ALBI Grade Enables Risk Stratification for Bleeding Events and Refines Prognostic Prediction in Advanced HCC Following Atezolizumab and Bevacizumab

Bernardo Stefanini; Claudia Angela Maria Fulgenzi; Bernhard Scheiner; James Korolewicz; Jaekyung Cheon; Naoshi Nishida; Celina Ang; Thomas U Marron; Y Linda Wu; Anwaar Saeed; Brooke Wietharn; Lorenza Rimassa; Angelo Pirozzi; Antonella Cammarota; Tiziana Pressiani; Matthias Pinter; Lorenz Balcar; Yi-Hsiang Huang; Aman Mehan; Samuel Phen; Caterina Vivaldi; Francesca Salani; Gianluca Masi; Dominik Bettinger; Arndt Vogel; Martin Schönlein; Johann von Felden; Kornelius Schulze; Henning Wege; Adel Samson; Peter R Galle; Masatoshi Kudo; Giulia Francesca Manfredi; Ciro Celsa; Nichola Awosika; Alessio Cortellini; Amit G Singal; Rohini Sharma; Hong Jae Chon; Francesco Tovoli; Fabio Piscaglia; David James Pinato; Antonio D'Alessio

doi:10.2147/JHC.S462701

ALBI Grade Enables Risk Stratification for Bleeding Events and Refines Prognostic Prediction in Advanced HCC Following Atezolizumab and Bevacizumab

J Hepatocell Carcinoma. 2025 Apr 4:12:671-683. doi: 10.2147/JHC.S462701. eCollection 2025.

Authors

Bernardo Stefanini^{1

2}, Claudia Angela Maria Fulgenzi^{1

3}, Bernhard Scheiner^{1

4}, James Korolewicz¹, Jaekyung Cheon⁵, Naoshi Nishida⁶, Celina Ang⁷, Thomas U Marron⁷, Y Linda Wu⁸, Anwaar Saeed⁹, Brooke Wietharn¹⁰, Lorenza Rimassa^{11

12}, Angelo Pirozzi^{11

12}, Antonella Cammarota¹², Tiziana Pressiani¹², Matthias Pinter⁴, Lorenz Balcar⁴, Yi-Hsiang Huang^{13

14}, Aman Mehan¹, Samuel Phen¹⁵, Caterina Vivaldi^{16

17}, Francesca Salani^{17

18}, Gianluca Masi^{16

17}, Dominik Bettinger¹⁹, Arndt Vogel^{20

21}, Martin Schönlein²², Johann von Felden²³, Kornelius Schulze²³, Henning Wege²³, Adel Samson²⁴, Peter R Galle²⁵, Masatoshi Kudo⁶, Giulia Francesca Manfredi^{1

26}, Ciro Celsa^{1

27}, Nichola Awosika¹, Alessio Cortellini^{1

3}, Amit G Singal¹⁵, Rohini Sharma¹, Hong Jae Chon⁵, Francesco Tovoli^{2

28}, Fabio Piscaglia^{2

28}, David James Pinato^#^{1

26}, Antonio D'Alessio^#¹

Affiliations

¹ Department of Surgery and Cancer, Imperial College London, London, UK.
² Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
³ Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
⁵ Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
⁶ Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
⁷ Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.
⁸ Division of hematology/oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
⁹ Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh (UPMC), Pittsburgh, PA, USA.
¹⁰ Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS, USA.
¹¹ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
¹² Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy.
¹³ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁴ Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
¹⁵ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁶ Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
¹⁷ Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
¹⁸ Sant`Anna School of Advanced Studies, Pisa, Italy.
¹⁹ Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
²⁰ Hannover Medical School, Hannover, Germany.
²¹ Longo Family Chair in Liver Cancer Research, Division of Gastroenterology and Hepatology, Toronto General Hospital, Medical Oncology, Princess Margaret Cancer Centre, Schwartz Reisman Liver Research Centre, Toronto, Canada.
²² Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²³ Department of Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁴ Leeds Institute of Medical Research at St James's (LIMR), School of Medicine, Faculty of Medicine and Health, University of Leeds, St James's University Hospital, Leeds, UK.
²⁵ University Medical Center Mainz, I. Department. of Internal Medicine, Mainz, Germany.
²⁶ Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
²⁷ Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
²⁸ Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.

^# Contributed equally.

Abstract

Background and aims: Atezolizumab and bevacizumab (A+B) are recommended for treating unresectable hepatocellular carcinoma (HCC). Although highly effective, A+B can lead to potentially life-threatening adverse events including bleeding. We investigated whether albumin-bilirubin (ALBI) grade identifies patients with a higher risk of bleeding and its impact on prognosis than the Child-Pugh (CP) score.

Methods: We performed a multicenter retrospective study of 15 tertiary referral centers that consecutively treated patients with A+B. We analyzed the association between the ALBI grade and gastrointestinal bleeding using the χ2 test. Overall survival (OS) stratified by ALBI was estimated using the Kaplan-Meier method and the predictive value for the 6-months OS landmark with ROC curves.

Results: Of the 368 patients included in the analysis, 163 (44.3%), 192 (52.2%) and 13 (3.5%) had ALBI 1, ALBI 2, and ALBI 3, respectively. ALBI grade was associated with a 3-fold increase in bleeding risk (3.1% in ALBI 1 vs 10.2% in ALBI 2/3, p=0.008). Among 192 patients with pre-treatment EGD, G2 and G3 varices were associated with an increased risk of bleeding, whereas G1 varices had a similar risk as no varices. Patients with ALBI 1 achieved a longer median OS (not reached; 95% CI, 24.9-33.7), than ALBI 2 (9.7 months; 95% CI, 7.0-12.3) or ALBI 3 (5.6 months; 95% CI, 0.1-12.0). ALBI outperformed the CP score for predicting 6-month OS with an AUC 0.79 of ALBI versus 0.71 for the CP score (p=0.01).

Conclusion: A Higher ALBI grade was associated with an increased risk of gastrointestinal bleeding after receiving A+B, and outperformed the CP score in predicting worse survival.

Keywords: ALBI; bleeding risk; hepatocellular carcinoma; systemic treatment.

Grants and funding

A D’Alessio is supported by the National Institute for Health Research (NIHR) Imperial BRC, by grant funding from the European Association for the Study of the Liver (2021 Andrew Burroughs Fellowship) and from Cancer Research UK (RCCPDB- Nov21/100008). DJ Pinato is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416), the Associazione Italiana per la Ricerca sul Cancro (AIRC MFAG 25697) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT), the Foundation for Liver Research (Small Grant Scheme), and infrastructural support by the Imperial Experimental Cancer Medicine Centre and the NIHR Imperial Biomedical Research Centre.