Effectiveness, Safety and Patient-Reported Outcomes of Bulevirtide Therapy in Chronic Hepatitis Delta: Real-World Evidence From a Prospective Observational Study.

Chronic hepatitis delta (CHD) is the most severe form of viral hepatitis and is associated with accelerated progression to cirrhosis and liver failure. Bulevirtide has shown promising results in trials, but real-world data on its effectiveness, safety and impact on patient-reported outcomes (PROs) remain limited. To evaluate the effectiveness, safety, and PROs (quality-of life-QoL; adherence) of bulevirtide therapy in CHD patients undergoing a dedicated pharmacist-led patient-education program (PEP). A prospective observational study enrolled 31 consecutive CHD patients receiving bulevirtide 2 mg daily at a tertiary referral centre. Virological, biochemical and combined responses were assessed at weeks 24, 48 and 60. QoL (through EQ-5D-5L questionnaire), adherence (proportion of days covered), and adverse events were monitored during follow-up. Bulevirtide significantly reduced HDV-RNA by week 24 (p < 0.01), with further reductions at week 48 (p = 0.05) and 60 (p < 0.01). Liver tests improved significantly from baseline to week 24 (p < 0.01) and remained stable. Combined response was achieved in 43.7% of patients by week 60. QoL improved significantly (p = 0.03), and adherence was excellent (≥ 90%). Adverse events were mostly mild and transient. In real-world clinical practice, bulevirtide achieved sustained virological and biochemical improvements with favourable safety and quality-of-life outcomes, confirming its effectiveness in routine management of CHD. While the 60-week data (n = 16) are exploratory due to the sample size, these findings confirm its effectiveness and safety in routine management of CHD.