Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Journal Pre-proof Assessing the impact of COVID-19 on liver cancer management (CERO-19) Sergio Muñoz-Martínez, Victor Sapena, Alejandro Forner, Jean-Charles Nault, Gonzalo Sapisochin, Lorenza Rimassa, Bruno Sangro, Jordi Bruix, Marco Sanduzzi- Zamparelli, Wacław Hołówko, Mohamed El Kassas, Tudor Mocan, Mohamed Bouattour, Philippe Merle, Frederik J.H. Hoogwater, Saleh A. Alqahtani, Helen L. Reeves, David J. Pinato, Emmanouil Giorgakis, Tim Meyer, Gerda Elisabeth Villadsen, Henning Wege, Massimiliano Salati, Beatriz Mínguez, Giovan Giuseppe Di Costanzo, Christoph Roderburg, Frank Tacke, María Varela, Peter R. Galle, Mario Reis Alvares-da-Silva, Jörg Trojan, John Bridgewater, Giuseppe Cabibbo, Christian Toso, Anja Lachenmayer, Andrea Casadei-Gardini, Hidenori Toyoda, Tom Lüdde, Rosanna Villani, Ana María Matilla Peña, Cassia Regina Guedes Leal, Monica Ronzoni, Manuel Delgado, Christie Perelló, Sonia Pascual, José Luis Lledó, Josepmaria Argemi, Bristi Basu, Leonardo da Fonseca, Juan Acevedo, Alexander R. Siebenhüner, Chiara Braconi, Brandon M. Meyers, Alessandro Granito, Margarita Sala, Carlos Rodríguez Lope, Lorraine Blaise, Manuel Romero-Gómez, Federico Piñero, Dhanny Gomez, Vivianne Mello, Rogerio Camargo Pinheiro Alves, Alex França, Fernanda Branco, Giovanni Brandi, Gustavo Pereira, Susanna Coll, Maria Guarino, Carlos Benítez, Maria Margarita Anders, Juan C. Bandi, Mercedes Vergara, Mariona Calvo, Markus Peck-Radosavljevic, Ignacio García-Juárez, Vincenzo Cardinale, Mar Lozano, Martina Gambato, Stefano Okolicsanyi, Dalia Morales Arraez, Alessandra Elvevi, Alberto E. Muñoz, Alberto Lué, Massimo Iavarone, Maria Reig PII: S2589-5559(21)00036-7 DOI: https://doi.org/10.1016/j.jhepr.2021.100260 Reference: JHEPR 100260 To appear in: JHEP Reports Received Date: 21 November 2020 Revised Date: 8 February 2021 Accepted Date: 9 February 2021 Please cite this article as: Muñoz-Martínez S, Sapena V, Forner A, Nault JC, Sapisochin G, Rimassa L, Sangro B, Bruix J, Sanduzzi-Zamparelli M, Hołówko W, El Kassas M, Mocan T, Bouattour M, Merle P, Hoogwater FJH, Alqahtani SA, Reeves HL, Pinato DJ, Giorgakis E, Meyer T, Villadsen GE, Wege H, Salati M, Mínguez B, Di Costanzo GG, Roderburg C, Tacke F, Varela M, Galle PR, Alvares-da-Silva MR, Trojan J, Bridgewater J, Cabibbo G, Toso C, Lachenmayer A, Casadei-Gardini A, Toyoda H, Lüdde T, Villani R, Matilla Peña AM, Guedes Leal CR, Ronzoni M, Delgado M, Perelló C, Pascual S, Lledó JL, Argemi J, Basu B, da Fonseca L, Acevedo J, Siebenhüner AR, Braconi C, Meyers BM, Granito A, Sala M, Rodríguez Lope C, Blaise L, Romero-Gómez M, Piñero F, Gomez D, Mello V, Pinheiro Alves RC, França A, Branco F, Brandi G, Pereira G, Coll S, Guarino M, Benítez C, Anders MM, Bandi JC, Vergara M, Calvo M, Peck-Radosavljevic M, García-Juárez I, Cardinale V, Lozano M, Gambato M, Okolicsanyi S, Arraez DM, Elvevi A, Muñoz AE, Lué A, Iavarone M, Reig M, Assessing the impact of COVID-19 on liver cancer management (CERO-19), JHEP Reports (2021), doi: https://doi.org/10.1016/ j.jhepr.2021.100260. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2021 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). Jo ur na lP re -p ro of Assessing the impact of COVID-19 on liver cancer management (CERO-19) Sergio Muñoz-Martínez1, Victor Sapena1, Alejandro Forner1, Jean-Charles Nault2, Gonzalo Sapisochin3, Lorenza Rimassa4, Bruno Sangro5, Jordi Bruix1, Marco Sanduzzi-Zamparelli1, Wacław Hołówko6, Mohamed El Kassas7, Tudor Mocan8, Mohamed Bouattour9, Philippe Merle10, Frederik J.H. Hoogwater11, Saleh A. Alqahtani12, Helen L. Reeves13, David J. Pinato14, Emmanouil Giorgakis15, Tim Meyer16, Gerda Elisabeth Villadsen17, Henning Wege18, Massimiliano Salati19, Beatriz Mínguez20, Giovan Giuseppe Di Costanzo21, of Christoph Roderburg22, Frank Tacke22, María Varela23, Peter R. Galle24, Mario Reis Alvares- ro da-Silva25, Jörg Trojan26, John Bridgewater27, Giuseppe Cabibbo28, Christian Toso29, Anja -p Lachenmayer30, Andrea Casadei-Gardini31, Hidenori Toyoda32, Tom Lüdde33, Rosanna re Villani34, Ana María Matilla Peña35, Cassia Regina Guedes Leal36, Monica Ronzoni37, lP Manuel Delgado38, Christie Perelló39, Sonia Pascual40, José Luis Lledó41, Josepmaria Argemi42, Bristi Basu43, Leonardo da Fonseca44, Juan Acevedo45, Alexander R. na Siebenhüner46, Chiara Braconi47, Brandon M. Meyers48, Alessandro Granito49, Margarita ur Sala50, Carlos Rodríguez Lope51, Lorraine Blaise2, Manuel Romero-Gómez52, Federico Jo Piñero53, Dhanny Gomez54, Vivianne Mello55, Rogerio Camargo Pinheiro Alves56, Alex França57, Fernanda Branco58, Giovanni Brandi59, Gustavo Pereira60, Susanna Coll61, Maria Guarino62, Carlos Benítez63, Maria Margarita Anders64, Juan C. Bandi65, Mercedes Vergara66, Mariona Calvo67, Markus Peck-Radosavljevic68, Ignacio García-Juárez69, Vincenzo Cardinale70, Mar Lozano71, Martina Gambato72, Stefano Okolicsanyi73, Dalia Morales Arraez74, Alessandra Elvevi75, Alberto E. Muñoz76, Alberto Lué77, Massimo Iavarone78# and Maria Reig1#. Affiliations: 1 1. BCLC group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS. CIBERehd. University of Barcelona. Spain. 2. Service d’hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint- Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France. Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris Nord, Paris, France. Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F- 75006, Paris, France. 3. Abdominal Transplant & HPB Surgical Oncology, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Canada. 4. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center – IRCCS, Rozzano (Milan), Italy. Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Milan), Italy of 5. Unidad de Hepatología, Clínica Universidad de Navarra, IDISNA, CIBERehd, Pamplona, Spain. ro 6. Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. -p 7. Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt. re 8. 3rd Medical Department, "Octavian Fodor" Institute for Gastroenterology and Hepatology, Cluj-Napoca, Romania. lP 9. AP-HP, Hôpital Beaujon, Department of Digestive Oncology, Clichy, France. 10. Hepatology, Groupement Hospitalier Lyon Nord, Lyon, France. na 11. Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen, The Netherlands. 12. Liver Transplant, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi ur Arabia. 13. Liver Unit, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Jo 14. Department of Surgery and Cancer, Imperial College London, London, United Kingdom. 15. Division of Transplantation, Department of Surgery, UAMS Medical Center, Winthrop P. Rockefeller Cancer Institute, Little Rock, United States. 16. Oncology, Royal Free Hospital, London, UK. 17. Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 18. Department of Internal Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 19. PhD Program, Clinical and Experimental Medicine, University Hospital of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy. 20. Liver Unit, Hospital Universitari Vall d´Hebron, Liver Diseases Research Group, Vall d´Hebron Institut of Research (VHIR), Vall d´Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona, Barcelona, Spain. 21. Liver Unit, A Cardarelli Hospital, Naples, Italy. 2 22. Department of Hepatology and Gastroenterology, Charité- University medicine Berlin, Berlin, Germany. 23. Department of Gastroenterology and Hepatology. Hospital Universitario Central de Asturias. IUOPA. ISPA. Universidad de Oviedo. Oviedo, Spain. 24. I. Dept. of Internal Medicine, University Medical Center Mainz, Mainz, Deutschland. 25. GI/Liver Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 26. Medical Clinic 1, Goethe University Hospital, Frankfurt, Germany. 27. Oncology, University College of London, London, United Kingdom. 28. Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy. 29. Department of Surgery, Geneva University Hospitals, Geneva, Switzerland. of 30. Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland. ro 31. Medical Oncology, University of Modena and Reggio Emilia, Modena, Italy. 32. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. -p 33. Clinic for Gastroenterology, Hepatology and Infectious Disease, University Hospital Düsseldorf, Düsseldorf, Germany. re 34. Liver Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy. lP 35. Gastroenterology and Hepatology, H.G.U. Gregorio Marañon, CIBERehd, Madrid, Spain. na 36. Gastroenterology, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. 37. Medical Oncology Unit, IRCCS Ospedale San Raffaele, Milan, Italy. ur 38. Digestive Disease, University Hospital La Coruña, La Coruña, Spain. 39. Gastroenterology and Hepatology, University Hospital Puerta de Hierro, Jo Majadahonda, Spain. 40. Liver Unit, HGU Alicante. CIBERehd. Alicante, Spain. 41. Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Madrid, Spain. 42. Internal Medicine - Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain. 43. Department of Oncology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 44. Clinical Oncology, Sao Paulo Clinicas Liver Cancer gourp. Insitituto do Cancer do Estado de Sao Paulo. University of Sao Paulo, Brazil. 45. South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom. 46. Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland. 47. Medical Oncology, Beatson West of Scotland Cancer Centre /. University of Glasgow, Glasgow, UK. 3 48. Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Canada. 49. Division of Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna. Department of Medical and Surgical Sciences, University of Bologna, via Albertoni 15, Bologna, Italia. 50. Gastroenterology, Hepatology Unit, Hospital Doctor Josep Trueta, CIBERehd, Girona, Spain. 51. Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain. 52. SeLiver group. UGC de Enfermedades Digestivas, Instituto de Biomedicina de Sevilla- Hospital Virgen del Rocío-CIBERehd, Seville, Spain. 53. Liver Unit, Hospital Universitario Austral, Pilar, Argentina. of 54. HPB Surgery and Hepatology, Nottingham University Hospitals NHS Trust, Nottingham, UK. ro 55. Oncology, AMO, Salvador, Brazil. 56. Gastroenterology, Hospital do Servidor Publico Estadual de São Paulo, Sao Paulo, Brazil. -p 57. Medicine, Federal University of Sergipe, Aracaju, Brazil. re 58. Hepatology, Clinionco, Porto Alegre, Brazil. 59. Division of Oncology - Department of Experimental, Diagnostic and Specialty lP Medicine, S.Orsola-Malpighi Hospital, Bologna, Italy. 60. Gastroenterology and Hepatology Unit, Hospital Federal de Bonsucesso, Rio de na Janeiro, Brazil. 61. Hepatology section, Gastroenterology Department, Hospital del Mar. IMIM (Hospital ur del Mar Medical Research Institute). Barcelona, Spain. 62. Dpt of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy. Jo 63. Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile. 64. Sección hepatología, Hospital Aleman, Buenos Aires, Argentina. 65. Hepatology, Hospital Italiano, Buenos Aires, Argentina. 66. Unitat d’Hepatologia. Servei d’Aparell Digestiu. Parc Taulí Sabadell Hospital Universitari. Institut d’Investigació i Innovació I3PT. Universitat Autònoma de Barcelona. Sabadell. Barcelona. Departament de Medicina. Universitat Autònoma de Barcelona. Bellaterra. Spain. CIBERehd. Instituto Carlos III. Madrid. 67. Oncología Médica, Institut Català d'Oncologia, L'Hospitalet del Llobregat, Spain. 68. Innere Medizin & Gastroenterologie, Klinikum Klagenfurt am Wörthersee, Klagenfurt am Wörthersee, Austria. 69. Gastroenterology Department, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico. 70. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Italy. 