S1746 Efficacy of Bulevirtide in the Treatment of Chronic Hepatitis D Infection: A Systematic Review

Le résumé fourni par la source

Introduction: Hepatitis D virus (HDV) is a satellite ribonucleic acid (RNA) virus that requires hepatitis B virus (HBV) surface antigen for entry into hepatocytes and for propagation. HDV is estimated to affect around 15 million people worldwide. Long-term coinfection with HBV and HDV is considered to be the most serious type of chronic viral hepatitis. Currently, there is an absence of approved HDV therapies. However, bulevirtide is a novel therapeutic agent being studied for treating Hepatitis D. Its mechanism of action is notably specific; it targets and binds to the sodium taurocholate co-transporting polypeptides (NTCP) on hepatocytes. NTCP is a receptor that facilitates the entry of HDV into liver cells. By blocking this entry point, Bulevirtide effectively prevents the virus from infecting new cells and proliferating within the host, blocking the lifecycle of the virus. Methods: A literature search across PubMed, Embase, and Cochrane identified 2 clinical trials (N=268), 2 retrospective cohort studies (N=133), and 3 prospective studies (N=48). Extracted efficacy outcomes included the number of people who achieved undetectable or ≥2 log10 IU/ml decrease in HDV RNA level, and the number of people who had normalization of the Alanine transaminase (ALT) level. Results: The efficacy of bulevirtide in treating Hepatitis D was evaluated across the multiple studies included in this systematic review (Table 1) with a total of 419 patients from 7 studies. One study compared bulevirtide to a placebo. One study compared bulevirtide and tenofovir disoproxil fumarate (TDF) to TDF alone. Three studies tested the efficacy of bulevirtide only, and 1 study bulevirtide and TDF without a comparison group. Undetectable or ≥2 log10 IU/ml decrease in HDV RNA level was achieved in a total of 70% (257/370) of people receiving bulevirtide. Furthermore, normalization of ALT was achieved in 54% (153/280) of people who received bulevirtide. Two studies compared bulevirtide to placebo/TDF. Undetectable or ≥2 log10 IU/ml decrease in HDV RNA level was achieved in a total of 67% (127/189) compared to only 4% (3/79) who received a placebo/TDF. Normalization of ALT was achieved in 50% (93/189) of people who received bulevirtide in compared to 10% (8/79) in patients who received placebo/TDF. Conclusion: Bulevirtide demonstrated substantial efficacy in reducing HDV RNA levels and normalizing ALT levels in patients with Hepatitis D. These findings support bulevirtide as a promising treatment option for this challenging infection. Table 1. - Studies looking at the efficacy of bulevirtide included in our systematic review Author Name of the study Type of the study Total Number of patients Duration Treatments Studied Number of patients who received Bulevirtide Number of patients who received placebo/comparison drug Number of patients who had Undetectable or ≥2 log10 IU/ml decrease in HDV RNA who received Bulevirtide Number of patients who had Undetectable or ≥2 log10 IU/ml decrease in HDV RNA who received placebo/comparison drug Number of patients who had normalized ALT levels who received Bulevirtide Number of patients who had normalized ALT levels who received placebo/comparison drug Wedemeyer H. et. Al 2023 A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D Phase 3 randomized controlled trial 150 48 weeks Bulevirtide vs Placebo 99 51 73 2 53 6 Wedemeyer H. et. Al 2023 Safety and efficacy of Bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomized, parallel-group, open-label, phase 2 trial Phase 2 randomized controlled trial 118 24 weeks Bulevirtide and tenofovir disoproxil fumarate (TDF) vs TDF alone 90 28 54 1 40 2 Degasperi E. et al 2022 Bulevirtide monotherapy for 48 weeks in patients with HDV-related compensated cirrhosis and clinically significant portal hypertension Prospective study 18 48 weeks Bulevirtide 18 N/A 14 N/A 15 N/A Dietz-Fricke C. et al 2023 Safety and efficacy of off-label Bulevirtide monotherapy in patients with HDV with decompensated Child-B cirrhosis A real-world case series Retrospective study 19 N/A Bulevirtide 19 N/A 14 N/A 14 N/A Dietz-Fricke C. et al 2023 Treating hepatitis D with Bulevirtide – Real-world experience from 114 patients Retrospective study 114 N/A Bulevirtide 114 N/A 87 N/A 14 N/A Herta T. et al 2022 Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection Prospective study 7 24 weeks Bulevirtide plus Tenofovir Disoproxil Fumarate 7 N/A 5 N/A 3 N/A Jachs M. et al 2022 Response-guided long-term treatment of chronic hepatitis D patients with Bulevirtide—results of a “real world” study Prospective study 23 24 weeks Bulevirtide 23 N/A 10 N/A 14 N/A

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.