Hepatitis B core-related antigen rapid diagnostic test for point-of-care identification of women at high risk of hepatitis B vertical transmission: a multicountry diagnostic accuracy study

Abstract

Background: Timely administration of the hepatitis B virus (HBV) birth dose vaccine, along with identifying high-risk pregnant individuals for antiviral prophylaxis, is essential for the global elimination of vertical transmission of HBV. However, in resource-limited settings, access to HBV DNA testing is scarce, and accurate rapid tests for HBeAg are lacking. We aimed to assess the diagnostic performance of a newly developed hepatitis B core-related antigen (HBcrAg) rapid diagnostic test (RDT) to identify women who are HBsAg-positive and eligible for antiviral prophylaxis.

Methods: In this multicountry diagnostic accuracy study, we retrospectively validated the HBcrAg-RDT using stored plasma from pregnant women who were HBsAg-positive in cohort studies from Cambodia and Cameroon and prospectively using finger-prick capillary blood from postpartum mothers at rural health centres in Burkina Faso. We estimated the sensitivity and specificity of the HBcrAg-RDT for diagnosing high HBV DNA concentrations (≥200 000 IU/mL) using real-time PCR (rtPCR) as the reference. We compared the diagnostic performance of the HBcrAg-RDT with that of conventional HBeAg assays based on the area under the receiver operating characteristic curve (AUROC).

Findings: In total, plasma samples were available for 1964 participants: 1194 stored plasma samples available for analysis from the Cambodian cohort, 501 stored samples from the Cameroonian cohort, and 269 prospectively collected samples from women in the Burkina Faso cohort. In the pooled population, the mean age was 28·1 years (SD 6·0), and 382 (20·0%) were HBeAg positive. The HBcrAg-RDT showed an overall sensitivity of 93·1% (95% CI 90·5-95·2) and specificity of 94·3% (93·0-95·4). Sensitivity and specificity were 93·4% (90·7-95·5) and 94·4% (92·9-95·6) in the retrospective laboratory-based analyses of samples from Cambodia and Cameroon, and 89·7% (75·8-97·1) and 93·9% (90·0-96·6) in the prospective real-world analysis of samples of HBsAg-positive women from Burkina Faso. The AUROC for HBcrAg-RDT (0·937 [95% CI 0·924-0·950]) in distinguishing high versus low HBV DNA concentrations at the 200 000 IU/mL threshold in the pooled data set was significantly higher than that of HBeAg rapid tests (0·822 [0·798-0·845]; p<0·0001) and similar to laboratory-based HBeAg immunoassays (ELISA and chemiluminescence assay; 0·926 [0·897-0·955]; p=0·72). In Burkina Faso, the median turnaround time for HBV DNA testing was 46 days (IQR 31-72), whereas HBcrAg-RDT provided same-day results for all participants.

Interpretation: HBcrAg-RDT might offer a practical solution for integrating the prevention of vertical transmission of HBV into decentralised antenatal care in resource-limited settings, enabling timely identification and management of pregnant individuals who are at high risk of transmission.

Funding: Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Total Foundation, Gilead Sciences, and Japan Society for the Promotion of Science.

Translation: For the French translation of the abstract see Supplementary Materials section.