Hintersteininger, M., Schwarz, M., Schwabl, P., Hartl, L., Balcar, L., Hofer, B. S., Kramer, G., Sebesta, C., Thöne, P., Attalla, P., Gschwantler, M., Trauner, M., Mandorfer, M., Reiberger, T., & Jachs, M. (2026). Correlation of Bile Acid Dynamics to Bulevirtide Response and Disease Severity in Patients With Hepatitis D
Marlene Hintersteininger, Michael Schwarz, Philipp Schwabl, Lukas Hartl, Lorenz Balcar, Benedikt Silvester Hofer, Georg Kramer, Christian Sebesta, Paul Thöne, Patrik Attalla, Michael Gschwantler, Michael Trauner, Mattias Mandorfer, Thomas Reiberger, Mathias Jachs
Faculty of Medicine Vienna
Medical University of Vienna, University Hospital of Sankt Pölten, Fourth Department of Internal Medicine, Klinik Ottakring
https://doi.org/10.1111/apt.70675
Abstract
BACKGROUND: Bulevirtide (BLV) blocks hepatitis D virus (HDV) entry by targeting the sodium taurocholate co-transporting polypeptide (NTCP). This study assessed the relationship between bile acid (BA) levels and antiviral response to BLV.
METHODS: Serum BA levels were monitored in HDV-infected patients pre-, under, and post BLV treatment. Virologic response (VR) was defined by ≥ 2log10 decline in HDV-RNA and discriminated versus virologic non-response (VNR). Delta BA levels (ΔBA) were calculated and analysed in relation to HDV-RNA dynamics. Finally, the effect of BLV treatment cessation on BA was investigated.
RESULTS: Twenty five patients (48% male; advanced chronic liver disease [ACLD]: 92.0%, 17 patients with VR at W48) were included. Median baseline BA levels were significantly higher in patients with ACLD and portal hypertension (n = 10; 19.2 vs. 5.1 μmol/L; p = 0.015). No difference in median on-treatment BA levels was detected between patients achieving VR or VNR at W24 (VR: 25.4 vs. VNR: 22.7 μmol/L; p = 1.000) and W48 (VR: 25.4 vs. VNR: 20.8 μmol/L; p = 1.000). Additionally, ΔBA from baseline to W48 did not differ between VR and VNR (p = 0.534). No significant association between ΔBA and HDV-RNA dynamics at W48 was detected. After BLV discontinuation, median BA levels significantly dropped to normal ranges (18.9 μmol/L at last on-BLV assessment to 7.6 μmol/L after discontinuation; p = 0.028). On-treatment BA levels did neither associate with self-reported compliance nor with treatment-related adverse events.
CONCLUSION: Bulevirtide increases bile acid levels in most patients, but ΔBA does not predict virologic response or adverse events, nor does it reflect compliance to therapy. Bile acid level monitoring during and following bulevirtide treatment is thus, not advised for clinical practise.