Long-term Bulevirtide monotherapy in patients with HDV-related compensated cirrhosis: effectiveness, safety and clinical outcomes from the retrospective multicenter european study (Save-D)

Abstract

Background

Bulevirtide (BLV) has been approved by EMA for treatment of compensated chronic hepatitis D virus (HDV) infection, however, long-term real-life effectiveness and safety data in large cohorts of HDV patients with cirrhosis treated beyond week 48 are lacking.

Methods

Consecutive HDV patients with cirrhosis starting BLV 2 mg/day sc since September 2019 were included in a retrospective multicenter real-life European study (SAVE-D). Virological (HDV-RNA undetectable or ≥2-log decline vs. baseline), biochemical (ALT <40 U/L), combined response (biochemical + virological), adverse events and liver-related outcomes were assessed.

Results

244 patients treated with BLV monotherapy up to 120 weeks [median follow-up: 92 (range 24-120) weeks] were included: age 49 years, 61% men, ALT 80 U/L, LSM 18.3 kPa, platelets 94 × 10³/mm³, 95% CPT score A, 54% with varices, 10% HIV-positive, 15% with a history of ascites, 6% with active HCC, 92% on NUC. Baseline HDV-RNA and HBsAg levels were 5.4 (4.1-6.5) log IU/mL and 3.8 (3.4-4.1) log IU/mL. Virological, biochemical and combined responses at W48, W96, W120 were 64%, 71%, and 74%, 58%, 63%, 59% and 43%, 51%, 49%, respectively. HDV RNA undetectability was achieved by 27%, 40%, and 41%. Baseline HDV-RNA <5 LogIU/mL was the only predictor of HDV-RNA undetectability at week 48. AST, GGT, albumin, IgG and LSM values significantly improved during treatment. Bile acids significantly increased but only 11% of patients reported mild and transient pruritus. The W120 cumulative incidences of de-novo HCC and decompensation were 6.1% (95% CI 3-9%) and 3.3% (95% CI 1-6%), respectively. 18 patients underwent liver transplantation (HCC n=15; decompensation n=3), 8 patients died due to BLV-unrelated causes.

Conclusions

BLV 2 mg/day monotherapy up to 120 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses continued to increase and only few patients experienced liver-related complications.