von Willebrand Factor and ADAMTS13 Predict Therapeutic Efficacy and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Atezolizumab-Bevacizumab.
- 1Department of Gastroenterology Nara Medical University Nara Japan.
Abstract
Aims
Atezolizumab combined with bevacizumab (AB therapy) is a standard first-line treatment for advanced hepatocellular carcinoma (HCC). However, clinically useful biomarkers for predicting therapeutic efficacy and severe adverse events (AEs) remain limited. Beyond its role in thrombosis, ADAMTS13-von Willebrand factor (VWF) axis is increasingly recognized for its involvement in angiogenesis and immune modulation. This study aimed to investigate the clinical significance of the ADAMTS13-VWF axis in patients receiving AB therapy.Methods
A total of 58 patients with advanced HCC treated with AB therapy were enrolled. Plasma VWF antigen (VWF:Ag) and ADAMTS13 activity (ADAMTS13:AC) were measured before treatment initiation. Therapeutic efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST (mRECIST), while safety was assessed according to Common Terminology Criteria for AEs version 5.0.Results
Multivariate analyses identified lower baseline VWF:Ag (< 180%) and ADAMTS13:AC (≤ 60%) as independent predictors of superior therapeutic efficacy according to both RECIST and mRECIST criteria. Patients with low VWF:Ag (< 180%) and ADAMTS13:AC (≤ 60%) exhibited significantly prolonged overall survival. Lower baseline VWF:Ag to ADAMTS13:AC (VWF/ADAMTS13) ratios (< 3) were independently associated with severe AEs (Grade ≥ 3). Plasma VWF:Ag and ADAMTS13:AC levels did not significantly change after AB therapy.Conclusion
Baseline VWF:Ag and ADAMTS13:AC independently predict therapeutic efficacy, whereas the baseline VWF/ADAMTS13 ratio independently predicts severe AEs in patients with HCC receiving AB therapy. These biomarkers may help optimize patient selection and manage treatment-related toxicities by reflecting tumor angiogenic activity and host immune status.
Related
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- Acute colonic variceal bleeding treated with coil-assisted retrograde transvenous obliteration following atezolizumab-bevacizumab therapy for advanced hepatocellular carcinoma: A case report.
- Real-world evidence for atezolizumab with bevacizumab for unresectable hepatocellular carcinoma: a multicentre UK Midlands cohort
- Prognostic Significance of Response Dynamics in Atezolizumab plus Bevacizumab-Treated Hepatocellular Carcinoma: A Multicenter Real-World Validation Study.
- Baseline Host Biomarkers and Six-Month Sustained Drug-Free Status After Atezolizumab–Bevacizumab for Hepatocellular Carcinoma: Exploratory Clinical Stratification Using PAN-DF Score
BibTeX
@article{nishimura2026willebrand,
title = {{von Willebrand Factor and ADAMTS13 Predict Therapeutic Efficacy and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Atezolizumab-Bevacizumab.}},
author = {Naoki Nishimura and Hiroaki Takaya and Tadashi Namisaki and Yusuke Komeda and Satoshi Iwai and Akihiko Shibamoto and Yuki Tsuji and Yukihisa Fujinaga and Koh Kitagawa and Shinya Sato and Norihisa Nishimura and Kosuke Kaji and Hitoshi Yoshiji},
journal = {JGH open : an open access journal of gastroenterology and hepatology},
year = {2026},
month = oct,
doi = {10.1002/jgh3.70484},
url = {https://europepmc.org/article/MED/42948561},
note = {CC BY},
}
RIS
TY - JOUR
TI - von Willebrand Factor and ADAMTS13 Predict Therapeutic Efficacy and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Atezolizumab-Bevacizumab.
AU - Naoki Nishimura
AU - Hiroaki Takaya
AU - Tadashi Namisaki
AU - Yusuke Komeda
AU - Satoshi Iwai
AU - Akihiko Shibamoto
AU - Yuki Tsuji
AU - Yukihisa Fujinaga
AU - Koh Kitagawa
AU - Shinya Sato
AU - Norihisa Nishimura
AU - Kosuke Kaji
AU - Hitoshi Yoshiji
PY - 2026
DA - 2026/10/27
JO - JGH open : an open access journal of gastroenterology and hepatology
DO - 10.1002/jgh3.70484
UR - https://europepmc.org/article/MED/42948561
AB - Aims Atezolizumab combined with bevacizumab (AB therapy) is a standard first-line treatment for advanced hepatocellular carcinoma (HCC). However, clinically useful biomarkers for predicting therapeutic efficacy and severe adverse events (AEs) remain limited. Beyond its role in thrombosis, ADAMTS13-von Willebrand factor (VWF) axis is increasingly recognized for its involvement in angiogenesis and immune modulation. This study aimed to investigate the clinical significance of the ADAMTS13-VWF axis in patients receiving AB therapy.Methods A total of 58 patients with advanced HCC treated with AB therapy were enrolled. Plasma VWF antigen (VWF:Ag) and ADAMTS13 activity (ADAMTS13:AC) were measured before treatment initiation. Therapeutic efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST (mRECIST), while safety was assessed according to Common Terminology Criteria for AEs version 5.0.Results Multivariate analyses identified lower baseline VWF:Ag (< 180%) and ADAMTS13:AC (≤ 60%) as independent predictors of superior therapeutic efficacy according to both RECIST and mRECIST criteria. Patients with low VWF:Ag (< 180%) and ADAMTS13:AC (≤ 60%) exhibited significantly prolonged overall survival. Lower baseline VWF:Ag to ADAMTS13:AC (VWF/ADAMTS13) ratios (< 3) were independently associated with severe AEs (Grade ≥ 3). Plasma VWF:Ag and ADAMTS13:AC levels did not significantly change after AB therapy.Conclusion Baseline VWF:Ag and ADAMTS13:AC independently predict therapeutic efficacy, whereas the baseline VWF/ADAMTS13 ratio independently predicts severe AEs in patients with HCC receiving AB therapy. These biomarkers may help optimize patient selection and manage treatment-related toxicities by reflecting tumor angiogenic activity and host immune status.
SN - 2397-9070
ER -