV-DNA/HBsAg quantification. The IC-diagnostic-accuracy combining HBV-DNA/total-anti-HBc/HBcrAg needs to be confirmed in further studies.
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Filippo
authors.identifier: 0000-0002-9794-7203
authors.initials: F
authors.lastname: Oliveri
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Surace
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cavallone
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Colombatto
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ricco
authors.affiliation: Department of Economics and Management, University of Pisa, Pisa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvati
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Coco
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Romagnoli
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gattai
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvati
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Moriconi
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health and School of Life Science, Xiamen University, Xiamen, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: University of Pittsburgh Medical Center Institute for Health, Chianciano-Terme and Fondazione Italiana Fegato, AREA Science Park, Trieste, Italy.
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
authors.affiliation: Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.|Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Maurizia R
authors.initials: MR
authors.lastname: Brunetto
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002353:Carrier State / Q000097:blood / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014766:Viremia / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase
keywords: HBeAg negative CHB; HBsAg clearance; inactive infection; quantitative HBsAg