Editorial: Beyond Positive or Negative—Unlocking Semi-Quantitative Information From a Rapid HBsAg Test

Abstract

Chronic hepatitis B (CHB) remains a major public health challenge, disproportionately affecting low and middle-income countries [1]. Although effective antiviral therapy is available, identifying individuals who require treatment remains challenging in many resource-constrained settings because assessment of viral replication, liver inflammation and fibrosis relies on laboratory tests that are often inaccessible because of cost, centralized laboratory infrastructure and limited availability [2]. Field-adapted alternatives are beginning to emerge, including a hepatitis B core-related antigen rapid diagnostic test (HBcrAg-RDT) developed to identify individuals with high HBV DNA levels at the point of care [3]. Quantitative hepatitis B surface antigen (qHBsAg) provides complementary information for characterizing the phase of CHB infection, but its measurement also requires dedicated laboratory platforms rarely available in resource-limited settings [4]. Asmamaw and colleagues investigate whether measuring the time-to-positivity of a rapid HBsAg test can serve as a practical surrogate for qHBsAg [5].

Using prospectively collected samples from Spain and Ethiopia, the investigators evaluated the relationship between the time-to-positivity of a commercially available rapid HBsAg test and HBsAg concentrations quantified by chemiluminescent immunoassay. In each cohort, an optimal time-to-positivity threshold for identifying samples with qHBsAg below 1000 IU/mL was selected separately using receiver operating characteristic curve analysis and Youden's index. In Spain, a threshold of 2.37 min yielded a sensitivity of 68.2% and specificity of 91.4%. In Ethiopia, the corresponding threshold was shorter, at 1.61 min, and showed a sensitivity of 64.3% and specificity of 60.0%. These findings provide proof of concept that a conventional rapid HBsAg test may provide clinically relevant semi-quantitative information beyond the binary detection of HBsAg.

The substantial difference in optimal time-to-positivity thresholds between the Spanish and Ethiopian cohorts for distinguishing HBsAg concentrations above or below 1000 IU/mL suggests that a single universal cut-off may not be applicable across settings. Before widespread use, the optimal threshold may therefore need to be established and validated in each intended population and context, potentially limiting the simplicity and scalability of the approach. Operational feasibility also warrants careful consideration. Measuring time to positivity requires a reader to remain beside the test and continuously observe it from sample application until the test line appears, which may take several minutes and prevent the reader from attending to other tasks. Digital readers may eventually reduce the need for continuous human observation, but their feasibility, cost, and performance require evaluation under routine conditions.

Time-to-positivity offers an innovative opportunity to extract clinically informative, semi-quantitative data from a familiar and widely available diagnostic test. With further validation across diverse populations, standardized reading procedures and integration into practical clinical pathways, this simple approach could contribute to more accessible and decentralized assessment of chronic hepatitis B in resource-limited settings.

Rewhandamzi Boms: writing – original draft, writing – review and editing. Yusuke Shimakawa: writing – review and editing.

The authors have nothing to report.

This article is linked to Asmamaw et al. papers. To view this article, visit https://doi.org/10.1111/apt.70892.

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.