71. Aparato Digestivo, Hospital Universitario Infanta Leonor, Madrid, Spain. 4 72. Department of Surgery, Oncology and Gastroenterology Padua University Hospital, Padua, Italy, Multivisceral Transplant Unit, Gastroenterology, Padua, Italy. 73. Department of Surgical Disciplines, Gastroenterology and Digestive Endoscopy, Umberto Parini Hospital, Aosta, Italy. 74. Gastroenterology and Hepatology, Hospital Universitario de Canarias, La Laguna, Spain. 75. Division Gastroenterology and Center for Autoimmune Liver Diseases San Gerardo Hospital University of Milano - Bicocca School of Medicine Monza, Italy. 76. Sección Hepatología, Hospital Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina. 77. Gastroenterology, Hepatology and Nutrition Unit, San Jorge General Hospital, Huesca, Spain. of 78. Foundation IRCCS Ca’ Granada Ospedale Maggiore Policlinico – Division of Gastroenterology and Hepatology – CRC “A.M. and A. Migliavacca” Center for ro Liver Disease, Milan, Italy. # Corresponding authors: -p re lP Massimo Iavarone: Foundation IRCCS Ca’ Granada Ospedale Maggiore Policlinico – Division of Gastroenterology and Hepatology – CRC “A.M. and A. Migliavacca” na Center for Liver Disease, Milan, Italy. Maria Reig: BCLC group, Liver Unit, IMDiM, CIBERehd, IDIBAPS, Hospital Clínic, ur c/ Villarroel, 170, Escala 11, 4a planta, 08036 Barcelona. Spain. Tel.: +34 932279803, Jo fax: +34 932275792. E-mail address: mreig1@clinic.cat ORIGINAL STUDY Keywords: COVID-19, Hepatocellular carcinoma, cholangiocarcinoma, liver cancer, management, clinical trials, nurses Data availability statement: Research data are not available for sharing given their confidential nature. 5 Disclosures: SM.-M. Speaker fees from Bayer and travel funding from Bayer and Eisai. V.S. Travel grants from Bayer. A.F. Lecture fees from Bayer, Gilead and MSD; consultancy fees from Bayer, AstraZeneca, Roche and Guerbert. J-C.N. Received research grant from Bayer for Inserm UMR1138. L.R. Reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO of BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Roche. ro B.S. reports consultancy fees from Adaptimmune, AstraZeneca, Bayer, BMS, BTG, Eli Lilly, -p Ipsen, Novartis, Merck, Roche, Sirtex Medical, Terumo; and research grants from BMS and Sirtex Medical. re J. Bruix. Consultancy: AbbVie, ArQule, Astra, Basilea, Bayer, BMS, Daiichi Sankyo, GlaxoSmithKline, Gilead, Kowa, Lilly, Medimune, Novartis, Onxeo, Polaris, Quirem, Roche, lP Sanofi-Aventis, Sirtex, Terumo/Grants: Bayer and Ipsen. na M.S.Z. received speaker fees and travel grants from Bayer and BTG, MSD. M.B. Consultant and advisory Board for: Bayer Pharma, Ipsen, BMS, Eisai, Roche, ur AstraZeneca, Sirtex Medical. Jo D.J.P. Received lecture fees from ViiV Healthcare and Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and AstraZeneca; received research funding (to institution) from MSD and BMS. T.M. Consultancy: Eisai, Roche, BTG, Ipsen, Bayer, Adaptimmune. Research funding: Bayer, BTG. H.W. Served as speaker for Bayer, Eisai, and Ipsen, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche, and Ipsen. B.M. Consultancy: Bayer-Shering Pharma /Speaker fees: Eisai, MSDG. C. Consultancy fees from Bayer, Ipsen. P. R. G. Bayer, BMS, MSD, AstraZeneca, Adaptimmune, Sirtex, Lilly Ipsen, Roche, Eisai. M.R.A.S. Has received Research grants, advisory board or speaker for AbbVie, Bayer, Biolab, Intercept, Ipsen, Gilead, MSD, Novartis, and Roche. 6 J.T. Has received research grants from Roche and Ipsen. He has received speaker and consulting honoraria from AstraZeneca, Amgen, Bayer Healthcare, Bristol Myers-Squibb, Eisai, Ipsen, Merck Serono, Merck Sharp & Dome, Lilly Imclone, and Roche. J. Bridgewater Consultancy Bayer, BMS, Incyte, Taiho, Roche, MSD and Merck Serono. Research funding from Incyte. G.C. Consultancy fees from Bayer, Ipsen. A.L. Consultancy CAScination, Advisory Board Neuwave and Histosonics. H.T. Speaker fees from AbbVie, Gilead, MSD, and Bayer. R.V. Research grant from Abbvie. A.M.M.P. Speaker honorarium from Bayer, BMS, Boston Scientific and EISAI. Consulting of honorarium from Bayer, AstraZeneca and EISAI. Advisory honorarium from Bayer, AstraZeneca and EISAI. Grants from Bayer and Boston Scientific. ro M.D. Has received consulting and training fees from Bayer and Eisai. -p B.B. reports Consultancy for GenMab (paid to Institution); Advisory Boards for Roche (paid re to Institution), Eisai Europe Limited (paid to Institution), research grant from Celgene Ltd (paid to Institution), Speakers Bureau for Eisai Europe Limited (paid to Institution), Travel and registration for Congress from Bayer. lP L.d.F. Lectures fees from BMS, Roche and Bayer. na B.M.M. Advisory/Speaker: Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Merck, Roche, Sanoffi Genzyme, Taiho. Expert Testimony: Eisai, Roche. Travel: Eisai, Merck. Research: Sillajen (Individual); AstraZeneca, H3/Eisai, Galera, GSK, Exelixis (Institution). ur M.S. Travel/ accommodation/meeting expenses: Bayer. Eisai. Speaker fees: Bayer. Jo C.R.L. Travel grants from Bayer. M.R-G. Reports grants from Intercept, grants from Gilead-Sciences, personal fees from Shionogi, personal fees from Alfa-Wasserman, personal fees from Prosciento, personal fees from Kaleido, personal fees from Novonrdisk, personal fees from MSD, personal fees from BMS, personal fees from Allergan, personal fees from Boehriger-Ingelheim, personal fees from Zydus, personal fees from Intercept Pharma, personal fees from Gilead-Sciences, outside the submitted work F.P. Disclosures: Received speaker honoraria from Bayer, Roche, LKM-Biotoscana, RAFFO. Research Grants from INC Argentinean National Institute of Cancer, Roche. V.M. Lectures sponsored by Bayer. G.B. Advisory board Eli-Lilly and Incyte. M.Vergara Travel grants from Bayer, Gilead, MSD and Abbvie. Lectures sponsored by