PMID- 37972660
OWN - NLM
STAT- MEDLINE
DCOM- 20240219
LR  - 20240219
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 80
IP  - 3
DP  - 2024 Mar
TI  - Characteristics and outcomes of immunotherapy-related liver injury in patients 
      with hepatocellular carcinoma versus other advanced solid tumours.
PG  - 431-442
LID - S0168-8278(23)05272-8 [pii]
LID - 10.1016/j.jhep.2023.10.040 [doi]
AB  - BACKGROUND & AIMS: Immune-related liver injury (irLI) is commonly observed in 
      patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed 
      to compare the incidence, clinical characteristics, and outcomes of irLI between 
      patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid 
      tumours. METHODS: Two separate cohorts were included: 375 patients with 
      advanced/unresectable HCC, Child-Pugh A class treated with first-line 
      atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 
      459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre 
      study. IrLI was defined as a treatment-related increase of aminotransferase 
      levels after exclusion of alternative aetiologies of liver injury. The incidence 
      of irLI was adjusted for the duration of treatment exposure. RESULTS: In patients 
      with HCC, the incidence of any grade irLI was 11.4% over a median treatment 
      exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a 
      median treatment exposure of 12.4 months (95% CI 11.1-14.0). 
      Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in 
      patients with HCC and 2.1 per 100-patient-years in patients with other solid 
      tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. 
      Among patients who developed irLI, systemic corticosteroids were administered in 
      16.3% of patients with HCC and 75.0% of those without HCC (p <0.001), and irLI 
      resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients 
      with HCC, rates of hepatic decompensation and treatment discontinuation due to 
      irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only 
      in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96). CONCLUSIONS: Despite 
      higher incidence and earlier onset, irLI in patients with HCC is characterised by 
      higher rates of remission and lower requirement for corticosteroid therapy (vs. 
      irLI in other solid tumours), low risk of hepatic decompensation and treatment 
      discontinuation, not negatively affecting oncological outcomes. IMPACT AND 
      IMPLICATIONS: Immune-related liver injury (irLI) is common in patients with 
      cancer receiving immune checkpoint inhibitors (ICIs), but whether irLI is more 
      frequent or it is associated with a worse clinical course in patients with 
      hepatocellular carcinoma (HCC), compared to other tumours, is not known. Herein, 
      we compared characteristics and outcomes of irLI in two prospective cohorts 
      including patients treated with ICIs for HCC or for other oncological 
      indications. irLI is significantly more common and it occurs earlier in patients 
      with HCC, also after adjustment for duration of treatment exposure. However, 
      outcomes of patients with HCC who developed irLI are not negatively affected in 
      terms of requirement for corticosteroid therapy, hepatic decompensation, 
      treatment discontinuation and overall survival.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Celsa, Ciro
AU  - Celsa C
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Gastroenterology and Hepatology Unit, Department of 
      Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, 
      University of Palermo, Italy.
FAU - Cabibbo, Giuseppe
AU  - Cabibbo G
AD  - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & 
      Child Care, Internal Medicine & Medical Specialties, University of Palermo, 
      Italy.
FAU - Fulgenzi, Claudia A M
AU  - Fulgenzi CAM
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Operative Research Unit of Oncology, Fondazione 
      Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200 - 00128 
      Roma, Italy.
FAU - Scheiner, Bernhard
AU  - Scheiner B
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Division of Gastroenterology and Hepatology, 
      Department of Internal Medicine III, Medical University of Vienna, Vienna, 
      Austria.
FAU - D'Alessio, Antonio
AU  - D'Alessio A
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Division of Oncology, Department of Translational 
      Medicine, University of Piemonte Orientale, Novara, Italy.
FAU - Manfredi, Giulia F
AU  - Manfredi GF
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Division of Oncology, Department of Translational 
      Medicine, University of Piemonte Orientale, Novara, Italy.
FAU - Nishida, Naoshi
AU  - Nishida N
AD  - Department of Gastroenterology and Hepatology, Kindai University Faculty of 
      Medicine, Osaka, Japan.
