전홍재 (차의과학대학교 분당차병원)

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조회198

차의과학대학교 분당차병원

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Hepatology, Jul 19 2024, | https://doi.org/10.1097/HEP.0000000000001026 Hepatic decompensation is the major driver of mortality in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment

Celsa, Ciro^1,2; Cabibbo, Giuseppe²; Fulgenzi, Claudia Angela Maria¹; Battaglia, Salvatore³; Enea, Marco⁴; Scheiner, Bernhard⁵; D’Alessio, Antonio^1,6; Manfredi, Giulia F.^1,6; Stefanini, Bernardo^1,7; Nishida, Naoshi⁸; Galle, Peter R.⁹; Schulze, Kornelius¹⁰; Wege, Henning¹⁰; Ciccia, Roberta²; Hsu, Wei-Fan1¹; Vivaldi, Caterina¹²; Wietharn, Brooke¹³; Lin, Ryan Po-Ting^14,15; Pirozzi, Angelo^16,17; Pressiani, Tiziana¹⁷; Dalbeni, Andrea^18,19; Natola, Leonardo A.¹⁹; Auriemma, Alessandra²⁰; Rigamonti, Cristina⁶; Burlone, Michela⁶; Parisi, Alessandro²¹; Huang, Yi-Hsiang^22,23,24; Lee, Pei-Chang^23,25; Ang, Celina²⁶; Marron, Thomas U.²⁷; Pinter, Matthias⁵; Cheon, Jaekyung²⁷; Phen, Samuel²⁸; Singal, Amit G²⁸; Gampa, Anuhya²⁹; Pillai, Anjana²⁹; Roehlen, Natascha³⁰; Thimme, Robert³⁰; Vogel, Arndt^31,32; Soror, Noha³³; Ulahannan, Susanna³³; Sharma, Rohini¹; Sacerdoti, David¹⁹; Pirisi, Mario⁶; Rimassa, Lorenza^16,17; Lin, Chun-Yen^14,15; Saeed, Anwaar³⁴; Masi, Gianluca¹²; Schönlein, Martin³⁵; von Felden, Johann¹⁰; Kudo, Masatoshi⁸; Cortellini, Alessio^1,36; Chon, Hong Jae²⁷; Cammà, Calogero²; Pinato, David James^1,6

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

Ciro Celsa and Giuseppe Cabibbo: These authors share co-first authorship

Hong Jae Chon, Calogero Cammà and David James Pinato: These authors share co-last authorship

Correspondence Calogero Cammà, MD, PhD, David J. Pinato, MD MRes MRCP PhD

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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-08-12)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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