Gilead, Abbvie, Intercept and MSD. 7 M.L. Lectures and educational presentations: Abbvie. Travel/accommodations, meeting expenses covered by Bayer, Gilead, Abbvie. M.I. Received speaker honoraria from Bayer, Gilead Sciences, BMS, Janssen, Ipsen, MSD, BTG-Boston Scientific, AbbVie, EISAI and was consultant for BTG-Boston Scientific, Bayer and Guerbet. M.R. Consultancy: Bayer-Shering Pharma, BMS, Roche, Ipsen, AstraZeneca, Lilly, BTG/Paid conferences: Bayer-Shering Pharma, BMS, Gilead, Lilly/Research Grants: Bayer- Shering Pharma, Ipsen. Acknowledgements: of SM-M. received the grant support “Beca para Perfeccionamiento en Gastroenterología en el ro Extranjero” from Asociación Mexicana de Gastroenterología, A.C. -p A.F. received grant support from Instituto de Salud Carlos III (PI13/01229 and PI18/00542). re J.Bruix. received grant support from Instituto de Salud Carlos III (PI18/00768), AECC lP (PI044031), and WCR (AICR) 16-0026. M.S.Z. was supported by “Ajuts per a la iniciació a la recerca 2019 from Societat Catalana de na Digestologia (SCD)” and received grant support from Instituto de Salud Carlos III ur (FI19/00222). Jo H.L.R. is supported by funding from Cancer Research UK (CR UK) centre grant C9380/A18084; CR UK programme grant C18342/A23390 and CR UK Accelerator award HUNTER C9380/A26813. D.J.P. is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT) and infrastructural support by the Cancer Research UK Imperial Centre, the Imperial College Experimental Cancer Medicine Centre (ECMC) and the NIHR Imperial Biomedical Research Centre. B.M. received grant support from Instituto de Salud Carlos III (PI18/00961). 8 J. Bridgewater is in part funded by the UCLH/UCL Biomedical Reasearch Centre. M.S. received funding from CIBERehd (CB06/04/0033) and AGAUR (2017-SGR-490). M.R. received grant support from Instituto de Salud Carlos III (PI15/00145 and PI18/0358). Some of the authors of this article are members of the European Reference Network (ERN) RARE-LIVER. Some of the authors of this article are members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and participate in the initiative COST Action of EURO-CHOLANGIO-NET granted by the COST Association (CA18122) and European ro Commission Horizon 2020 program (ESCALON project #825510). -p re Abbreviation list lP LC: Liver Cancer CERO-19: Liver Cancer Outcome in the COVID-19-pandemic Project na ENS-CCA: European Network for the Study of Cholangiocarcinoma ur BCLC: Barcelona Clinic Liver Cancer Jo IQR: Interquartile range Abstract: 266 words Electronic word count (including abstract): 3,858 words Number of figures and tables: 3 figures and 3 tables Supplementary material: Here we will include the survey, 3 Tables and 2 Figures 9 Authors contributions: - MR and MI conceived and organized the study, planned the data management, organized data collection for the steering center, wrote the manuscript and figures, and gave their final approval of the manuscript. - MR, MI, AF, JCN, GZ, LR, BS and JB designed, reviewed and tested the survey. - SM-M, MR, MI, AF, JCN, GZ, LR, BS, HR and JB significantly contributed to the writing of the manuscript and gave the final approval before submission. of - VS planned and realized the statistical analyses. ro - All the Authors revised and edited the manuscript and gave their final approval before submission. -p re lP Financial support statement: no founding for this study na ur Jo 10 Abstract: BACKGROUND The coronavirus 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). This project has evaluated if the schedule of LC screening or procedures has been interrupted /delayed because of the COVID-19 pandemic. of MATERIAL AND METHODS ro An international survey evaluated the impact of COVID-19 pandemic on clinical practice and -p clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international re and observational project. The focus was on patients with hepatocellular carcinoma or lP intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. na ur RESULTS Jo Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia and Africa (73.7%, 17.1%, 5.3%, 2.6% and 1.3% per continent, respectively). Eighty-seven per cent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening program, 50% cancelled curative and/or palliative treatments for LC, and 44.0% cancelled the liver transplantation program. Forty-five out 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service prior to COVID-19 pandemic (n=19/37). 11 CONCLUSION The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with LC. Modifications in screening, diagnostic and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision making. of ro -p re lP na ur Jo 12 INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic has impacted all levels of society. In the absence of an available vaccine or therapy, healthcare authorities have mostly focused their efforts on reducing viral transmission in order to reduce the rate of COVID-19 pandemic related deaths. While recent studies have described the mortality in cancer patients diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as reaching 28.9% to of 33.6%, a relatively modest 4.4% to 5.5% has been reported patients cohorts including ro hepatobiliary cancers[1,2]. In the case of hepatocellular carcinoma (HCC) and some -p intrahepatic cholangiocarcinoma (iCCA), almost all patients also have underlying cirrhosis, re Marjot et al. reported that baseline liver disease stage and alcohol-related liver disease were lP independent risk factors for death from SARS-CoV-2 infection, increasing the risk of hepatic decompensation[3,4]. Even in the absence of these significant complications in liver cancer na (LC) patients infected with SARS-CoV-2, treatments have been suspended or delayed, in line ur with national or institutional policies. As an example, Amaddeo et