Response-guided long-term treatment of chronic hepatitis D patients with bulevirtide-results of a "real world" study

Aliment Pharmacol Ther. 2022 Jul;56(1):144-154. doi: 10.1111/apt.16945. Epub 2022 May 5.


Background and aim: Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real-life data on BLV efficacy are limited.

Methods: Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV-RNA after 24 weeks were offered PEG-IFN as an add-on therapy in a response-guided manner.

Results: Twenty-three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV-RNA: 2.1 × 105 copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty-two completed ≥24 weeks of treatment (24-137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV-RNA undetectability, but both became HDV-RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG-IFN in eight patients induced an HDV-RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV-RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy.

Conclusion: Long-term BLV monotherapy is safe and effectively decreases HDV-RNA and ALT-even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG-IFN remains to be established. An algorithm for a response-guided BLV treatment approach is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents
  • Hepatitis D, Chronic* / drug therapy
  • Hepatitis Delta Virus / genetics
  • Humans
  • Interferon-alpha / therapeutic use
  • Lipopeptides
  • Liver Cirrhosis / drug therapy
  • Middle Aged
  • RNA, Viral / genetics
  • Treatment Outcome


  • Antiviral Agents
  • Interferon-alpha
  • Lipopeptides
  • RNA, Viral
  • bulevirtide