Overview
Hepatitis D virus (HDV) infection, also known as hepatitis delta, is a significant cause of severe viral hepatitis, requiring coinfection with hepatitis B virus (HBV) for replication 23. HDV superinfection in individuals with chronic HBV infection leads to the most severe form of viral hepatitis 23.Diagnosis
Diagnosis of HDV infection is typically made by detecting HDV RNA or anti-HDV IgM antibodies 13.
Hepatitis B surface antigen (HBsAg) is required for HDV entry into hepatocytes 23.Management
Bulevirtide (BLV), an entry inhibitor, is approved in Europe for chronic HDV infection and has shown efficacy in reducing HDV RNA and intrahepatic HDV infection 3.
* Dosing in trials included 2 mg, 5 mg, or 10 mg daily for 24 or 48 weeks 3.
Tobevebart (a monoclonal antibody) and elebsiran (a small interfering RNA) target HBsAg and are being investigated for HDV treatment 1.
* In a phase 2 trial, tobevibart plus elebsiran every 4 weeks or tobevibart monotherapy every 2 weeks were evaluated 1.
* At week 48, undetectable HDV RNA was observed in 66% of participants receiving tobevibart plus elebsiran and 48% receiving tobevibart monotherapy 1.
* Normalization of ALT levels was observed in 56% and 61% of participants, respectively 1.
* HBsAg levels below 10 IU/mL were achieved in 91% of participants on tobevibart plus elebsiran and 21% on tobevibart monotherapy 1.
Tenofovir disoproxil fumarate monotherapy has been used as a comparator in trials 3.Key Recommendations
Blocking viral entry with agents like bulevirtide diminishes liver inflammation and reduces intrahepatic HDV infection, potentially leading to HDV cure with long-term treatment 3. (Evidence: Moderate)
Tobevebart in combination with elebsiran or as monotherapy shows promise in reducing HDV RNA and normalizing ALT levels in patients with chronic HDV infection 1. (Evidence: Moderate)
Chronic HDV infection is associated with a high incidence of liver-related events, including hepatic decompensation and hepatocellular carcinoma 2. (Evidence: Moderate)References
1 Asselah T, Chattergoon MA, Jucov A, Streinu-Cercel A, Lampertico P, Wedemeyer H et al.. A Phase 2 Trial of Tobevibart plus Elebsiran in Hepatitis D. The New England journal of medicine 2026. link
2 Telep LE, Roulot DM, Singer AW, Stead AE, Da BL, Chee GM et al.. Systematic Review: Incidence of Liver-Related Events in People Living With Hepatitis Delta Virus. Alimentary pharmacology & therapeutics 2025. link
3 Allweiss L, Volmari A, Suri V, Wallin JJ, Flaherty JF, Manuilov D et al.. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies. Journal of hepatology 2024. link