al. have described how LC Jo care changed in the metropolitan area of Paris alongside with the evolution of the COVID-19 pandemic[5]. In addition to those infected by SARS-CoV-2, non-infected patients with LC may have also been affected by the COVID-19 pandemic related modifications in clinical practice and the priorities established for population health care. For future decision making, it is relevant to evaluate the consequences of interrupting or delaying the schedule of LC screening programs or treatments, as established before the COVID-19 pandemic, on LC prognosis. This is a multicentre, international and observational project, the Liver Cancer Outcome in the COVID-19-pandemic (CERO-19) project, focused on patients with HCC or iCCA, 13 managed during the COVID-19 pandemic. We describe here the results of the first part of the project, which was a survey to evaluate the impact of COVID-19 pandemic on international clinical practice and research. MATERIAL AND METHODS Centres around the world were invited to participate. The project was promoted through the ENS-CCA network, organizers’ personal Twitter account and the Barcelona Clinic Liver of Cancer (BCLC) account for a period of 4 weeks before starting the survey. The organizers of ro the project (MI, AF and MR) elaborated the survey and 5 independent LC experts -p reviewed/tested it and sent their suggestions (JCN, GZ, LR, BS, JB). The survey had re mandatory sections focused on Clinical Practice (related and non-related to COVID-19) and lP an optional section focused on Clinical Research. Survey and protocol details are summarized in the Supplementary material. na ur STATISTICAL ANALYSIS Jo The answers to the survey were expressed as absolute frequencies and percentages (%). The survey was developed and performed using the SurveyMonkey® platform. Raw data and results were directly extracted from the platform. SAS software® (v9.4) was used when more accurate approaches were required and to generate the figures. RESULTS The Liver Cancer centres taking part in the survey The survey was open from May 2020 to June 2020. Ninety-one centres were contacted or expressed interest to be involved and 81 survey responses were received (89% response). Five 14 were excluded: 4 due to duplication and 1 because their data was incorporated with that from another centre. The final analysis was based on information from 76 centres, including centres in Europe, South America, North America, Asia and Africa (73.7%, 17.1%, 5.3%, 2.6% and 1.3% respectively); Table 1. In combination, these centres cared in the pre-pandemic period for a total of 9,602 new LC patients per year, with a median [IQR] of 80 new visits/year [46.5 – 150], with the majority (77%) registered in Europe. In 2019, these centres, carried out 39,739 of and 6,347 follow-up visits for HCC and iCCA, respectively (Supplementary Tables S1 and ro S2). The profiles of centres included in the survey were heterogeneous: 76.3% of them -p included nurses in their team and 47.4% had phone call visits as part of their clinical practice re before COVID-19 pandemic (Supplementary Table S2). lP Liver Cancer Management modification during the first wave of the COVID-19 pandemic na Eighty-seven percent of the centres (n=66) modified their clinical practice during the COVID- ur 19 pandemic, with almost half (48%) decreasing the number of physicians devoted to Jo managing LC patients. Figure 1 describes the main areas where the clinical practice was modified: 80.9% modified the screening program, 73.5% changed the imaging follow-up in LC patients after treatment, 63.2% rescheduled surgical treatments and 52.9% locoregional therapies. Supplementary Figures 1 and 2 describe the percentage of areas in which clinical practices were modified according to the continent. Testing for SARS-CoV-2 infection before an outpatient visit for LC management was performed in 21.1% of centres (n = 16/76), increasing to testing in 76.3% (n = 58/76) before any pre-planned patient admission for LC treatment. Table 2 reports the criteria used for requesting a SARS-CoV-2 infection test in the different centres. 15 Ten centres reported no modification of their clinical practice due to COVID-19 pandemic. Of note, despite these centres continued offering their full range of LC care, 3/10 of these centres reported that patients were reluctant to come to the hospital due to concerns about the possibility of SARS-CoV-2 infection. Diagnostic strategy and staging procedures during the first wave of the COVID-19 pandemic Based on the 76 centres, 40.8% modified their diagnostic procedure requests and timing of (biopsy and imaging technique) during COVID-19 pandemic. 39.5% modified the Magnetic ro Resonance/Computed Tomography scan strategy for LC staging or treatment response -p evaluation. Figure 2 describes the criteria used to adhere the pre-defined schedule of re diagnostic and staging procedures. The most frequent criteria were the suspected tumour stage lP (75% and 63.6% for diagnosis and staging, respectively) and the degree of cancer suspicion (68.8 and 48.5%, respectively). na In 28% of centres, at least one asymptomatic SARS-CoV-2 infected patient was incidentally ur diagnosed due to radiology test done for the oncology indication. Jo Treatments options during the first wave of the COVID-19 pandemic Despite the modifications made during the COVID-19 pandemic, 96% of the centres maintained their ability to perform LC treatments. From 50 centres with liver transplantation (LT) program prior to COVID-19 pandemic, 28 (56.0%) (n = 28/50) of the centres did not modify the LT activity, while 60.8% of centres (n = 45/76) were able to perform surgical resections, 68.9% (n = 51/76) percutaneous treatments and 81.1% (n = 60/76) locoregional treatments. The option to initiate systemic treatment was maintained in 93.2% of the centres. 16 Figure 3 describes the criteria adopted to maintain an unaltered therapy schedule. The survey was not designed to evaluate on individual basis these criteria adopted by each centre. In 50% of the centres (n=38/76) curative and/or palliative treatments for LC were cancelled at least in one patient for each centre due to SARS-CoV-2 infection. Phone call visits, face-to-face visits, and the role of nurses during the first wave of COVID-19 pandemic of Based on 76 centres, phone call visit service was part of routine clinical practice before ro COVID-19 pandemic in 37 centres. It was modified in 19 of these centres (51.4%): an -p increase of the number of calls (more days and/or more hours/day) was the most frequent re modification in 84% of the centres, whereas 7 centres (17.9%) introduced phone call visits as lP a new practice during COVID-19 pandemic. Fifty centres included the type of visit (first vs. follow-up visit) and 53 centres the disease na status (stable disease vs. progressive disease) in their criteria guiding decisions on whether to ur convert a face-to-face visit into a phone call visit (68.9% and 71.6%, respectively). The age of Jo the patient and the patient address/distance to the hospital were adopted as criteria for phone call visits in 20 and 24 centres, respectively. Focused on the 58 centres which had nurses integrated into the LC team, the liver-oncology nurses made decisions regarding face-to-face versus phone call visits in 30.1% of the centres and organizing the visits in 70.3%. The nurses undertook the phone call visits in 62.5%, to answer questions about treatment or follow-up events. 17 Treatments in clinical trials in Liver Cancer patients during the first wave of the COVID-19 pandemic Of the 69 (90.8%) centres which answered this part of the survey, 45 (65.2%) of them had modified their management of clinical trials activity. Human resources, feasibilities, and sponsor`s recommendation were the main reasons for these modifications. Despite the modifications in management of clinical trials activities, 58.1% of the centres were able to recruit new patients during COVID-19 pandemic, but only 9.7% of centres of declared that the recruitment rate was similar to that before the pre-COVID-19 pandemic. In ro 46.2% of centres virtual visits by video or phone calls were done, and 29.9% of centres were -p forced to postpone visits (not transformed into virtual). Table 3 describes the most frequent re criteria for delaying treatments in clinical trials visits. lP DISCUSSION na To ameliorate COVID-19 pandemic impact on LC, several organizations advised multiple ur recommendations based on expert opinion data at the beginning of the first wave[6–9]. The Jo results of this survey highlight the potential clinical significance of the implemented modifications, predicting a likely major impact of COVID-19 pandemic on outcomes, given the magnitude of the disruption in patient care - from screening to diagnosis, staging and treatment-. According to the present results, all areas of clinical practice were modified during the COVID-19 pandemic first wave. The major changes related to the suspension of screening programs and surgical treatments (mainly liver transplantation), the decrease of face-to-face visits and the growing role of liver oncology-nurses as key members in the transformation of the digital management of LC in the context of the COVID-19 pandemic. 18 Notably, the approach maintained in almost all centres (93.2%) was systemic treatment LC patients. This may have been associated with the stage of the disease, stage being one of the priority criteria identified at the time of maintaining the planned schedule. The fact that the most widely used systemic therapies were oral tyrosine kinase inhibitors, which can be self- administered by the patient at home rather than requiring a visit to the hospital, is also likely to have played a role. Unfortunately, the disruption in screening programmes due to this health care crisis raises the of possible consequence of a shift towards a more advanced stage at diagnosis. Additionally, ro delays of interventional procedures such as transplant, resection or ablation may impact on -p tumour progression, dissemination and ultimately prognosis. Previous studies[10,11] re indicated that progression associated with poorer outcomes occurred as a consequence of lP waiting or delaying interventions beyond two months. Hanna et al. described a significant association between cancer treatment delay and increased mortality for 13 out of 17 na indications analyzed, although LC was not one of those analyzed[12]. Rich et al. have ur recently shown that the rate of liver tumour growth at early stages is very heterogeneous [13]. Jo This may be something that could be further evaluated in the context of screening ultrasound delays due to COVID-19 pandemic. Obviously, tumour stage at diagnosis will be one of the most relevant, as tumour growth is assumed to be faster along its evolution [14–16]. We should also keep in mind that the detection of changes in outcome or tumour progression during the delayed interventions may translate into a marginal impairment without clinically relevant consequences. It must also be noted in advance that any suggestion we raise in the future will not have the background that would be provided by a randomized controlled trial comparing conventional timing vs. delayed intervention. Despite this limitation, our future data will be instrumental in the identification of those areas where the changes induced by the 19 pandemic have been beneficial or detrimental. If the outcome at any step of the health care pathway is clearly worse, we would have an estimation of the deleterious consequences of COVID-19 pandemic