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Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D
Tarik Asselah1, Vladimir Chulanov1, Pietro Lampertico1
1From Université de Paris-Cité, Department of Hepatology, Hôpital Beaujon Assistance Publique-Hôpitaux de Paris (AP-HP), Centre de Recherche sur l'Inflammation, INSERM Unité Mixte de Recherche 1149, Clichy (T.A.), Hôpital Saint Joseph, Marseille (M.B.), Sorbonne Université, Hôpital Pitié-Salpêtrière, AP-HP, Pitié-Salpétrière, INSERM Unité Mixte de Recherche S 1138, Centre de Recherche des Cordeliers (V.R.), and Hôpital Cochin, AP-HP, Université Paris-Cité (S.P.), Paris, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble (M.-N.H.), and Hospices Civils de Lyon, Université Claude Bernard Lyon 1, INSERM Unité 1052, Lyon Hepatology Institute, Lyon (F.Z.) - all in France; the Infectious Diseases Department, Sechenov University (V.C.), M.F. Vladimirsky Moscow Regional Research and Clinical Institute (P.B.), the Clinic of Modern Medicine (T.S.), and the Research Institute of Emergency Medicine n.a. N.V. Sklifosovsky (V.S.), Moscow, Medical Company "Hepatolog," Samara (V.M.), and South Ural State Medical University, Chelyabinsk (O.S.) - all in Russia; the Department of Pathophysiology and Transplantation, Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, and CRC "A. M. and A. Migliavacca" Center for Liver Disease, University of Milan - both in Milan (P.L.); Klinik für Gastroenterologie, Hepatologie, und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany (H.W.); Matei Bals National Institute of Infectious Diseases (A.S.-C.), Carol Davila University of Medicine and Pharmacy (A.S.-C., G.S.G.), and Dr. Victor Babes Foundation (G.S.G.), Infectious and Tropical Diseases Hospital (S.L.) - all in Bucharest, Romania; Infectious Clinical Hospital "T. Ciorba" (V.P.) and State University of Medicine and Pharmacy "Nicolae Testemitanu" (G.P.), Chisinau, Moldova; and Gilead Sciences, Foster City, CA (D.M., R.-C.M., L.Y., B.L.D., G.C., A.H.L., A.O.).
Bulevirtide combined with peginterferon alfa-2a achieved higher undetectable hepatitis D virus (HDV) RNA rates than bulevirtide alone in a phase 2b trial. This combination therapy offers a promising finite treatment strategy for chronic hepatitis D patients.
Area of Science:
- Hepatology
- Virology
- Clinical Trials
Background:
- Chronic hepatitis D (CHD) treatment guidelines recommend off-label pegylated interferon (peginterferon) alfa-2a.
- Bulevirtide monotherapy demonstrated virologic response in phase 3 trials for CHD.
- The efficacy of finite combination therapy with bulevirtide and peginterferon alfa-2a remains unclear.
Purpose of the Study:
- To evaluate the efficacy of combination therapy with bulevirtide and peginterferon alfa-2a in patients with chronic hepatitis D.
- To compare the outcomes of combination therapy versus bulevirtide monotherapy and peginterferon alfa-2a monotherapy.
- To assess the role of finite treatment duration for combination therapy.
Main Methods:
- A phase 2b, open-label, randomized trial involving 174 patients with chronic hepatitis D.
- Treatment arms included peginterferon alfa-2a alone, bulevirtide (2 mg or 10 mg) plus peginterferon alfa-2a, and bulevirtide (10 mg) alone.
- Primary endpoint: undetectable hepatitis D virus (HDV) RNA at 24 weeks post-treatment; primary comparison: 10 mg bulevirtide + peginterferon alfa-2a vs. 10 mg bulevirtide monotherapy.
Main Results:
- At 24 weeks post-treatment, undetectable HDV RNA was observed in 46% of patients receiving 10 mg bulevirtide + peginterferon alfa-2a, compared to 12% receiving 10 mg bulevirtide alone (P<0.001).
- The combination therapy group showed significantly higher rates of virologic response compared to bulevirtide monotherapy.
- Adverse events, primarily leukopenia, neutropenia, and thrombocytopenia, were mostly grade 1 or 2.
Conclusions:
- Combination therapy with 10 mg bulevirtide and peginterferon alfa-2a is superior to bulevirtide monotherapy for achieving undetectable HDV RNA.
- This combination represents a potentially effective finite treatment strategy for chronic hepatitis D.
- Further research may explore optimized dosing and duration for this combination therapy.
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