Virological and Clinical Outcomes of Patients with HDV-related Compensated Cirrhosis Treated with Bulevirtide Monotherapy: the Retrospective Multicenter European Study (Save-D)

BackgroundBulevirtide (BLV) received EMA approval for treatment of chronic compensated hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.MethodsConsecutive HDV patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a retrospective multicenter real-life European study (SAVE-D). Patients’ characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (HCC, decompensation, liver transplant) were assessed.Results215 patients with HDV compensated (CPT-A) cirrhosis receiving BLV monotherapy for a median of 72 (24-120) weeks were included: at BLV start, age was 49 (18-81) years, 60% men, ALT 78 (23-1,074) U/L, liver stiffness measurement (LSM) 18.3 (6.4-75.0) kPa, platelets 91 (17-454) x 103/mm3, 54% with varices, 8% HIV-positive, 6% with previous ascites, 6% with active HCC, 91% on NUC, median HDV RNA 5.5 (1.5-8.5) log IU/mL and HBsAg 3.7 (0.8-4.7) log IU/mL. Virological responses and HDV-RNA undetectability at W24, W48, W72, W96 were 54%, 68%, 68%, 77% and 18%, 32%, 41% and 46%, respectively. Biochemical and combined responses were 54%, 63%, 60%, 57%, and 34%, 48%, 48%, and 50%, respectively. Patients with <1 log HDV-RNA decline vs. baseline declined from 21% at W24 to 8% at W96. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Bile acids significantly increased, 9% patients reported mild and transient pruritus, 3% injection site reactions. The W96 cumulative risks of de-novo HCC (n=7) and decompensation (n=6) were 3.8% (95% CI 2-7%) and 3.2% (95% CI 1-6%), respectively. 7 patients underwent liver transplantation and 4 died of BLV-unrelated causes.ConclusionsBLV 2 mg/day monotherapy up to 96 weeks was safe and effective in patients with HDV-related compensated cirrhosis. Virological and clinical responses increased over time and liver-related events were few.