beyond the infection itself. This may inform us on the most appropriate measures to be adopted in the future; either while this pandemic persists or repeats, as is happening with the current second wave, or should another public health crisis emerge in the future. The move from face-to-face visits to phone call visits encouraged during the pandemic may of improve patient care going forward, being potentially acceptable and preferable in some ro patients. The pandemic also reinforced the role of nurses [17,18], who were already part of -p LC teams in 76.3% of the centres, with their activity and responsibility appearing to have re increased. In some groups, where nurses were not previously part of the team, the COVID-19 lP crisis has promoted investment in their growing roles, in education and counselling of patients and their families. na The benefits and challenges related to the use of remote visits by nurses and physicians for ur cancer patients will be seen in the next months/years [17–19]. Not all patients and families Jo will be successfully served by remote visits and our data already reveal that there are several characteristics that may favour face-to-face or phone call visits. The age of the patient (which is a factor associated with severity in SARS-CoV-2 infected patients in cancers different to LC) [2] as well as the patient address and distance to the hospital (which could be associated with increased risk of exposure on their way to and from the hospital) were the less frequent factors considered to switch from face-to-face visit to a phone call visit in clinical practice. However, in patients included in treatments in clinical trials we observed that younger age of the patients and lack of comorbidities were criteria to favour phone call visits. This difference could be mainly related to the type of information to be given during a conventional clinical 20 practice visit related to diagnosis or/and tumour progression or the type of visit in the setting of treatments in clinical trials with experimental agents at risk of adverse events (first or follow-up visit). Indeed, since recruitment into treatments in clinical trials had been impacted (only 9.7% of centres maintained the same recruitment rate they had before the pandemic), almost all the visits within treatments in clinical trials have been devoted to follow-up assessments rather than new patient recruitment. As previous studies had shown [20,21], maintaining treatments in clinical trials activities requires a great effort and reorganization of of the LC team, to define a protocol to continue with these activities while protecting patients ro from contracting SARS-CoV-2 infection. -p The results of this survey describe the major changes that occurred in LC management in 76 re high volume centres around the world. However, 73.7% of centres that answered the survey lP were from Europe. In addition, the Italian and Spanish centres represented 55.4% of the European centres. Thus, the results of the survey could be overestimated by these 2 countries na which were severely affected by the first wave. Supplementary Table S3 describes the details ur of Europe without Italy and Spain and the data only from Italy and Spain, respectively. Jo In summary, despite of the fact that the survey was not focus on individual-patient information, the result of the survey reflects the consequence of the first wave of the COVID- 19 pandemic. These modifications in LC management may have significantly impacted the outcome of patients and public Health policy. The results of this survey may induce to predict that the profile of patients diagnosed after the first wave could be more advanced that we have usually have in the pre-pandemic era and will help us to identify confounding factors at the time of analysing the next phase the CERO-19 project. Future analyses will provide invaluable information around the clinical effectiveness of the strategies that have been implemented during this devastating health crisis. 21 REFERENCES [1] Pinato DJ, Zambelli A, Aguilar-Company J, Bower M, Sng CCT, Salazar R, et al. Clinical Portrait of the SARS-CoV-2 Epidemic in European Patients with Cancer. Cancer Discov 2020;10:1465–74. https://doi.org/10.1158/2159-8290.cd-20-0773. [2] Pinato DJ, Lee AJX, Biello F, Seguí E, Aguilar-Company J, Carbó A, et al. Presenting features and early mortality from SARS-CoV-2 infection in cancer patients during the initial stage of the COVID-19 pandemic in Europe. Cancers (Basel) 2020;12:1–13. https://doi.org/10.3390/cancers12071841. of [3] Marjot T, Moon AM, Cook JA, Abd-Elsalam S, Aloman C, Armstrong MJ, et al. Outcomes ro following SARS-CoV-2 infection in patients with chronic liver disease: an international -p registry study. J Hepatol 2020. https://doi.org/10.1016/j.jhep.2020.09.024. re [4] Iavarone M, D’Ambrosio R, Soria A, Triolo M, Pugliese N, Del Poggio P, et al. High rates of lP 30-day mortality in patients with cirrhosis and COVID-19. J Hepatol 2020;73:1063–71. https://doi.org/10.1016/j.jhep.2020.06.001. na [5] Amaddeo G, Brustia R, Allaire M, Lequoy M, Hollande C, Regnault H, et al. Journal Pre-proof ur Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area. JHEP Reports 2020:100199. https://doi.org/10.1016/j.jhepr.2020.100199. Jo [6] Meyer T, Chan S, Park J-W. ILCA Guidance for Management of HCC during COVID-19 Pandemic 8 th April 2020. n.d. [7] Boettler T, Marjot T, Newsome PN, Mondelli MU, Maticic M, Cordero E, et al. Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic. 2020. https://doi.org/10.1016/j.jhepr.2020.100169. [8] Mehta N, Parikh N, Kelley RK, Hameed B, Singal AG. Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic. Clin Gastroenterol Hepatol 2020. https://doi.org/10.1016/j.cgh.2020.06.072. [9] Kudo M, Kurosaki M, Ikeda M, Aikata H, Hiraoka A, Torimura T, et al. Treatment of hepatocellular carcinoma during the COVID 19 outbreak: The Working Group report of 22 JAMTT HCC. Hepatol Res 2020;50:1004–14. https://doi.org/10.1111/hepr.13541. [10] Cucchetti A, Trevisani F, Pecorelli A, Erroi V, Farinati F, Ciccarese F, et al. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma. J Hepatol 2014;61:333–41. https://doi.org/10.1016/j.jhep.2014.03.037. [11] Chen WT, Fernandes ML, Lin CC, Lin SM. Delay in treatment of early-stage hepatocellular carcinoma using radiofrequency ablation may impact survival of cirrhotic patients in a surveillance program. J Surg Oncol 2011;103:133–9. https://doi.org/10.1002/jso.21797. of [12] Hanna TP, King WD, Thibodeau S, Jalink M, Paulin GA, Harvey-Jones E, et al. Mortality due ro to cancer treatment delay: systematic review and meta-analysis. BMJ 2020;371:m4087. https://doi.org/10.1136/bmj.m4087. -p re [13] Rich NE, John B V., Parikh ND, Rowe I, Mehta N, Khatri G, et al. Hepatocellular carcinoma lP demonstrates heterogeneous growth patterns in a multi center cohort of patients with cirrhosis. Hepatology 2020:hep.31159. https://doi.org/10.1002/hep.31159. na [14] Cheng SJ, Freeman RB, Wong JB. Predicting the probability of progression-free survival in ur patients with small hepatocellular carcinoma. Liver Transplant 2002;8:323–8. https://doi.org/10.1053/jlts.2002.31749. Jo [15] Mehrara E, Forssell-Aronsson E. Analysis of inter-patient variations in tumour growth rate. Theor Biol Med Model 2014;11. https://doi.org/10.1186/1742-4682-11-21. [16] Kay K, Dolcy K, Bies R, Shah DK. Estimation of Solid Tumor Doubling Times from Progression-Free Survival Plots Using a Novel Statistical Approach. AAPS J 2019;21. https://doi.org/10.1208/s12248-019-0302-5. [17] Nalley C. Navigating the COVID-19 Pandemic as an Oncology Nurse. Oncol Times 2020;42:11. https://doi.org/10.1097/01.cot.0000661864.55789.d7. [18] Paterson C, Cert LTA P, Gobel B, Ò A, Gosselin T, Haylock PJ, et al. Oncology Nursing During a Pandemic: Critical Reflections in the Context of COVID-19 2020. https://doi.org/10.1016/j.soncn.2020.151028. 23 [19] Debes JD. Virtual empathy and liver cancer. Liver Int 2020;40:2571–2571. https://doi.org/10.1111/liv.14576. [20] D’Alessio A, Personeni N, Pressiani T, Bozzarelli S, Smiroldo V, Simonelli M, et al. COVID 19 and liver cancer clinical trials: Not everything is lost. Liver Int 2020;40:1541–4. https://doi.org/10.1111/liv.14532. [21] Waterhouse DM, Harvey RD, Hurley P, Levit LA, Kim ES, Klepin HD, et al. Early Impact of COVID-19 on the Conduct of Oncology Clinical Trials and Long-Term Opportunities for Transformation: Findings From an American Society of Clinical Oncology Survey. JCO Oncol of Pract 2020;16:417–21. https://doi.org/10.1200/op.20.00275. ro [22] Akl EA, Blazic I, Yaacoub S, Frija G, Chou R, Appiah JA, et al. Use of Chest Imaging in the -p Diagnosis and Management of COVID-19: A WHO Rapid Advice Guide. Radiology re 2020:203173. https://doi.org/10.1148/radiol.2020203173. lP Tables na Table 1. Distribution of the percentage of centres by continent included in the analysis ur Centres Continent % Jo Europe 73.7 South America 17.1 North America 5.3 Asia 2.6 Africa 1.3 24 Table 2. Description of the criteria used for testing SARS-CoV-2 infection in Clinical Practice reported by the different centres Before any pre-planned Before doing an Criteria for testing patient admission for outpatient visit for liver SARS-CoV-2 infection liver cancer treatment cancer treatment Number of centres which answer 58/76 centres 16/76 centres this part of the survey (n) SARS-CoV-2 infection clinical 35 (57.4%) 13 (81.3%) suspicion Pulmonary infiltrates suggestive of of COVID-19 by imaging done 25 (41%) 10 (62.5%) for cancer work-up in otherwise ro asymptomatic patient COVID-19 screening before 47 (77.1%) 9 (56.3%) hospital admission -p COVID-19 screening before 22 (36.1%) 7 (43.8%) treatment indication re Others 9 (14.8%) * 1 (6.3%) * * COVID-19 before invasive procedures. lP Table 3. Description of the criteria used for delaying visits in the clinical trials setting na reported by the different centres ur Centres Criteria n (%) Jo Number of centres which answer this part of 69 the survey (n) Number of centres which answer ‘yes’ this 20 (29.9%) part of the survey (n) Age 9 (35.5%) Comorbidities 11 (45.8%) Tumour stage 6 (25%) Clinical Trial phase 6 (25%) Treatment line (first therapy vs treatment of 8 (33.3%) recurrence / progression) Patient address and distance from hospital 10 (41.7%) 25 Figures Legends Figure 1. Areas in which pre-pandemic clinical practices were modified expressed as percentages. Grey bars represent the centres´ percentage that had to modify the clinical practice in the main areas mentioned in the figure´s left part. Figure 2. Criteria used to maintain pre-defined schedules of diagnostic and staging procedures. Grey bars represent the percentage of centres that used each of the criteria mentioned in the of figure´s left part to maintain pre-defined schedules of diagnostic and staging procedures. ro Figure 3. Criteria used to maintain the therapy schedule unaltered. -p Grey bars represent the percentage of centres that used each of the criteria mentioned in the re figure´s left part to maintain the therapy schedule unaltered. lP na ur Jo 26 Jo ur na lP re -p ro of Jo ur na lP re -p ro of Jo ur na lP re -p ro of Highlights. • The COVID-19 pandemic had a worldwide impact in liver cancer management. • The screening program were modified or cancelled in 80.9% of the centres. • All but systemic treatments were cancelled or delayed in almost all centres. • Phone call visits were the tool for patients` follow-up during the first wave. • The role of the nurses was key to maintain clinical practice and clinical trials of ro -p re lP na ur Jo