Real-world evidence shows comparable Bulevirtide effectiveness in hepatitis D patients with and without cirrhosis: results from the prospective nationwide D-Shield multicenter study

Background and aims: Bulevirtide (BLV) has been available in Italy since May 2023 for patients with chronic hepatitis Delta (CHD), but no studies have addressed features of patients treated with BLV and their responses to treatment yet. Method: CHD patients starting BLV 2 mg/day as monotherapy were included in a multicenter prospective real-life Italian study (DSHIELD). Patients’ characteristics and treatment responses were assessed at baseline and trimonthly afterwards in patients with or without cirrhosis. The primary endpoint was the achievement of a virological response, defined as a reduction inHDVRNA>2LogIU/mL compared to baseline or HDV RNA undetectable. Results: 404 patients from 38 centers were enrolled in this ongoing study: 303 (75%)cirrhotics and,101 non-cirrhotics (25%). At baseline, median HDV RNAwas 5.1 (1.5–8.2) vs. 5.7 (2.3–7.4) Log IU/ml (p= 0.005), ALT 75 (12–1,074) vs. 75 (19–513) U/L (p=0.20). Median age 55 (24–82) vs. 55 (26–76), 55% vs. 55% men, 97% vs. 93% on NA therapy; 94% vs. 94% European origin. Among cirrhotics, 40% had varices, 10% previous history of HCC, 10% previous history of ascites, 3% of varices hemorrhage, 6% were decompensated. As of the end of November 2024, 340 patients (257 cirrhotics and 83 non-cirrhotics) completed 24 weeks and 203 (160 cirrhotics, 43 non-cirrhotics) patients have completed 48 weeksof treatment.ALT declinedin both groups at week 24 (median ALT levels 35 vs. 35 U/L, p=0.60) and at week 48 (31 vs. 31U/L, p=0.90). HDV RNA decline was more pronounced in non-cirrhotics at week 24 (3.5 vs. 3.8 Log IU/mL, p= 0.04), but not at week 48 (2.9 vs. 3.2 Log IU/mL, p=0.06). Virological, biochemical and combined responses were achieved by 47% vs. 42% (p=0.60),64%vs.69%(p=0.51),and34%vs.32%(p=0.89)ofpatients at week 24; 68%vs. 50% (p=0.04), 69% vs. 68% (p=0.87), and 49% vs. 34% (p=0.06) of patients at week 32, and by 66% vs. 65% (p=1), 73% vs. 55%(p=0.06), and54%vs.33%(p=0.05),ofpatientsatweek48in cirrhotics vs. non-cirrhotics, respectively. At the same time points HDV RNA undetectability (defined as target not detected or 1 Log IU/ mLbut <2 log IU/mL compared to baseline), was achieved by 24% vs. 23% (p=1), and 20% vs.14% (p=0.76) of cirrhotics vs. non cirrhotics patients at week32and48,respectivelyandavirologicalresponseby 44% vs. 26% (p=0.09) and 53% vs. 48% (p=0.81), respectively. Conclusion: D-SHIELD is the largest single country study on BLV treatment for CHD in Europe. Virological, biochemical and combined responses through week 48 were overall similar between patients with and without cirrhosis.