Improving Virological Monitoring of HDV Infection: A Proof-of-Concept Comparative Study of Bosphore and AltoStar® Assays in Patients Treated with Bulevirtide.

Hepatitis delta virus (HDV) infection is associated with severe hepatic complications and rapid progression towards liver cirrhosis and hepatocellular carcinoma. Accurate measurement of HDV RNA is critical for monitoring therapeutic responses, especially during treatment with novel therapies such as bulevirtide (BLV). This study compared the analytical performance of two HDV RNA quantification assays, Bosphore (Anatolia) and AltoStar® (Altona), focusing on their sensitivity, specificity, and potential implications for clinical management. Sixty-one clinical samples from twenty-four patients, including fifteen HDV-infected patients receiving BLV treatment and nine controls, were tested using each assay. Of 30 samples identified as HDV-negative by the Bosphore assay, 17 (56.7%) were HDV-positive with AltoStar®, demonstrating the superior sensitivity (p < 0.0001) of the latter assay. Quantitative analyses revealed consistently higher viral load measurements with AltoStar® compared to Bosphore, with a difference of 1.23 Log IU/mL and a moderate correlation (r2 = 0.7385) between assays. Each assay demonstrated a high specificity, with no false positives detected among control samples. However, our findings suggest that differences in assay sensitivity could impact the evaluation of virological response, highlighting the risk of false-negative results in chronically HDV-infected patients with low-level viremia. This emphasizes the need for careful assay selection to accurately monitor treatment outcomes.