布来韦肽治疗慢性丁型病毒感染患者的疗效和安全性评估：亚里士多德初步观察研究。

IF 3.5 3区医学 Q2 VIROLOGY Viruses-Basel Pub Date : 2025-02-12 DOI:10.3390/v17020251

Luca Rinaldi, Mauro Viganò, Alessia Ciancio, Alfredo Caturano, Vincenzo Messina, Grazia Anna Niro, Nicolina Capoluongo, Alessandro Loglio, Letizia Marinaro, Aldo Marrone, Ernesto Claar, Maurizio Russello, Emanuela Ciracì, Umberto Vespasiani Gentilucci, Valeria Pace Palitti, Carlo Acierno, Clelia Cosentino, Andrea Mormone, Rosa Cotugno, Francesca Terracciani, Paolo Gallo, Maria Rita Cannavò, Valerio Rosato, Ferdinando Carlo Sasso, Chiara Petrucciello, Giulio Petronio Petronio, Giovanni Villone, Francesco Benanti, Giuseppe Cariti, Elisabetta Falbo, Marco Distefano, Rodolfo Sacco, Alessandro Perrella, Antonio Izzi

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引用次数: 0

摘要

丁型肝炎病毒（HDV）感染由于其严重程度和发展为肝硬化和肝细胞癌（HCC）的高风险，仍然是一个重大的全球健康挑战。Bulevirtide是一种新型的HDV进入抑制剂，通过阻断病毒进入肝细胞来治疗慢性丁型肝炎。本研究评估了布来韦肽在降低意大利HDV感染患者HDV RNA水平和改善肝功能方面的有效性和安全性。方法：这项多中心前瞻性试验从2023年6月至2024年6月招募了108例慢性HDV感染患者，这些患者接受了2 mg/天的布来韦肽联合治疗乙型肝炎病毒（HBV）感染的核苷/核苷酸类似物。包括任何阶段的肝纤维化或代偿性肝硬化患者。收集的数据包括人口统计学和临床特征、肝功能测试、HDV RNA水平以及基线和6个月时的不良事件。结果：54.6%的患者（n = 59）达到病毒学应答，其中36例显示无法检测到HDV RNA水平。应答者ALT水平从67.0 U/mL [IQR 44.0-116.3]降至31.5 U/mL [IQR 24.0-36.5, p = 0.001]， AST水平从66.0 U/mL [IQR 46.5-91.0]降至32.5 U/mL [IQR 28.0-38.0, p = 0.021]。中位HDV RNA从29,800 IU/mL [IQR 3100-375,000]降至0 IU/mL [IQR 0-291， p < 0.001]。没有出现显著的反应预测因子。轻度不良事件，包括瘙痒（5.6%）、注射部位反应（1.9%）和流感样综合征（0.9%），均有报道，未停药。结论：布来韦肽可有效降低HDV RNA水平，改善肝功能，且具有良好的安全性，为慢性丁型肝炎提供了一个有希望的治疗选择，需要进一步的大规模研究来证实这些发现并探索长期结果。

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Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study.

Introduction: Hepatitis D virus (HDV) infection remains a significant global health challenge due to its severity and high risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Bulevirtide, a novel HDV entry inhibitor, has shown promise in managing chronic hepatitis D by blocking viral entry into hepatocytes. This study evaluated the efficacy and safety of bulevirtide in reducing HDV RNA levels and improving liver function in a real-life cohort of Italian patients with HDV infection.

Methods: This multicenter prospective trial enrolled 108 consecutive patients with chronic HDV infection, from June 2023 to June 2024, who received 2 mg/day of bulevirtide in combination with a nucleoside/nucleotide analogue for hepatitis B virus (HBV) infection. Patients with any stage of liver fibrosis or compensated cirrhosis were included. Data collected included demographic and clinical characteristics, liver function tests, HDV RNA levels, and adverse events at baseline and 6 months.

Results: The virological response was achieved in 54.6% of patients (n = 59), with 36 demonstrating undetectable HDV RNA levels. Among responders, ALT levels decreased significantly from 67.0 U/mL [IQR 44.0-116.3] to 31.5 U/mL [IQR 24.0-36.5, p = 0.001], and AST levels from 66.0 U/mL [IQR 46.5-91.0] to 32.5 U/mL [IQR 28.0-38.0, p = 0.021]. Median HDV RNA dropped from 29,800 IU/mL [IQR 3100-375,000] to 0 IU/mL [IQR 0-291, p < 0.001]. No significant predictors of response emerged. Mild adverse events, including pruritus (5.6%) and injection-site reactions (1.9%) and flu-like syndrome (0.9) were reported, with no treatment discontinuation.

Conclusions: Bulevirtide effectively reduces HDV RNA levels and improves liver function with a favorable safety profile, offering a promising therapeutic option for chronic hepatitis D. Further large-scale studies are needed to confirm these findings and explore long-term outcomes.

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来源期刊

Viruses-Basel VIROLOGY-

CiteScore

7.30

自引率

12.80%

发文量

2445

审稿时长

1 months

期刊介绍： Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.