Author information

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

²Rare Liver Disease (RALID) Center of the European Reference Network for Rare Hepatological Diseases (ERN RARE-LIVER), Medical University Vienna, Vienna, Austria.

³Department of Medicine I and Christian Doppler Laboratory on Iron and Phosphate Biology, Medical University of Innsbruck, Innsbruck, Austria.

⁴Center for Virology, Medical University of Vienna, Vienna, Austria.

Abstract

Background & aims: Bulevirtide (BLV) is a novel antiviral drug licensed for the treatment of chronic hepatitis D. Data on the safety and efficacy of stopping BLV therapy upon long-term HDV-RNA suppression are scarce.

Methods: A total of seven patients (age, 31-68 years, four with cirrhosis) included in a prospective Austrian HDV registry discontinued BLV treatment (duration, 46-141 weeks) upon long-term HDV suppression (HDV-RNA negativity, 12-69 weeks). Pegylated interferon-?2a was used in combination with BLV in two patients. HDV-RNA, alanine aminotransferase, and quantitative HBsAg levels were closely monitored during treatment-free follow-up.

Results: The seven patients were followed up for 14 to 112 weeks. Six patients completed ≥24 weeks of follow-up. HDV-RNA became detectable again in three patients within 24 weeks, whereas one additional patient showed an HDV-RNA relapse after almost 1 year. All patients who relapsed at any point had undergone BLV monotherapy. Meanwhile, HDV-RNA remained undetectable in two patients who were treated with BLV + pegylated interferon-?2a. Only one patient showed significant alanine aminotransferase increases within 24 weeks of follow-up. BLV was reintroduced in three patients after 13-62 BLV-free weeks and was well tolerated, and all patients achieved virologic response again.

Conclusions: BLV discontinuation upon long-term HDV-RNA suppression seems safe. Retreatment with BLV was effective in case of virologic relapse. These findings are within a limited number of patients, and future studies are needed to define stopping rules and further investigate the safety of stopping BLV.

Impact and implications: Limited data exist on stopping bulevirtide (BLV) treatment in patients who achieve long-term HDV-RNA suppression. In a small cohort of seven Austrian patients discontinuing BLV therapy, HDV-RNA relapses were observed in four patients during long-term follow-up, whereas significant alanine aminotransferase increases were recorded in only one. Retreatment with BLV was effective in relapsers. The safety and efficacy of stopping BLV needs to be further studied in larger cohorts.