Effectiveness and safety of three years of bulevirtide monotherapy in patients with HDV-related compensated cirrhosis: the Italian compassionate use program

Background: Bulevirtide (BLV) monotherapy for up to 144 weeks was safe and effective in patients with chronic hepatitis D (CHD) in a phase III trial, but long-term real-world data are limited. We evaluated its effectiveness and safety in patients with HDV-related cirrhosis in clinical practice. Methods: Consecutive patients with HDV-related cirrhosis treated with BLV 2 mg/day monotherapy through the Italian compassionate use program were included. Virological (VR), biochemical (BR), and combined responses (CR), undetectable HDV RNA, virological and biochemical breakthroughs (VBK and BBK), non-invasive tests (NITs), safety, and liver-related events were assessed. Results: Ninety-seven patients were enrolled: median age, 52 years (interquartile range, 40–61); 53% were male; 96% were European; and 92% had Child-Pugh class A cirrhosis. VR, BR, CR, and HDV RNA target-not-detected/below-the-limit-of-detection rates increased over time, with 144-week cumulative incidences of 77%, 84%, 64%, and 53%, respectively. Overall, 11% and 5% of patients experienced a VBK and BBK, respectively. LSM, APRI, FIB-4, and LSPS, but not SSM, declined significantly during therapy. The 3-year cumulative probabilities of decompensation and HCC were 1.3% (95% CI, 1–3%) and 10% (95% CI, 4–19%), respectively. Treatment was well tolerated. Conclusion: Long-term BLV 2 mg/day monotherapy was safe and effective in patients with cirrhosis. Response rates increased over time, while decompensating events remained uncommon.