Degasperi Elisabetta, Anolli Maria Paola, Jachs Mathias, Reiberger Thomas, De Ledinghen Victor, Metivier Sophie, D'Offizi Gianpiero, di Maria Francesco, Schramm Christoph, Schmidt Hartmut, Zöllner Caroline, Tacke Frank, Dietz-Fricke Christopher, Wedemeyer Heiner, Papatheodoridi Margarita, Papatheodoridis George, Carey Ivana, Agarwal Kosh, Van Bömmel Florian, Brunetto Maurizia R, Cardoso Mariana, Verucchi Gabriella, Ciancio Alessia, Zoulim Fabien, Aleman Soo, Semmo Nasser, Mangia Alessandra, Hilleret Marie-Noelle, Merle Uta, Santantonio Teresa A, Coppola Nicola, Pellicelli Adriano, Roche Bruno, Causse Xavier, D'Alteroche Louis, Dumortier Jérome, Ganne Nathalie, Heluwaert Frederic, Ollivier Isabelle, Roulot Dominique, Viganò Mauro, Loglio Alessandro, Federico Alessandro, Pileri Francesca, Maracci Monia, Tonnini Matteo, Arpurt Jean-Pierre, Barange Karl, Billaud Eric, Pol Stanislas, Gervais Anne, Minello Anne, Rosa Isabelle, Puoti Massimo, Lampertico Pietro
Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
J Hepatol. 2025 Jun;82(6):1012-1022. doi: 10.1016/j.jhep.2024.12.044. Epub 2025 Jan 8.
BACKGROUND & AIMS: Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking.
Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (hepatocellular carcinoma [HCC], decompensation, liver transplant) were assessed.
A total of 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years and 61% were men; median ALT, LSM and platelet count were 80 (55-130) U/L, 18.3 (13.0-26.3) kPa, and 94 (67-145) x10/mm, respectively; 54% had esophageal varices, 95% Child-Pugh A cirrhosis, and 10% HIV coinfection; 92% were on nucleos(t)ide analogues; median HDV RNA and HBsAg were 5.4 (4.1-6.5) log IU/ml and 3.8 (3.4-4.1) log IU/ml, respectively. At weeks 48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, but only 10% reported mild and transient pruritus, which was independent of bile acid levels. The week 96 cumulative risks of de novo HCC and decompensation were 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n = 11 for HCC, n = 2 for decompensation).
BLV 2 mg/day monotherapy for up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time, while the incidence of liver-related complications was low.
Bulevirtide 2 mg/day is EMA approved for the treatment of compensated chronic hepatitis delta; however, real-world data in large cohorts of patients with cirrhosis are lacking. Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real-world cohort of patients with HDV-related cirrhosis, including patients with clinically significant portal hypertension. Liver function tests and liver stiffness improved, suggesting a potential clinical benefit in patients with advanced liver disease, while the incidence of de novo liver-related events (hepatocellular carcinoma and decompensation) was low during the 96-week study period.
布立伏定（BLV）2毫克/天已获欧洲药品管理局（EMA）批准用于治疗代偿性慢性丁型肝炎病毒（HDV）感染；然而，缺乏大量肝硬化患者的真实世界数据。
2019年9月起开始使用2毫克/天布立伏定的连续性HDV感染肝硬化患者被纳入一项欧洲回顾性多中心真实世界研究（SAVE-D）。收集布立伏定治疗前及治疗期间的患者特征。评估病毒学、生化指标、联合反应、不良事件及肝脏相关事件（肝细胞癌[HCC]、失代偿、肝移植）。
共纳入244例接受布立伏定单药治疗的HDV相关肝硬化患者，中位治疗时间为92（四分位间距71 - 96）周：开始使用布立伏定时，中位（四分位间距）年龄为49（40 - 58）岁，61%为男性；中位丙氨酸氨基转移酶（ALT）、肝脏硬度值（LSM）及血小板计数分别为80（55 - 130）U/L、18.3（13.0 - 26.3）kPa及94（67 - 145）×10⁹/mm³；54%有食管静脉曲张，95%为Child-Pugh A级肝硬化，10%合并人类免疫缺陷病毒（HIV）感染；92%正在使用核苷（酸）类似物；中位HDV RNA及乙型肝炎表面抗原（HBsAg）分别为5.4（4.1 - 6.5）log IU/ml及3.8（3.4 - 4.1）log IU/ml。在第48周和第96周时，分别有65%和79%、61%和64%、44%和54%的患者出现病毒学、生化指标及联合反应。在整个治疗过程中，天门冬氨酸氨基转移酶（AST）、γ-谷氨酰转移酶（GGT）、白蛋白、免疫球蛋白G（IgG）及LSM值均显著改善。大多数患者血清胆汁酸水平升高，但只有10%报告有轻度短暂瘙痒，且与胆汁酸水平无关。第96周时，新发HCC和失代偿的累积风险分别为3.0%（95%置信区间2 - 6%）和2.8%（95%置信区间1 - 5%）。13例（5%）患者接受了肝移植（11例因HCC，2例因失代偿）。
布立伏定2毫克/天单药治疗长达96周对HDV相关肝硬化患者安全有效。病毒学和临床反应随时间增加，而肝脏相关并发症的发生率较低。
布立伏定2毫克/天已获EMA批准用于治疗代偿性慢性丁型肝炎；然而，缺乏大量肝硬化患者的真实世界数据。在一个大型真实世界的HDV相关肝硬化患者队列中，包括有临床显著门静脉高压的患者，布立伏定2毫克/天单药治疗长达96周是安全有效的（第96周：病毒学反应79%、生化指标反应64%、联合反应54%）。肝功能检查和肝脏硬度有所改善，提示对晚期肝病患者有潜在临床益处，而在96周研究期间新发肝脏相关事件（肝细胞癌和失代偿）的发生率较低。
