title: Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective.
abstract: OBJECTIVE
  The quantifiable level of HBsAg has been suggested as a predictor of treatment response in chronic hepatitis B. However, there is limited information on HBsAg levels considering the dynamic natural course of HBV-infection. This study aimed to determine HBsAg levels in the different phases of HBV-infection in European HBsAg-positive patients.
  
  
  METHODS
  226 HBV-monoinfected patients, not undergoing antiviral therapy, were analyzed in a cross-sectional study. Patients were categorized according to the phase of HBV-infection: HBeAg(+) immune tolerance phase (IT, n=30), immune clearance phase (IC, n=48), HBeAg(-) low-replicative phase (LR, n=68), HBeAg(-) hepatitis (ENH, n=68), and acute hepatitis B (n=12). HBsAg was quantified and correlated with HBV-DNA, HBV-genotypes and clinical parameters. In addition, 30 LR-patients were followed longitudinally.
  
  
  RESULTS
  HBsAg levels were higher in IT-patients and IC-patients compared to LR-patients and ENH-patients (4.96/4.37/3.09/3.87-log(10)IU/ml, p<0.001). HBsAg showed a strong correlation with HBV-DNA during acute hepatitis B (R=0.79, p<0.01). Correlation of HBsAg and HBV-DNA was weak or missing when analyzing different phases of persistent HBV-infection separately. However, associations between HBsAg and HBV-DNA were observed in patients infected with HBV-genotype D but not with HBV-genotype A. LR-patients with HBV-reactivation during follow-up (increase of HBV-DNA >2000IU/ml) showed >3-fold higher baseline HBsAg levels with a NPV of 95% for an HBsAg cut-off of 3500IU/ml.
  
  
  CONCLUSIONS
  HBsAg levels show significant differences during the natural course of HBV-infection and between HBV-genotypes. These findings may have important implications for understanding the natural history of HBV-infection and for using quantitative HBsAg as a diagnostic tool, i.e. as a marker for predicting HBV-reactivation.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, Hannover, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jaroszewicz
authors.forename: Beatriz
authors.initials: B
authors.lastname: Calle Serrano
authors.forename: Karsten
authors.initials: K
authors.lastname: Wursthorn
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.forename: Jerome
authors.initials: J
authors.lastname: Schlue
authors.forename: Regina
authors.initials: R
authors.lastname: Raupach
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: C-Thomas
authors.initials: CT
authors.lastname: Bock
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000378:metabolism; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006509:Hepatitis B / Q000097:blood* / Q000276:immunology / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens