title: Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers.
abstract: OBJECTIVE
  The accurate identification of inactive (serum HBV-DNA persistently <or=2000 IU/mL) hepatitis B virus (HBV) carriers (IC) is difficult because of wide and frequent HBV-DNA fluctuations. We studied whether hepatitis B surface antigen (HBsAg) serum levels (HBsAgsl) quantification may contribute to diagnosis of HBV phases in untreated hepatitis B e antigen-negative genotype D asymptomatic carriers.
  
  
  METHODS
  HBsAgsl were measured at baseline and end of follow-up and correlated with virologic and biochemical profiles of 209 consecutive carriers followed-up prospectively (median, 29; range, 12-110 months). HBV phases were defined after 1-year monthly monitoring of HBV-DNA and transaminases.
  
  
  RESULTS
  HBsAgsl were significantly lower in 56 inactive carriers (IC) than 153 active carriers (AC): median, 62.12 (range, 0.1-4068) vs median, 3029 (range, 0.5-82,480) IU/mL; P<.001. Among AC, HBsAgsl were lower in 31 AC whose viremia remained persistently <20,000 IU/mL (AC1) than in 122 AC with fluctuations>or=20,000 IU/mL (AC2): 883 (0.5-7838) vs 4233 (164-82,480) IU/mL, P=.002. HBV infection was less productive in IC and AC1 than AC2 (log10 HBV-DNA/HBsAgsl ratios 0.25 and 0.49 vs 2.06, respectively, P<.001) and in chronic hepatitis than cirrhosis (1.97 vs 2.34, respectively; P=.023). The combined single point quantification of HBsAg (<1000 IU/mL) and HBV-DNA (<or=2000 IU/mL) identified IC with 94.3% diagnostic accuracy, 91.1% sensitivity, 95.4% specificity, 87.9% positive predictive value, 96.7% negative predictive value. During follow-up, HBsAgsl were stable in AC but declined in IC (yearly median decline, -0.0120 vs -0.0768 log10 IU/mL, respectively, P<.001), 10 of whom cleared HBsAg.
  
  
  CONCLUSIONS
  HBsAgsl vary during chronic hepatitis B e antigen-negative genotype D infection and are significantly lower in IC. Single-point combined HBsAg and HBV-DNA quantification provides the most accurate identification of IC, comparable with that of long-term tight monitoring.
authors.affiliation: Hepatology Unit, University Hospital of Pisa, University of Pisa, Pisa, Italy. brunetto@med-club.com
authors.forename: Maurizia Rossana
authors.initials: MR
authors.lastname: Brunetto
authors.forename: Filippo
authors.initials: F
authors.lastname: Oliveri
authors.forename: Piero
authors.initials: P
authors.lastname: Colombatto
authors.forename: Francesco
authors.initials: F
authors.lastname: Moriconi
authors.forename: Pietro
authors.initials: P
authors.lastname: Ciccorossi
authors.forename: Barbara
authors.initials: B
authors.lastname: Coco
authors.forename: Veronica
authors.initials: V
authors.lastname: Romagnoli
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cherubini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Moscato
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Maina
authors.forename: Daniela
authors.initials: D
authors.lastname: Cavallone
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002353:Carrier State; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D013997:Time Factors; D014775:Virus Activation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens