Hepatitis B Surface Antigen Serum Levels Help to Distinguish Active From Inactive Hepatitis B Virus Genotype D Carriers

Gastroenterology. 2010 Aug;139(2):483-90. doi: 10.1053/j.gastro.2010.04.052. Epub 2010 May 5.


Background & aims: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Carrier State*
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / diagnosis*
  • Hepatitis B, Chronic / epidemiology
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Prospective Studies
  • Sensitivity and Specificity
  • Serologic Tests
  • Time Factors
  • Virus Activation*
  • Young Adult


  • Biomarkers
  • DNA, Viral
  • Hepatitis B Surface Antigens