Author information

¹Dept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.

²Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

³Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

⁴Division of Hepatology, Dept. of medicine II, University Hospital Wuerzburg, Wuerzburg, Germany.

⁵Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany.

⁶Department of Internal Medicine I, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.

⁷Department of Medicine B, University Hospital Muenster, Muenster, Germany.

⁸Department of Gastroenterology, Medical Center Osnabrueck, Osnabrueck, Germany.

⁹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.

¹⁰D-SOLVE consortium, a EU Horizon Europe funded project (No 101057917).

¹¹Excellence Cluster Resist, Hannover Medical School, Germany.

¹²German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany.

¹³CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Abstract

Background aims: Chronic hepatitis D is the most debilitating form of viral hepatitis frequently progressing to cirrhosis and subsequent decompensation. However, the HDV entry inhibitor bulevirtide is only approved for antiviral treatment of patients with compensated disease. We aimed for the analysis of real-world data on the off-label use of bulevirtide in the setting of decompensated liver cirrhosis.

Approach results: We conducted a retrospective study in HDV-patients with decompensated liver disease at German, Austrian and Italian centers. We included 19 patients (47% male, mean age: 51 y) with liver cirrhosis Child-Pugh B. Median MELD score was 12 (range 9-17) at treatment initiation. Median observation period was 41 weeks. Virologic response was achieved in 74% and normal ALT was observed in 74%. Combined response was achieved by 42%. The most relevant adverse events included self-limited ALT flares, an asymptomatic increase in bile acids and need for liver transplantation. Despite bile acid increases adverse events were considered unrelated. Clinical and laboratory improvement from Child-Pugh B to A occurred in 47% (n=9/19). Improvements in the amount of ascites were observed in 58% of patients initially presenting with ascites (n=7/12).

Conclusions: This report on off-label bulevirtide treatment in patients with decompensated HDV cirrhosis shows similar virologic and biochemical response rates as observed in compensated liver disease. Significant improvements were observed on surrogates of hepatic function and portal hypertension. However, this improvement was not seen in all patients. Controlled trials are needed to confirm safety and efficacy of bulevirtide in decompensated HDV-cirrhosis.