慢性丁型肝炎病毒感染患者接受布来维亭治疗的疗效与安全性评估：亚里士多德先导性观察研究
Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study.
作者信息
Rinaldi Luca, Viganò Mauro, Ciancio Alessia, Caturano Alfredo, Messina Vincenzo, Niro Grazia Anna, Capoluongo Nicolina, Loglio Alessandro, Marinaro Letizia, Marrone Aldo, Claar Ernesto, Russello Maurizio, Ciracì Emanuela, Gentilucci Umberto Vespasiani, Pace Palitti Valeria, Acierno Carlo, Cosentino Clelia, Mormone Andrea, Cotugno Rosa, Terracciani Francesca, Gallo Paolo, Cannavò Maria Rita, Rosato Valerio, Sasso Ferdinando Carlo, Petrucciello Chiara, Petronio Petronio Giulio, Villone Giovanni, Benanti Francesco, Cariti Giuseppe, Falbo Elisabetta, Distefano Marco, Sacco Rodolfo, Perrella Alessandro, Izzi Antonio
机构信息
Department of Medicine and Health Sciences "Vincenzo Tiberio", Università degli Studi del Molise, 86100 Campobasso, Italy.
Gastroenterology, Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy.
出版信息
Viruses. 2025 Feb 12;17(2):251. doi: 10.3390/v17020251.
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 ( = 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, = 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, = 0.021]. Median HDV RNA dropped from 29,800 IU/mL [IQR 3100-375,000] to 0 IU/mL [IQR 0-291, < 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.
引言
由于丁型肝炎病毒（HDV）感染的严重性以及进展为肝硬化和肝细胞癌（HCC）的高风险，它仍然是一项重大的全球健康挑战。新型HDV进入抑制剂布列韦肽已显示出通过阻断病毒进入肝细胞来治疗慢性丁型肝炎的前景。本研究评估了布列韦肽在降低意大利HDV感染患者真实队列中HDV RNA水平和改善肝功能方面的疗效和安全性。
方法
这项多中心前瞻性试验纳入了2023年6月至2024年6月期间连续的108例慢性HDV感染患者，他们接受2mg/天的布列韦肽联合核苷/核苷酸类似物治疗乙型肝炎病毒（HBV）感染。纳入了任何肝纤维化阶段或代偿期肝硬化患者。收集的数据包括人口统计学和临床特征、肝功能检查、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）实现了病毒学应答，其中36例HDV RNA水平检测不到。在应答者中，ALT水平从67.0 U/mL[四分位间距44.0 - 116.3]显著降至31.5 U/mL[四分位间距24.0 - 36.5，P = 0.001]，AST水平从66.0 U/mL[四分位间距46.5 - 91.0]降至32.5 U/mL[四分位间距28.0 - 38.0，P = 0.021]。HDV RNA中位数从29,800 IU/mL[四分位间距3100 - 375,000]降至0 IU/mL[四分位间距0 - 291，P < 0.001]。未出现显著的应答预测因素。报告了轻度不良事件，包括瘙痒（5.6%）、注射部位反应（1.9%）和流感样综合征（0.9%），无一例停药。
结论
布列韦肽有效降低HDV RNA水平并改善肝功能，安全性良好，为慢性丁型肝炎提供了一种有前景的治疗选择。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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