Author information

¹Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.

²Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Italy.

³Department of Economics Business and Statistics, University of Palermo, Italy.

⁴Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Italy.

⁵Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

⁶Department of Translational Medicine, Università Del Piemonte Orientale, Novara, Italy.

⁷Department of Medical and Surgical Sciences, University of Bologna, Italy.

⁸Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

⁹University Medical Center Mainz, Department of Internal Medicine I, Mainz, Germany.

¹⁰Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

¹¹Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

¹²Unit of Medical Oncology 2, Azienda Ospedaliero- Universitaria Pisana, Pisa, Italy.

¹³Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, Kansas, USA.

¹⁴Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.

¹⁵College of Medicine, Chang Gung University, Taoyuan, Taiwan.

¹⁶Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy.

¹⁷Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy.

¹⁸Section of General Medicine C, Medicine Department, University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.

¹⁹Liver Unit, Medicine Department, University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.

²⁰Section 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.

²¹Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy.

²²Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.

²³Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.

²⁴Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

²⁵Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

²⁶Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.

²⁷Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

²⁸Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

²⁹Section of Gastroenterology, Hepatology & Nutrition, the University of Chicago Medicine 5841 S. Maryland Ave, 60637 Chicago, IL, USA.

³⁰Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

³¹Hannover Medical School, Hannover, Germany.

³²Longo 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.

³³Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City.

³⁴Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

³⁵Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

³⁶Operative Research Unit of Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200 - 00128 Roma, Italy.

Abstract

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

Approachresults: From the AB-real observational study(n=898), we accrued 571 patients with advanced/unresectable HCC, Child-Pugh A class treated with frontline atezolizumab+bevacizumab(AB). Hepatic decompensation and tumour progression during follow-up were studied in relationship to patients' OS using 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 tumour progression without decompensation and 94(16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation(hazard ratio[HR] 19.04, 95%CI 9.75-37.19), HCC 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. Pre-treatment ALBI grade 2/3(subdistribution HR [sHR] 3.35, 95%CI 1.98-5.67) was independently associated with decompensation, whereas viral aetiology was protective(sHR 0.55, 95%CI 0.34-0.87). Among patients with viral aetiology, effective antiviral treatment was significantly associated with 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 non-viral aetiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with non-viral aetiologies and the importance of multi-disciplinary management to maximise OS.