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Response-guided bulevirtide ± pegylated interferon alfa-2a: Long-term outcomes observed in the nationwide Austrian
Michael Schwarz1, Marlene Hintersteininger2, Caroline Schwarz3
1Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Department of Internal Medicine 2, Gastroenterology and Hepatology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St Pölten, Austria.
Insights
Bulevirtide (BLV) shows high response rates in chronic hepatitis D patients. Add-on pegylated interferon alfa-2a (PEG-IFN) improves viral control, potentially enabling finite treatment duration.
Area of Science:
- Hepatology
- Virology
- Pharmacology
Background:
- Chronic hepatitis D (CHD) can rapidly progress to advanced chronic liver disease (ACLD).
- Bulevirtide (BLV) is an approved treatment for CHD, but optimal use and finite treatment potential require further study.
- Real-world data on BLV efficacy and add-on therapies are crucial for managing CHD.
Purpose of the Study:
- To evaluate the efficacy of bulevirtide (BLV) in a real-world cohort of chronic hepatitis D (CHD) patients.
- To assess the impact of add-on pegylated interferon alfa-2a (PEG-IFN) in patients with suboptimal response to BLV.
- To explore the potential for finite treatment duration based on virological response.
Main Methods:
- A nationwide cohort study included 61 Austrian patients treated with BLV.
- Virological, biochemical, and combined response were assessed every six months up to 24 months.
- Pegylated interferon alfa-2a (PEG-IFN) was administered to patients with suboptimal response to BLV monotherapy.
Main Results:
- Bulevirtide (BLV) treatment led to sustained virological, biochemical, and combined response rates through 24 months.
- Add-on PEG-IFN in suboptimal responders significantly reduced HDV-RNA and HBsAg levels.
- 32.8% of patients achieved undetectable HDV-RNA (TND), and 10 patients discontinued treatment with sustained response.
Conclusions:
- Bulevirtide demonstrates high efficacy in a real-world setting for chronic hepatitis D.
- Add-on PEG-IFN is effective in improving viral control in suboptimal BLV responders.
- Achieving sustained undetectable HDV-RNA may identify candidates for finite bulevirtide treatment.
Background & Aims:
Chronic hepatitis D (CHD) often progresses to advanced chronic liver disease (ACLD). Bulevirtide (BLV) is approved for CHD, yet treatment duration, management of suboptimal response, and the potential for finite treatment remain unclear.
Methods:
Patients receiving BLV at 10 Austrian centers were included. Virological, biochemical, and combined response (VR/BR/CR) were assessed every 6 months (M6-M24). Pegylated interferon alfa-2a (PegIFN) was offered to suboptimal responders.
Results:
Sixty-one patients (median age: 45 years, 60.7% men, ACLD: 68.9%) receiving BLV for a median of 29.0 months were included. VR (Month [M]6: 36.4%, M12: 64.2%, M24: 61.9%), BR (M6: 56.4%, M12: 69.8%, M24: 66.7%), and CR (M6: 25.5%, M12: 47.2%, M24: 42.9%) were maintained for 2 years. Liver stiffness and systemic inflammation (i.e. C-reactive protein [CRP] and procalcitonin [PCT]) decreased under BLV treatment (all p <0.01). Nineteen patients (31.1%) received add-on PegIFN to BLV monotherapy after a median of 10.5 months, inducing a further HDV-RNA decline by 1.65 (IQR 0.81-2.11) log10 copies/ml and reductions in HBsAg levels by 0.08 (IQR 0.02-0.12) log10 IU/L after 24 weeks of combined therapy (both p <0.01). Overall, 32.8% (20/61 patients) achieved HDV-RNA target not detected (TND). Ten (seven BLV mono and three BLV + PegIFN) stopped treatment after 23.0 (IQR 12.0-29.0) months. Seven patients maintained HDV-RNA TND through the last follow-up (median 36.0 months), whereas three patients relapsed but achieved TND again following BLV retreatment.
Conclusions:
High response rates to BLV were observed in this nationwide cohort. In suboptimal BLV responders, PegIFN add-on was associated with a significant and partly sustained decline in HDV-RNA and HBsAg, indicating a relevant contribution to long-term viral infection control. Sustained negative HDV-RNA could help identify candidates for finite BLV treatment.
Impact And Implications:
CHD is a severe form of viral hepatitis with rapid progression to cirrhosis and hepatocellular carcinoma, highlighting the need for effective treatments. In this real-world cohort of 61 Austrian patients, BLV significantly reduced HDV-RNA, alanine aminotransferase, and liver stiffness (p <0.001). Add-on PegIFN resulted in a further decline of HDV-RNA and HBsAg by 24 weeks of combined treatment (p <0.01) in 19 patients with suboptimal response to BLV treatment, and long-term HDV-RNA TND allowed elective treatment discontinuation in 10 patients under close surveillance.
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