1Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Hannover, Germany.
2Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany.
3Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
4Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany.
5Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany.
6Department of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany.
7Internal Medicine Department, Goethe University Hospital, Frankfurt, Germany.
8Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
9Department of Internal Medicine I, University of Ulm, Ulm, Germany.
10Department of Medicine II, University Medical Centre Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
11Department of Medicine I, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany.
12I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
13German Center for Infection Research (DZIF), Partner Site Hamburg - Lübeck - Borstel - Riems, Hamburg, Germany.
14Mildred Scheel Cancer Career Center HaTriCS, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
15University Hospital Würzburg, Division of Hepatology, Dept. of Medicine II, Würzburg, Germany.
16Department of Medicine B, University Hospital Münster, Münster, Germany.
17MVZ for Gastroenterology at Bayerischer Platz, Berlin, Germany.
18Ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany.
19D-SOLVE consortium, a EU Horizon Europe funded project (No 101057917).
20Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
21Excellence Cluster Resist, Hannover Medical School, Germany.
22German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany.
Background & aims: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma. Herein, we report the first data from a large multicenter real-world cohort of patients with hepatitis D treated with bulevirtide at a daily dose of 2 mg without additional interferon.
Methods: In a joint effort with 16 hepatological centers, we collected anonymized retrospective data from patients treated with bulevirtide for chronic hepatitis D.
Results: Our analysis is based on data from 114 patients, including 59 (52%) with cirrhosis, receiving a total of 4,289 weeks of bulevirtide treatment. A virologic response defined as an HDV RNA decline of at least 2 log or undetectable HDV RNA was observed in 87/114 (76%) cases with a mean time to virologic response of 23 weeks. In 11 cases, a virologic breakthrough (>1 log-increase in HDV RNA after virologic response) was observed. After 24 weeks of treatment, 19/33 patients (58%) had a virologic response, while three patients (9%) did not achieve a 1 log HDV RNA decline. No patient lost hepatitis B surface antigen. Alanine aminotransferase levels improved even in patients not achieving a virologic response, including five patients who had decompensated cirrhosis at the start of treatment. Treatment was well tolerated and there were no reports of drug-related serious adverse events.
Conclusions: In conclusion, we confirm the safety and efficacy of bulevirtide monotherapy in a large real-world cohort of patients with hepatitis D treated in Germany. Future studies need to explore the long-term benefits and optimal duration of bulevirtide treatment.
Impact and implications: Clinical trials proved the efficacy of bulevirtide for chronic hepatitis D and led to conditional approval by the European Medical Agency. Now it is of great interest to investigate the effects of bulevirtide treatment in a real-world setting. In this work, we included data from 114 patients with chronic hepatitis D who were treated with bulevirtide at 16 German centers. A virologic response was seen in 87/114 cases. After 24 weeks of treatment, only a small proportion of patients did not respond to treatment. At the same time, signs of liver inflammation improved. This observation was independent from changes in hepatitis D viral load. The treatment was generally well tolerated. In the future, it will be of interest to investigate the long-term effects of this new treatment.