FAU - Ang, Celina
AU  - Ang C
AD  - Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, 
      Mount Sinai Hospital, New York, NY, USA.
FAU - Marron, Thomas U
AU  - Marron TU
AD  - Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, 
      Mount Sinai Hospital, New York, NY, USA.
FAU - Saeed, Anwaar
AU  - Saeed A
AD  - Department of Medicine, Division of Hematology & Oncology, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Wietharn, Brooke
AU  - Wietharn B
AD  - Department of Medicine, Division of Medical Oncology, Kansas University Cancer 
      Center, Kansas City, Kansas, USA.
FAU - Pinter, Matthias
AU  - Pinter M
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine III, 
      Medical University of Vienna, Vienna, Austria.
FAU - Cheon, Jaekyung
AU  - Cheon J
AD  - Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, 
      CHA University, Seongnam, South Korea.
FAU - Huang, Yi-Hsiang
AU  - Huang YH
AD  - Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan; 
      Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, 
      Taipei, Taiwan; Institute of Clinical Medicine, Faculty of Medicine, National 
      Yang Ming Chiao Tung University, Taipei, Taiwan.
FAU - Lee, Pei-Chang
AU  - Lee PC
AD  - Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, 
      Taipei, Taiwan; Faculty of Medicine, National Yang Ming Chiao Tung University, 
      Taipei, Taiwan.
FAU - Phen, Samuel
AU  - Phen S
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Gampa, Anuhya
AU  - Gampa A
AD  - Section of Gastroenterology, Hepatology & Nutrition, the University of Chicago 
      Medicine 5841 S. Maryland Ave, 60637 Chicago, IL, USA.
FAU - Pillai, Anjana
AU  - Pillai A
AD  - Unit of Medical Oncology 2, Azienda Ospedaliero- Universitaria Pisana, Pisa, 
      Italy.
FAU - Vivaldi, Caterina
AU  - Vivaldi C
AD  - Scuola Superiore Sant'Anna Pisa, interdisciplinary research center "Health 
      Science", Pisa, Italy.
FAU - Salani, Francesca
AU  - Salani F
AD  - Unit of Medical Oncology 2, Azienda Ospedaliero- Universitaria Pisana, Pisa, 
      Italy; Scuola Superiore Sant'Anna Pisa, interdisciplinary research center "Health 
      Science", Pisa, Italy.
FAU - Masi, Gianluca
AU  - Masi G
AD  - Unit of Medical Oncology 2, Azienda Ospedaliero- Universitaria Pisana, Pisa, 
      Italy.
FAU - Roehlen, Natascha
AU  - Roehlen N
AD  - Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and 
      Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, 
      University of Freiburg, Freiburg, Germany.
FAU - Thimme, Robert
AU  - Thimme R
AD  - Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and 
      Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, 
      University of Freiburg, Freiburg, Germany.
FAU - Vogel, Arndt
AU  - Vogel A
AD  - Hannover Medical School, Hannover, Germany; 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.
FAU - Schonlein, Martin
AU  - Schonlein M
AD  - Department of Oncology, Hematology and Bone Marrow Transplantation with Section 
      of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - von Felden, Johann
AU  - von Felden J
AD  - Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Schulze, Kornelius
AU  - Schulze K
AD  - Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Wege, Henning
AU  - Wege H
AD  - Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Galle, Peter R
AU  - Galle PR
AD  - University Medical Center Mainz, Department of Internal Medicine I, Mainz, 
      Germany.
FAU - Kudo, Masatoshi
AU  - Kudo M
AD  - Department of Gastroenterology and Hepatology, Kindai University Faculty of 
      Medicine, Osaka, Japan.
FAU - Rimassa, Lorenza
AU  - Rimassa L
AD  - Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 
      4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, 
      Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 
      Rozzano, Milan, Italy.
FAU - Singal, Amit G
AU  - Singal AG
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - El Tomb, Paul
AU  - El Tomb P
AD  - Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of 
      Oklahoma, Oklahoma City.
