Improvement of non-invasive fibrosis tests in HDV cirrhotic patients with clinically significant portal hypertension responding to Bulevirtide monotherapy

Background and aim Non-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. Methods Consecutive 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. Results 46 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). Conclusions In 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.