HBsAg Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D

• DOI: 10.1111/liv.70094
• Publication Date: 2025-04-28T09:54:13Z
• Authors: Stefano D'Anna; Romina Salpini; Elisabetta Degasperi; Lorenzo Piermatteo; Floriana Facchetti; Dana Sambarino; Giulia Torre; Marta Borghi; Maria Paola Anolli; Sara Monico; Valentina Svicher; Pietro Lampertico
• Keywords: Hepatitis D virus; Hepatitis B

ABSTRACT Background and Aims HDV exploits HBV surface‐protein (HBsAg) for entering into hepatocytes. HBsAg consists of 3 isoforms: Large‐ (L‐HBs, predominantly present in virions mediating binding to NTCP‐receptor), Middle‐ (M‐HBs) Small‐HBsAg (S‐HBs). Here, we investigated the kinetics HBs isoforms under bulevirtide treatment (BLV). Methods 67 consecutive patients with HDV‐related compensated cirrhosis starting BLV 2 mg/day were enrolled. L‐HBs, M‐HBs S‐HBs quantified by ad‐hoc ELISAs baseline week 48 (W48) samples. Results At baseline, median (IQR) HDV‐RNA was 5.1 (4.3–5.7) log IU/mL while S‐HBs, L‐HBs levels 3801 (1401–7462), 743 (211–1710) 5 (1–13) ng/mL. W48, virological responses (VR) observed 72% (48/67) patients, 25.4% (17/67) achieved undetectable (11/17 ALT‐normalisation). A decline 51%, 63% 31% (median [IQR] decline: 961 [461–1985], 258 [68–626] 4 [2‐12] ng/mL). Notably, at W48 had lower than not achieving this end‐point (1 [0.3–7] vs. 6 [2‐13] ng/mL, p = 0.04 1570 [369–5185] 4015 [1646–8687] 0.002). By AUROC, < ng/mL or 3400 more likely achieve undetectability (39.3% 15.8%, 38.7% 13.9%, 0.03). Furthermore, combination pre‐treatment + 5logIU/mL best predictor (56.3% 15.7%, 0.002 60% 11%, 0.001). Conclusions Quantification along HDV‐RNA, may reflect burden circulating infectious HBV/HDV co‐infection, providing a promising tool identify respond BLV.