FAU - Ulahannan, Susanna
AU  - Ulahannan S
AD  - Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of 
      Oklahoma, Oklahoma City.
FAU - Parisi, Alessandro
AU  - Parisi A
AD  - Department of Oncology, Universita Politecnica delle Marche, Azienda 
      Ospedaliero-Universitaria delle Marche, 60126 Ancona, Italy.
FAU - Chon, Hong Jae
AU  - Chon HJ
AD  - Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, 
      CHA University, Seongnam, South Korea.
FAU - Hsu, Wei-Fan
AU  - Hsu WF
AD  - Center for Digestive Medicine, Department of Internal Medicine, China Medical 
      University Hospital, Taichung, Taiwan.
FAU - Stefanini, Bernardo
AU  - Stefanini B
AD  - Department of Medical and Surgical Sciences, University of Bologna, Italy.
FAU - Verzoni, Elena
AU  - Verzoni E
AD  - SS. Oncologia Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, 
      Milano, Italy.
FAU - Giusti, Raffaele
AU  - Giusti R
AD  - Medical Oncology Unit, Sant'Andrea Hospital, Roma, Italy.
FAU - Veccia, Antonello
AU  - Veccia A
AD  - Medical Oncology, Santa Chiara Hospital, Trento, Italy.
FAU - Catino, Annamaria
AU  - Catino A
AD  - Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, 
      Italy.
FAU - Aprile, Giuseppe
AU  - Aprile G
AD  - Department of Oncology, San Bortolo General Hospital, Vicenza, Italy.
FAU - Guglielmini, Pamela Francesca
AU  - Guglielmini PF
AD  - SC Oncologia, AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy.
FAU - Di Napoli, Marilena
AU  - Di Napoli M
AD  - UC Oncologia Medica Uro-Ginecologica, Istituto Nazionale Tumori "Fondazione G. 
      Pascale", IRCCS, Napoli, Italy.
FAU - Ermacora, Paola
AU  - Ermacora P
AD  - Dipartimento di Oncologia, Presidio Ospedaliero Universitario Santa Maria della 
      Misericordia, Azienda sanitaria universitaria Integrata Friuli Centrale, Udine, 
      Italy.
FAU - Antonuzzo, Lorenzo
AU  - Antonuzzo L
AD  - Medical Oncology Unit, University Hospital Careggi, Firenze, Italy.
FAU - Rossi, Ernesto
AU  - Rossi E
AD  - Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, 
      Italy.
FAU - Verderame, Francesco
AU  - Verderame F
AD  - Oncology Department, Ospedali Riuniti Villa Sofia Cervello, Palermo, Italy.
FAU - Zustovich, Fable
AU  - Zustovich F
AD  - UOC Oncologia di Belluno, Dipartimento di Oncologia Clinica, AULSS 1 Dolomiti, 
      Ospedale S.Martino, Belluno, Italy.
FAU - Ficorella, Corrado
AU  - Ficorella C
AD  - Department of Biotechnological and Applied Clinical Sciences, St Salvatore 
      Hospital, University of L'Aquila, L'Aquila, Italy.
FAU - Di Pietro, Francesca Romana
AU  - Di Pietro FR
AD  - U.O.C. Oncologia, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Roma, Italy.
FAU - Battelli, Nicola
AU  - Battelli N
AD  - UOC Oncologia, Ospedale Generale Provinciale di Macerata, ASUR Marche Area Vasta 
      3, Macerata, Italy.
FAU - Negrini, Giorgia
AU  - Negrini G
AD  - Medical Oncology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy.
FAU - Grossi, Francesco
AU  - Grossi F
AD  - Medical Oncology Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy.
FAU - Bordonaro, Roberto
AU  - Bordonaro R
AD  - Medical Oncology Unit, ARNAS Garibaldi, Catania, Italy.
FAU - Pipitone, Stefania
AU  - Pipitone S
AD  - Medical Oncology Unit, University Hospital of Modena e Reggio Emilia, Italy.
