The accurate identification of inactive (serum HBV-DNA persistently ≤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.

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.

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 ≥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 (≤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.

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.