Hepatic decompensation is the major driver of mortality in patients with HCC treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment

Ciro Celsa; Giuseppe Cabibbo; Claudia Angela Maria Fulgenzi; Salvatore Battaglia; Marco Enea; Bernhard Scheiner; Antonio D'Alessio; Giulia F Manfredi; Bernardo Stefanini; Naoshi Nishida; Peter R Galle; Kornelius Schulze; Henning Wege; Roberta Ciccia; Wei-Fan Hsu; Caterina Vivaldi; Brooke Wietharn; Ryan Po-Ting Lin; Angelo Pirozzi; Tiziana Pressiani; Andrea Dalbeni; Leonardo A Natola; Alessandra Auriemma; Cristina Rigamonti; Michela Burlone; Alessandro Parisi; Yi-Hsiang Huang; Pei-Chang Lee; Celina Ang; Thomas U Marron; Matthias Pinter; Jaekyung Cheon; Samuel Phen; Amit G Singal; Anuhya Gampa; Anjana Pillai; Natascha Roehlen; Robert Thimme; Arndt Vogel; Noha Soror; Susanna Ulahannan; Rohini Sharma; David Sacerdoti; Mario Pirisi; Lorenza Rimassa; Chun-Yen Lin; Anwaar Saeed; Gianluca Masi; Martin Schönlein; Johann von Felden; Masatoshi Kudo; Alessio Cortellini; Hong Jae Chon; Calogero Cammà; David James Pinato

doi:10.1097/HEP.0000000000001026

Hepatic decompensation is the major driver of mortality in patients with HCC treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment

Hepatology. 2024 Jul 19. doi: 10.1097/HEP.0000000000001026. Online ahead of print.

Authors

Ciro Celsa^{1

2}, Giuseppe Cabibbo², Claudia Angela Maria Fulgenzi¹, Salvatore Battaglia³, Marco Enea⁴, Bernhard Scheiner⁵, Antonio D'Alessio^{1

6}, Giulia F Manfredi^{1

6}, Bernardo Stefanini^{1

7}, Naoshi Nishida⁸, Peter R Galle⁹, Kornelius Schulze¹⁰, Henning Wege¹⁰, Roberta Ciccia², Wei-Fan Hsu¹¹, Caterina Vivaldi¹², Brooke Wietharn¹³, Ryan Po-Ting Lin^{14

15}, Angelo Pirozzi^{16

17}, Tiziana Pressiani¹⁷, Andrea Dalbeni^{18

19}, Leonardo A Natola¹⁹, Alessandra Auriemma²⁰, Cristina Rigamonti⁶, Michela Burlone⁶, Alessandro Parisi²¹, Yi-Hsiang Huang^{22

23

24}, Pei-Chang Lee^{23

25}, Celina Ang²⁶, Thomas U Marron²⁷, Matthias Pinter⁵, Jaekyung Cheon²⁷, Samuel Phen²⁸, Amit G Singal²⁸, Anuhya Gampa²⁹, Anjana Pillai²⁹, Natascha Roehlen³⁰, Robert Thimme³⁰, Arndt Vogel^{31

32}, Noha Soror³³, Susanna Ulahannan³³, Rohini Sharma¹, David Sacerdoti¹⁹, Mario Pirisi⁶, Lorenza Rimassa^{16

17}, Chun-Yen Lin^{14

15}, Anwaar Saeed³⁴, Gianluca Masi¹², Martin Schönlein³⁵, Johann von Felden¹⁰, Masatoshi Kudo⁸, Alessio Cortellini^{1

36}, Hong Jae Chon²⁷, Calogero Cammà², David James Pinato^{1

6}

Affiliations

¹ Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK.
² Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy.
³ Department of Economics Business and Statistics, University of Palermo, Palermo, Italy.
⁴ Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy.
⁵ Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
⁶ Department of Translational Medicine, Università Del Piemonte Orientale, Novara, Italy.
⁷ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁸ Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan.
⁹ Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.
¹⁰ Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan.
¹² Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
¹³ Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, Kansas, USA.
¹⁴ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
¹⁵ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁶ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
¹⁷ Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁸ Section of General Medicine C, Medicine Department, University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.
¹⁹ Liver Unit, Medicine Department, University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.
²⁰ Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.
²¹ Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy.
²² Department of Medicine, Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.
²³ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
²⁴ Department of Medicine, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
²⁵ Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
²⁶ Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, New York, USA.
²⁷ Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
²⁸ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
²⁹ Section of Gastroenterology, Hepatology & Nutrition, The University of Chicago Medicine, Chicago, Illinois, USA.
³⁰ Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, University of Freiburg, Freiburg, Germany.
³¹ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
³² Longo Family Chair in Liver Cancer Research, Division of Gastroenterology and Hepatology, Department of Medicine, Toronto General Hospital, Medical Oncology, Princess Margaret Cancer Centre, Schwartz Reisman Liver Research Centre, Toronto, Canada.
³³ Department of Internal Medicine, Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA.
³⁴ Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
³⁵ Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁶ Operative Research Unit of Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy.

PMID: 39028886
DOI: 10.1097/HEP.0000000000001026

Abstract

Background and aims: Unlike other malignancies, hepatic functional reserve competes with tumor progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumor progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients.

Approach and results: From the AB-real observational study (n = 898), we accrued 571 patients with advanced/unresectable hepatocellular carcinoma, Child-Pugh A class treated with frontline atezolizumab + bevacizumab (AB). Hepatic decompensation and tumor progression during follow-up were studied in relationship to patients' OS using a time-dependent Cox model. Baseline characteristics were evaluated as predictors of decompensation in competing risks analysis. During a median follow-up of 11.0 months (95% CI: 5.1-19.7), 293 patients (51.3%) developed tumor progression without decompensation, and 94 (16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation (HR: 19.04, 95% CI: 9.75-37.19), hepatocellular carcinoma progression (HR: 9.91, 95% CI: 5.85-16.78), albumin-bilirubin (ALBI) grade 2/3 (HR: 2.16, 95% CI: 1.69-2.77), and number of nodules >3(HR: 1.63, 95% CI: 1.28-2.08) were independently associated with OS. Pretreatment ALBI grade 2/3 (subdistribution hazard ratio [sHR]: 3.35, 95% CI: 1.98-5.67) was independently associated with decompensation, whereas viral etiology was protective (sHR: 0.55, 95% CI: 0.34-0.87). Among patients with viral etiology, effective antiviral treatment was significantly associated with a lower risk of decompensation (sHR: 0.48, 95% CI: 0.25-0.93).

Conclusions: Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI >1 and nonviral etiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with nonviral etiologies and the importance of multidisciplinary management to maximize OS.