FAU - Banzi, Maria
AU  - Banzi M
AD  - Medical Oncology Unit, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
FAU - Ricciardi, Serena
AU  - Ricciardi S
AD  - Medical Oncology, San Camillo Forlanini Hospital, Roma, Italy.
FAU - Laera, Letizia
AU  - Laera L
AD  - Medical Oncology, Ospedale Generale Regionale F Miulli, Acquaviva delle Fonti, 
      Puglia, Italy.
FAU - Russo, Antonio
AU  - Russo A
AD  - Dipartimento di Discipline Chirurgiche, Oncologiche e Stomatologiche, Universita 
      degli Studi di Palermo, Palermo, Italy.
FAU - De Giorgi, Ugo
AU  - De Giorgi U
AD  - Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la 
      Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
FAU - Cavanna, Luigi
AU  - Cavanna L
AD  - Oncologia Medica, ASL di Piacenza, Piacenza, Italy.
FAU - Soraru, Mariella
AU  - Soraru M
AD  - Medical Oncology, Camposampiero Hospital, AULSS 6 Euganea, Padova, Italy.
FAU - Montesarchio, Vincenzo
AU  - Montesarchio V
AD  - UOC Oncologia, Ospedale Monaldi, Azienda Ospedaliera Specialistica dei Colli, 
      Napoli, Italy.
FAU - Bordi, Paola
AU  - Bordi P
AD  - Medical Oncology Unit, Medicine and Surgery Department, University of Parma, 
      Parma, Italy.
FAU - Brunetti, Leonardo
AU  - Brunetti L
AD  - Operative Research Unit of Oncology, Fondazione Policlinico Universitario Campus 
      Bio-Medico, Via Alvaro del Portillo, 200 - 00128 Roma, Italy.
FAU - Pinto, Carmine
AU  - Pinto C
AD  - Medical Oncology Unit, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
FAU - Bersanelli, Melissa
AU  - Bersanelli M
AD  - Medical Oncology Unit, Medicine and Surgery Department, University of Parma, 
      Parma, Italy.
FAU - Camma, Calogero
AU  - Camma C
AD  - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & 
      Child Care, Internal Medicine & Medical Specialties, University of Palermo, 
      Italy.
FAU - Cortellini, Alessio
AU  - Cortellini A
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Operative Research Unit of Oncology, Fondazione 
      Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200 - 00128 
      Roma, Italy.
FAU - Pinato, David J
AU  - Pinato DJ
AD  - Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du 
      Cane Road, W120HS London, UK; Division of Oncology, Department of Translational 
      Medicine, University of Piemonte Orientale, Novara, Italy. Electronic address: 
      david.pinato@imperial.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20231115
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Adrenal Cortex Hormones)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Hepatocellular/drug therapy
MH  - Immune Checkpoint Inhibitors/adverse effects
MH  - Prospective Studies
MH  - *Liver Neoplasms/drug therapy/epidemiology
MH  - Immunotherapy/adverse effects
MH  - Adrenal Cortex Hormones
OTO - NOTNLM
OT  - atezolizumab plus bevacizumab
OT  - hepatocellular carcinoma
OT  - hepatotoxicity
OT  - immune-related liver injury
OT  - immunotherapy
EDAT- 2023/11/17 15:23
MHDA- 2024/02/19 06:42
CRDT- 2023/11/16 19:24
PHST- 2023/08/29 00:00 [received]
PHST- 2023/10/26 00:00 [revised]
PHST- 2023/10/30 00:00 [accepted]
PHST- 2024/02/19 06:42 [medline]
PHST- 2023/11/17 15:23 [pubmed]
PHST- 2023/11/16 19:24 [entrez]
AID - S0168-8278(23)05272-8 [pii]
AID - 10.1016/j.jhep.2023.10.040 [doi]
PST - ppublish
SO  - J Hepatol. 2024 Mar;80(3):431-442. doi: 10.1016/j.jhep.2023.10.040. Epub 2023 Nov 
      15.