Liver and Bile
J Hepatol. 2022;77(6):1525–31
Bulevirtide monotherapy for 48 weeks in patients with HDV-related compensated cirrhosis and clinically significant portal hypertension
Background and aims: Bulevirtide (BLV) has recently been conditionally approved for the treatment of chronic hepatitis delta (CHD) in Europe, but its effectiveness and safety in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH) are unknown.
Methods: Consecutive patients with hepatitis delta virus (HDV)-related compensated cirrhosis and CSPH who started BLV 2 mg/day were enrolled in this single-center study. Clinical/virological characteristics were collected at baseline, weeks 4, 8 and every 8 weeks thereafter. HDV RNA was quantified by Robogene 2.0 (lower limit of detection 6 IU/ml).
Results: 18 Caucasian patients with compensated cirrhosis and CSPH under nucleos(t)ide analogue treatment were enrolled: median age was 48 (interquartile range [IQR], 29–77) years, and 67% were male. Median platelet count was 70 (IQR, 37–227) x 103/μl, liver stiffness measurement (LSM) 16.4 (IQR, 7.8–57.8) kPa, alanine aminotransferase (ALT) 106 (IQR, 32–222) U/l, HBsAg 3.7 (IQR, 2.5–4.3) log IU/ml, HDV RNA 4.9 (IQR, 3.3–6.6) log IU/ml. During 48 weeks of BLV monotherapy, HDV RNA declined by 3.1 (IQR, 0.2–4.3) log IU/ml (p < 0.001 vs. baseline), becoming undetectable in 5 patients (23%). A virological response was observed in 14 patients (78%) while a non-response was observed in 2 (11%). ALT decreased to 35 (IQR, 15–86) U/l (p < 0.001 vs. baseline), normalizing in 83% of patients. A combined response was observed in 67% of patients. Aspartate aminotransferase and gamma-glutamyl transferase levels significantly improved. Concerning liver function parameters, albumin values significantly increased and bilirubin remained stable. LSM significantly improved in patients with virological response, while platelet count was unchanged. None of the patients developed decompensating events or hepatocellular carcinoma. BLV was well tolerated, no patient discontinued treatment and the increase in bile acids was fully asymptomatic.
Conclusions: A 48-week course of bulevirtide 2 mg/day monotherapy is safe and effective even for difficult-to-treat patients with hepatitis delta virus-related compensated cirrhosis and clinical and significant portal hypertension.