Improvement of Non-Invasive Fibrosis Tests in HDV Cirrhotic Patients with Clinically Significant Portal Hypertension Responding to Bulevirtide Monotherapy

Background and aimNon-invasive fibrosis tests (NITs) showed significant improvement following antiviral treatment in HBV or HCV-infected patients, whereas data in chronic hepatitis Delta under Bulevirtide (BLV) treatment are lacking.MethodsConsecutive HDV cirrhotic patients with clinically significant portal hypertension (CSPH) according to Baveno VII criteria with a virological response (≥ 2 Log HDV RNA decline vs. baseline) to BLV monotherapy 2 mg/day up to 96 weeks were enrolled in this single-center study. AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) Index and liver stiffness-spleen size-to-platelet ratio score (LSPS) were calculated from clinical variables recorded on-therapy. Liver (LSM) and spleen (SSM) stiffness measurement performed by transient elastography (Fibroscan®) and point shear-wave elastography (ElastPQ) were assessed every 24 weeks.Results46 HDV cirrhotic patients with a virological response to BLV were included: pre-treatment, median age was 52 (30-77) years, 59% males, ALT 98 (30-1,074) U/L, platelets 78 (17-217) x103/mm3, 54% with varices, spleen 15 (9-25) cm, CPT-A 100%, HDV RNA 5.2 (2.4-6.9) Log IU/mL. During BLV monotherapy, serological NIT significantly improved at all timepoints, APRI from baseline 3.5 (0.6-16.5) to 1.2 (0.3-4.5) at week 96 (p<0.001), and FIB-4 from 6.1 (1.3-28.1) to 4.1 (1.2-9.0) (p=0.003). LSM decreased from baseline 17.2 (6.4-68.1) to 13.8 (5.4-54.3) kPa at week 48 (p=0.001) and LSPS from baseline 4.1 (0.5-23.7) to 3.8 (0.3-14.3) at week 48 (p=0.001), whereas no other significant changes were observed throughout weeks 48 and 96. Conversely, other NITs did not significantly modify (baseline vs. week 96): liver ElastPQ 14.3 (4.2-35.2) vs. 10.9 (7.0-22.3) kPa (p=0.54); SSM 50.3 (19.7-100) vs. 47.9 (21.2-97.9) kPa (p=0.69), Spleen ElastPQ 36.9 (12.8-114) vs. 30.6 (17.4-51.8) kPa (p=0.31).ConclusionsIn HDV compensated cirrhotic patients with CSPH and a virological response to BLV monotherapy, long-term treatment led to a significant improvement of serological fibrosis NITs, liver stiffness and LSPS.