Exploring Predictive Factors for Bulevirtide Treatment Response in Hepatitis Delta-Positive Patients
| Title: | Exploring Predictive Factors for Bulevirtide Treatment Response in Hepatitis Delta-Positive Patients |
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| 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 |
| ISSN: | 22279059 44929935 |
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| DOI: | 10.3390/biomedicines13020280 |
| Published in: | Biomedicines |
| Language: | English |