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Exploring Predictive Factors for Bulevirtide Treatment Response in Hepatitis Delta-Positive Patients

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Title: Exploring Predictive Factors for Bulevirtide Treatment Response in Hepatitis Delta-Positive Patients
Authors: Verdiana Zulian, Leonidas Salichos, Chiara Taibi, Silvia Pauciullo, Levi Dong, Gianpiero D’Offizi, Elisa Biliotti, Alessia Rianda, Luigi Federici, Angela Bibbò, Martina De Sanctis, Fiona McPhee, Anna Rosa Garbuglia
Source: Biomedicines, Vol 13, Iss 2, p 280 (2025)
Publisher Information: MDPI AG, 2025.
Publication Year: 2025
Collection: LCC:Biology (General)
Subject Terms: HDV, bulevirtide, antiviral treatment, Anti-HBc IgG, genetic variability, Biology (General), QH301-705.5
More Details: Background: Hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis and is a significant global health challenge. Bulevirtide (BLV) is a novel therapeutic treatment that has resulted in variable response rates in HBV/HDV-coinfected patients. We evaluated clinical, virological, and polymorphic factors for the purpose of predicting BLV treatment success. Methods: Thirty HBV/HDV-coinfected patients received BLV monotherapy (2 mg/day) for 24 to 48 weeks. Baseline (BL) serum samples were collected to assess clinical parameters and virological markers (HDV RNA, HBV DNA, HBsAg, HBcrAg, anti-HBc IgG) at treatment weeks 24 (TW24) and 48 (TW48). Additionally, full-genome HDV sequencing and a phylogenetic analysis were performed. Finally, analyses of the HDAg protein sequence and HDV RNA secondary structure were conducted to evaluate potential associations with treatment response. Results: A significant reduction in HDV RNA levels was observed at TW48, with a virological response (HDV RNA undetectable or ≥2 Log decline from BL) achieved by 58% of patients. Median BL levels of anti-HBc IgG were significantly different between virological responders (39.3 COI; interquartile range [IQR] 31.6–47.1) and virological non-responders (244.7 COI; IQR 127.0–299.4) (p = 0.0001). HDV genotype 1e was predominant across the cohort, and no specific HDAg polymorphisms predicted the response. However, secondary structure analysis of HDV RNA revealed that a specific pattern of internal loops in the region 63–100 nucleotides downstream of the editing site may influence treatment response by impacting editing efficacy. Conclusions: This study revealed key factors influencing BLV efficacy in HBV/HDV coinfection. Lower baseline anti-HBc IgG levels strongly correlated with a positive virological response, suggesting that the liver’s inflammatory state affects treatment success. Additionally, the analysis of HDV RNA secondary structure in patients receiving BLV treatment revealed a higher editing efficiency in virological responders, highlighting areas for further research.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2227-9059
44929935
Relation: https://www.mdpi.com/2227-9059/13/2/280; https://doaj.org/toc/2227-9059
DOI: 10.3390/biomedicines13020280
Access URL: https://doaj.org/article/a5d6580c32c44929935cddb5bac5b01e
Accession Number: edsdoj.5d6580c32c44929935cddb5bac5b01e
Database: Directory of Open Access Journals
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  Data: Exploring Predictive Factors for Bulevirtide Treatment Response in Hepatitis Delta-Positive Patients
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  Data: <searchLink fieldCode="AR" term="%22Verdiana+Zulian%22">Verdiana Zulian</searchLink><br /><searchLink fieldCode="AR" term="%22Leonidas+Salichos%22">Leonidas Salichos</searchLink><br /><searchLink fieldCode="AR" term="%22Chiara+Taibi%22">Chiara Taibi</searchLink><br /><searchLink fieldCode="AR" term="%22Silvia+Pauciullo%22">Silvia Pauciullo</searchLink><br /><searchLink fieldCode="AR" term="%22Levi+Dong%22">Levi Dong</searchLink><br /><searchLink fieldCode="AR" term="%22Gianpiero+D%27Offizi%22">Gianpiero D’Offizi</searchLink><br /><searchLink fieldCode="AR" term="%22Elisa+Biliotti%22">Elisa Biliotti</searchLink><br /><searchLink fieldCode="AR" term="%22Alessia+Rianda%22">Alessia Rianda</searchLink><br /><searchLink fieldCode="AR" term="%22Luigi+Federici%22">Luigi Federici</searchLink><br /><searchLink fieldCode="AR" term="%22Angela+Bibbò%22">Angela Bibbò</searchLink><br /><searchLink fieldCode="AR" term="%22Martina+De+Sanctis%22">Martina De Sanctis</searchLink><br /><searchLink fieldCode="AR" term="%22Fiona+McPhee%22">Fiona McPhee</searchLink><br /><searchLink fieldCode="AR" term="%22Anna+Rosa+Garbuglia%22">Anna Rosa Garbuglia</searchLink>
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  Data: Biomedicines, Vol 13, Iss 2, p 280 (2025)
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  Data: <searchLink fieldCode="DE" term="%22HDV%22">HDV</searchLink><br /><searchLink fieldCode="DE" term="%22bulevirtide%22">bulevirtide</searchLink><br /><searchLink fieldCode="DE" term="%22antiviral+treatment%22">antiviral treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Anti-HBc+IgG%22">Anti-HBc IgG</searchLink><br /><searchLink fieldCode="DE" term="%22genetic+variability%22">genetic variability</searchLink><br /><searchLink fieldCode="DE" term="%22Biology+%28General%29%22">Biology (General)</searchLink><br /><searchLink fieldCode="DE" term="%22QH301-705%2E5%22">QH301-705.5</searchLink>
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  Data: Background: Hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis and is a significant global health challenge. Bulevirtide (BLV) is a novel therapeutic treatment that has resulted in variable response rates in HBV/HDV-coinfected patients. We evaluated clinical, virological, and polymorphic factors for the purpose of predicting BLV treatment success. Methods: Thirty HBV/HDV-coinfected patients received BLV monotherapy (2 mg/day) for 24 to 48 weeks. Baseline (BL) serum samples were collected to assess clinical parameters and virological markers (HDV RNA, HBV DNA, HBsAg, HBcrAg, anti-HBc IgG) at treatment weeks 24 (TW24) and 48 (TW48). Additionally, full-genome HDV sequencing and a phylogenetic analysis were performed. Finally, analyses of the HDAg protein sequence and HDV RNA secondary structure were conducted to evaluate potential associations with treatment response. Results: A significant reduction in HDV RNA levels was observed at TW48, with a virological response (HDV RNA undetectable or ≥2 Log decline from BL) achieved by 58% of patients. Median BL levels of anti-HBc IgG were significantly different between virological responders (39.3 COI; interquartile range [IQR] 31.6–47.1) and virological non-responders (244.7 COI; IQR 127.0–299.4) (p = 0.0001). HDV genotype 1e was predominant across the cohort, and no specific HDAg polymorphisms predicted the response. However, secondary structure analysis of HDV RNA revealed that a specific pattern of internal loops in the region 63–100 nucleotides downstream of the editing site may influence treatment response by impacting editing efficacy. Conclusions: This study revealed key factors influencing BLV efficacy in HBV/HDV coinfection. Lower baseline anti-HBc IgG levels strongly correlated with a positive virological response, suggesting that the liver’s inflammatory state affects treatment success. Additionally, the analysis of HDV RNA secondary structure in patients receiving BLV treatment revealed a higher editing efficiency in virological responders, highlighting areas for further research.
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