HERACLIS_BLV_D: Adherence to Real-Life Therapy With Bulevirtide in Chronic Hepatitis D

Daily subcutaneous bulevirtide (BLV) 2 mg has been approved as first-line treatment for chronic hepatitis D (CHD), but long-term real-world adherence data are limited. We assessed adherence rates during BLV therapy and their impact on treatment response. HERACLIS_BLV_D study (NCT05928000) included adult CHD patients initiating BLV 2 mg/day and followed in routine clinical practice. Virological response (VR) was defined as HDV RNA < 57.5 IU/mL or decline > 2 log₁₀ and biochemical response (BR) as normal ALT (≤ 40 IU/L). Adherence was evaluated through the national prescription system based on executed monthly BLV prescriptions. Treatment discontinuation was defined as no executed BLV prescription for > 3 months at the end of follow-up. Seventy-six patients were included. VR/BR rates were 73%/71% at 12 and 93%/74% at 24 months. Thirteen (17%) patients discontinued BLV (none due to adverse events); 6%-7% per year. Mean adherence among treated patients was 98% ± 6% in 1st year declining to 93% ± 13% in 2nd and 91% ± 17% in 3rd year (p ≤ 0.010). No baseline characteristic was associated with poor (< 90%) or good (≥ 90%) adherence to BLV therapy. Patients with poor vs. good adherence had lower VR rates (1st year: 33% vs. 77%, p = 0.038; 2nd year: 60% vs. 97%, p = 0.030). In conclusion, in clinical practice, < 10% of CHD patients discontinue BLV therapy annually. Adherence is excellent in the first year and remains > 90% until the third year although gradually declines. Poor (< 90%) adherence cannot be predicted but adversely affects the VR rates emphasizing the need for strategies to support long-term treatment retention.