Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis.

Background And Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for treatment of compensated chronic hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.

Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a European retrospective multicenter real-life study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (HCC, decompensation, liver transplant) were assessed.

Results: 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years, 61% men, ALT 80 (55-130) U/L, liver stiffness measurement (LSM) 18.3 (13.0-26.3) kPa, platelets 94 (67-145) x 10/mm, 54% with esophageal varices, 95% Child Pugh score A, 10% HIV-coinfected, 92% on NUC, median HDV RNA 5.4 (4.1-6.5) Log IU/mL, HBsAg 3.8 (3.4-4.1) Log IU/mL. At weeks (W)48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, only 10% patients reported mild and transient pruritus, independently of bile acid levels. The W96 cumulative risk of de-novo HCC and decompensation was 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n=11 for HCC, n=2 for decompensation).

Conclusion: BLV 2 mg/day monotherapy up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time. Liver-related complications were few.