Quantitative HBsAg as a biomarker for disease staging in untreated chronic hepatitis B patients: a cross-sectional study

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Background and aims Chronic hepatitis B virus (HBV) infection is a major issue in North Africa, where HBeAg-negative profiles are predominant. Distinguishing between chronic infection and active chronic hepatitis using conventional markers is sometimes difficult. Our study assessed the correlation of HBsAg with viral load and liver fibrosis, as well as its performance in distinguishing the different evolving phases of chronic HBV infection. Approach and results We conducted an analytical cross-sectional study that included 90 HBeAg-negative treatment-naïve patients. All patients underwent biological assessment, HBsAg quantification, viral load, and FibroScan®. Among the 90 patients (mean age: 47.5 ± 11 years; 52.6% women), 65.6% were in the low-replicative chronic infection phase. The median viral load was 328.5 IU/mL, and the median HBsAg level was 213.5 IU/mL. A strong positive correlation was observed between HBsAg and HBV DNA levels ( r = 0.721, p < 0.001). HBsAg levels showed a weak but significant association with liver fibrosis ( p = 0.007, AUC = 0.631). The performance of HBsAg in differentiating low versus high replicative phases was excellent (AUC = 0.819; p < 0.001), with an optimal threshold of 450 IU/mL (sensitivity: 81.3%; specificity: 77.6%). In multivariate analysis, HBV DNA and AST were independently associated with disease phase, whereas qHBsAg was not an independent predictor. Conclusion Quantitative HBsAg measurement is a relevant tool for refining the stratification of untreated HBeAg-negative patients as a complementary surrogate marker. When combined with viral load, transaminases, and FibroScan®, HBsAg could contribute to optimized monitoring and better resource allocation.

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