Caroline Zöllner, Anne Minello, Marie-Noelle Hilleret, Thomas Reiberger, Mathias Jachs, Heiner Wedemeyer, Hartmut Schmidt, Uta Merle, George Papatheodoridis, Frank Tacke, Christopher Dietz-Fricke, Maria Paola Anolli, Gianpiero D'Offizi, Francesco di Maria, Victor De Ledinghen, Ivana Carey, Florian Van Bömmel, Mariana Cardoso, Adriano Pellicelli, Bruno Roche, Jérome Dumortier, Frederic Heluwaert, Isabelle Ollivier, Alessandro Loglio, Francesca Pileri, Monia Maracci, Jean-Pierre Arpurt, Karl Barange, Teresa A Santantonio, Margarita Papatheodoridi, Sophie Metivier, Nathalie Ganne, Louis D'Alteroche, Isabelle Rosa, Dominique Roulot, Anne Gervais, Mauro Viganò, Alessandra Mangia, Maurizia R Brunetto, Nasser Semmo, Alessia Ciancio, Stanislas Pol, Matteo Tonnini, Gabriella Verucchi, Eric Billaud, Kosh Agarwal, Xavier Causse, Nicola Coppola, Massimo Puoti, Elisabetta Degasperi, Soo Aleman, Christoph Schramm, Pietro Lampertico, Alessandro Federico, Fabien Zoulim
Journal: Journal of hepatology 2025;82(6):1012-1022
PMID: 39793613
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
IMPACT AND IMPLICATIONS
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.
Copyright © 2025 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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