The role of quantitative HBsAg in the natural history of e antigen-negative chronic hepatitis B: A Tunisian prospective study

Background/aims: During the natural course of Chronic Hepatitis B (CHB) infection, differentiation between inactive carrier (IC) and HBeAg negative CHB is a subject of ongoing debate. We studied the role of hepatitis B surface antigen (HBsAg) level as a means of differentiating between CHB and IC in a group of untreated chronic HBeAg-negative HBV-infected patients.
Study: A total of 115 HBeAg negative carriers were enrolled and followed up for>12 months; 78 as inactive carriers (IC), and 37 as active carriers (AC). Among ACs, patients were categorized according to the highest rate of viral load: AC1 (n=23), active carriers with persistent HBV-DNA<20,000 IU/mL; AC2 (n=14), active carriers with HBV-DNA>20,000 IU/mL.
Results: HBsAg levels were higher in AC compared to IC patients (1607 IU/ml vs. 225 IU/ml respectively, P=0.001). Among the AC group, the 23 AC1 cases had HBsAg levels significantly lower than the 14 AC2 patients (1756 IU/mL vs. 3327 IU/mL respectively; P<10^{-3}). HBsAg showed weak correlation with HBV-DNA in the whole cohort (r=0.44, P<0.01). The suggested cutoff value of HBsAg titer to differentiate between the two groups was 938 IU/mL. Combined single-point quantification of HBsAg (938 IU/mL) and HBV DNA (2000 IU/mL) identified IC with 87.2% specificity and 91.7% positive predictive value.
Conclusion: This study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for true inactive carriers requiring neither strict follow-up nor antiviral treatment.