Hepatic decompensation is the major driver of mortality in patients with HCC treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment-Reference-Cited by-同舟云学术

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

Published:2024-07-19 Issue: Volume: Page:
ISSN:0270-9139
Container-title:Hepatology
language:en
Short-container-title:

Author:

Celsa Ciro¹²^ORCID,Cabibbo Giuseppe²^ORCID,Fulgenzi Claudia Angela Maria¹,Battaglia Salvatore³,Enea Marco⁴,Scheiner Bernhard⁵,D’Alessio Antonio¹⁶,Manfredi Giulia F.¹⁶,Stefanini Bernardo¹⁷,Nishida Naoshi⁸,Galle Peter R.⁹,Schulze Kornelius¹⁰,Wege Henning¹⁰,Ciccia Roberta²,Hsu Wei-Fan¹¹,Vivaldi Caterina¹²,Wietharn Brooke¹³,Lin Ryan Po-Ting¹⁴¹⁵,Pirozzi Angelo¹⁶¹⁷,Pressiani Tiziana¹⁷,Dalbeni Andrea¹⁸¹⁹,Natola Leonardo A.¹⁹,Auriemma Alessandra²⁰,Rigamonti Cristina⁶,Burlone Michela⁶,Parisi Alessandro²¹,Huang Yi-Hsiang²²²³²⁴,Lee Pei-Chang²³²⁵,Ang Celina²⁶,Marron Thomas U.²⁷,Pinter Matthias⁵,Cheon Jaekyung²⁷,Phen Samuel²⁸,Singal Amit G.²⁸,Gampa Anuhya²⁹,Pillai Anjana²⁹,Roehlen Natascha³⁰,Thimme Robert³⁰,Vogel Arndt³¹³²,Soror Noha³³,Ulahannan Susanna³³,Sharma Rohini¹,Sacerdoti David¹⁹,Pirisi Mario⁶,Rimassa Lorenza¹⁶¹⁷,Lin Chun-Yen¹⁴¹⁵,Saeed Anwaar³⁴,Masi Gianluca¹²,Schönlein Martin³⁵,von Felden Johann¹⁰,Kudo Masatoshi⁸,Cortellini Alessio¹³⁶,Chon Hong Jae²⁷,Cammà Calogero²,Pinato David James¹⁶^ORCID

Affiliation:

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

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference40 articles.

1. Hepatocellular carcinoma;Vogel;Lancet,2022

2. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update;Reig;J Hepatol,2022

3. Personalised management of patients with hepatocellular carcinoma: A multiparametric therapeutic hierarchy concept;Vitale;Lancet Oncol,2023

4. Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies;D’Amico;J Hepatol,2006

5. The clinical course of cirrhosis. Population based studies and the need of personalized medicine;D’Amico;J Hepatol,2014