Improvement of clinical parameters in HDV patients with advanced compensated cirrhosis treated with Bulevirtide monotherapy for 48 weeks

Background and Aim Bulevirtide (BLV) has been conditionally approved for treatment of compensated chronic hepatitis Delta in Europe, however long-term outcomes of HDV patients with compensated cirrhosis treated with BLV monotherapy are currently unknown. Methods Consecutive HDV patients with compensated cirrhosis who received BLV monotherapy for 48 weeks were enrolled in this single-center study. Clinical variables were collected at baseline, weeks 4, 8 and every 8 weeks thereafter. Results 20 Caucasian patients under nucleos(t)ide analogue (NUC) treatment were included: median age 49 years, 65% males, liver stiffness measurement (LSM) 16.8 kPa, 80% with varices. At baseline, ALT levels were 110 U/L, AST 92 U/L, GGT 52 U/L, albumin 3.9 g/dL, platelets 72 × 103/mm3, IgG 2285 mg/dL, HDV RNA 4.9 UI/mL. CPT score was A in all patients. Following 48 weeks of BLV monotherapy (2 mg/day in n=18 and 10 mg/day in n=2), HDV RNA declined by 3.1 Log IU/mL and became undetectable in 39%; 89% of patients achieved a virological response (undetectable HDV RNA or ≥2 Log decline vs. baseline). At week 48, most biochemical parameters improved: ALT (normalizing in 85% of patients), AST, GGT, IgG and albumin (p<0.001 for all comparisons). Four out of 5 patients with CPT score A6 improved to A5 at week 48. Bilirubin, platelets and HBsAg remained unchanged, LSM significantly declined in viral responder patients (p=0.03). Among 9 patients with baseline small varices not needing prophylaxis, varices disappeared in 2 cases. De-novo decompensation due to portal vein thrombosis occurred in one patient, de-novo HCC in two, three underwent liver transplantation and one patient died due to BLV-unrelated causes. BLV was well tolerated, an asymptomatic increase in bile acids occurred. Conclusions Liver function parameters improved in HDV patients with compensated cirrhosis treated with BLV monotherapy for 48 weeks. Esophageal varices disappeared in some patients. Bulevirtide (BLV) has been conditionally approved for treatment of compensated chronic hepatitis Delta in Europe, however long-term outcomes of HDV patients with compensated cirrhosis treated with BLV monotherapy are currently unknown. Consecutive HDV patients with compensated cirrhosis who received BLV monotherapy for 48 weeks were enrolled in this single-center study. Clinical variables were collected at baseline, weeks 4, 8 and every 8 weeks thereafter. 20 Caucasian patients under nucleos(t)ide analogue (NUC) treatment were included: median age 49 years, 65% males, liver stiffness measurement (LSM) 16.8 kPa, 80% with varices. At baseline, ALT levels were 110 U/L, AST 92 U/L, GGT 52 U/L, albumin 3.9 g/dL, platelets 72 × 103/mm3, IgG 2285 mg/dL, HDV RNA 4.9 UI/mL. CPT score was A in all patients. Following 48 weeks of BLV monotherapy (2 mg/day in n=18 and 10 mg/day in n=2), HDV RNA declined by 3.1 Log IU/mL and became undetectable in 39%; 89% of patients achieved a virological response (undetectable HDV RNA or ≥2 Log decline vs. baseline). At week 48, most biochemical parameters improved: ALT (normalizing in 85% of patients), AST, GGT, IgG and albumin (p<0.001 for all comparisons). Four out of 5 patients with CPT score A6 improved to A5 at week 48. Bilirubin, platelets and HBsAg remained unchanged, LSM significantly declined in viral responder patients (p=0.03). Among 9 patients with baseline small varices not needing prophylaxis, varices disappeared in 2 cases. De-novo decompensation due to portal vein thrombosis occurred in one patient, de-novo HCC in two, three underwent liver transplantation and one patient died due to BLV-unrelated causes. BLV was well tolerated, an asymptomatic increase in bile acids occurred. Liver function parameters improved in HDV patients with compensated cirrhosis treated with BLV monotherapy for 48 weeks. Esophageal varices disappeared in some patients.