BASELINE PREDICTORS OF VIROLOGICAL AND BIOCHEMICAL RESPONSES IN HDV COMPENSATED CIRRHOTIC PATIENTS TREATED WITH BULEVERTIDE MONOTHERAPY ( HEP4Di STUDY)

Background Bulevirtide (BLV) has received EMA approval for treatment of compensated chronic hepatitis Delta (CHD), however predictors of response are still unknown. Methods Consecutive CHD patients with cirrhosis treated with BLV 2 mg/day monotherapy were enrolled in a retrospective multicenter Italian real-life study (HEP4Di). Features at BLV start and on-treatment were collected. Virological response (HDV RNA undetectable or ≥ 2-log decline vs. baseline), biochemical response (ALT <40 U/L) and combined response (biochemical + virological) were assessed. HDV RNA was quantified locally. Results 97 CHD patients with cirrhosis receiving BLV monotherapy up to 96 weeks were included: at BLV start, median age was 52 (29-77) years, 53% males, 100% CPT score A, 52% with varices, 19% with previous ascites, 11% with active HCC, 97% on NUC. Median ALT were 80 (26-1,074) U/L, liver stiffness measurement (LSM) 17.4 (6.4-68.1) kPa, platelets 83 (17-330) x103/mm3, HBsAg 3.7 (0.8-4.5) Log IU/mL and HDV RNA 5.1 (1.2-7.6) Log IU/mL. At BLV treatment weeks (W) W24, W48, W72 and W96, rates of virological response were 53%, 70%, 75% and 80%, respectively, and HDV RNA was undetectable in 16%, 15%, 38% and 33% patients. Biochemical response and combined response were achieved by 65%, 74%, 81% 67% and 38%, 59%, 63%, 67%, respectively. By univariate logistic regression analysis, baseline viremia was the only predictor of virological response: indeed, HDV RNA levels <5 LogIU/mL predicted HDV RNA <1000 IU/mL (OR 3.33, 95% CI 1.19-9.26, p=0.02) and <100 IU/mL (OR 7.30, 95% CI 2.49-21.41, p=0.0003) at week 24, while HDV RNA levels <5 LogIU/mL were associated with HDV RNA undetectability at week 48 (OR 2.77, 95% CI 1.05-7.29, p=0.04). Conversely, none of the baseline features predicted biochemical or combined response. Conclusions In CHD patients with compensated cirrhosis receiving BLV monotherapy, baseline viremia is the only factor associated with virological response.