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 and mediating binding to NTCP-receptor), Middle- (M-HBs) and Small-HBsAg (S-HBs). Here, we investigated the kinetics of 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 and S-HBs were quantified by ad-hoc ELISAs in baseline and week 48 (W48) samples. Results: At baseline, median (IQR) HDV-RNA was 5.1 (4.3–5.7) log IU/mL while median (IQR) S-HBs, M-HBs and L-HBs levels were 3801 (1401–7462), 743 (211–1710) and 5 (1–13) ng/mL. At W48, virological responses (VR) were observed in 72% (48/67) of patients, while 25.4% (17/67) achieved undetectable HDV-RNA (11/17 with ALT-normalisation). A decline of S-HBs, M-HBs and L-HBs levels was observed in 51%, 63% and 31% of patients (median [IQR] decline: 961 [461–1985], 258 [68–626] and 4 [2-12] ng/mL). Notably, patients with undetectable HDV-RNA at W48 had baseline L-HBs and S-HBs levels lower than patients not achieving this end-point (1 [0.3–7] vs. 6 [2-13] ng/mL, p = 0.04 and 1570 [369–5185] vs. 4015 [1646–8687] ng/mL, p = 0.002). By AUROC, patients with baseline L-HBs < 3 ng/mL or S-HBs < 3400 ng/mL were more likely to achieve HDV-RNA undetectability at W48 (39.3% vs. 15.8%, p = 0.04 and 38.7% vs. 13.9%, p = 0.03). Furthermore, the combination of pre-treatment L-HBs < 3 ng/mL + HDV-RNA < 5logIU/mL and S-HBs < 3400 ng/mL + HDV-RNA < 5logIU/mL was the best predictor for achieving undetectable HDV-RNA at W48 (56.3% vs. 15.7%, p = 0.002 and 60% vs. 11%, p < 0.001). Conclusions: Quantification of L-HBs and of S-HBs, along with HDV-RNA, may reflect the burden of circulating infectious virions in HBV/HDV co-infection, providing a promising tool to identify patients more likely to respond to BLV.
D'Anna, S., Salpini, R., Degasperi, E., Piermatteo, L., Facchetti, F., Sambarino, D., et al. (2025). HBsAg Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D. LIVER INTERNATIONAL, 45(5) [10.1111/liv.70094].
HBsAg Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D
D'Anna, Stefano;Salpini, Romina;Piermatteo, Lorenzo;Torre, Giulia;Svicher, Valentina
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2025-05-01
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 and mediating binding to NTCP-receptor), Middle- (M-HBs) and Small-HBsAg (S-HBs). Here, we investigated the kinetics of 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 and S-HBs were quantified by ad-hoc ELISAs in baseline and week 48 (W48) samples. Results: At baseline, median (IQR) HDV-RNA was 5.1 (4.3–5.7) log IU/mL while median (IQR) S-HBs, M-HBs and L-HBs levels were 3801 (1401–7462), 743 (211–1710) and 5 (1–13) ng/mL. At W48, virological responses (VR) were observed in 72% (48/67) of patients, while 25.4% (17/67) achieved undetectable HDV-RNA (11/17 with ALT-normalisation). A decline of S-HBs, M-HBs and L-HBs levels was observed in 51%, 63% and 31% of patients (median [IQR] decline: 961 [461–1985], 258 [68–626] and 4 [2-12] ng/mL). Notably, patients with undetectable HDV-RNA at W48 had baseline L-HBs and S-HBs levels lower than patients not achieving this end-point (1 [0.3–7] vs. 6 [2-13] ng/mL, p = 0.04 and 1570 [369–5185] vs. 4015 [1646–8687] ng/mL, p = 0.002). By AUROC, patients with baseline L-HBs < 3 ng/mL or S-HBs < 3400 ng/mL were more likely to achieve HDV-RNA undetectability at W48 (39.3% vs. 15.8%, p = 0.04 and 38.7% vs. 13.9%, p = 0.03). Furthermore, the combination of pre-treatment L-HBs < 3 ng/mL + HDV-RNA < 5logIU/mL and S-HBs < 3400 ng/mL + HDV-RNA < 5logIU/mL was the best predictor for achieving undetectable HDV-RNA at W48 (56.3% vs. 15.7%, p = 0.002 and 60% vs. 11%, p < 0.001). Conclusions: Quantification of L-HBs and of S-HBs, along with HDV-RNA, may reflect the burden of circulating infectious virions in HBV/HDV co-infection, providing a promising tool to identify patients more likely to respond to BLV.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
