cancers Review Overview of Prognostic Systems for Hepatocellular Carcinoma and ITA.LI.CA External Validation of MESH and CNLC Classifications Alessandro Vitale 1 , Fabio Farinati 1 , Michele Finotti 1, *, Chiara Di Renzo 1 , Giuseppina Brancaccio 2 , Fabio Piscaglia 3,4 , Giuseppe Cabibbo 5 , Eugenio Caturelli 6 , Gabriele Missale 7 , Fabio Marra 8 , Rodolfo Sacco 9 , Edoardo G. Giannini 10 , Franco Trevisani 11, * , Umberto Cillo 1 , Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group 12,† and Italian Liver Cancer (ITA.LI.CA) Study Group 11,‡   Citation: Vitale, A.; Farinati, F.; Finotti, M.; Di Renzo, C.; Brancaccio, G.; Piscaglia, F.; Cabibbo, G.; Caturelli, E.; Missale, G.; Marra, F.; et al. Overview of Prognostic Systems for Hepatocellular Carcinoma and ITA.LI.CA External Validation of MESH and CNLC Classifications. Cancers 2021, 13, 1673. https://doi.org/ 10.3390/cancers13071673 Academic Editor: Alfred Sze-Lok Cheng Received: 28 February 2021 Accepted: 25 March 2021 Published: 2 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Departmentof Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; alessandro.vitale.10@gmail.com (A.V.); fabio.farinati@unipd.it (F.F.);germanclamp@outlook.com (C.D.R.); umberto.cillo@gmail.com (U.C.) 2 Infectious Diseases Unit, Department of Internal Medicine, Padua University Hospital, 35123 Padua, Italy; ggbrancaccio@gmail.com 3 Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; fabio.piscaglia@unibo.it 4 Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy 5 Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, 90127 Palermo, Italy; g.cab@libero.it 6 Gastroenterology Unit, Belcolle Hospital, 01100 Viterbo, Italy; e.caturelli@tiscalinet.it 7 Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, 43126 Parma, Italy; gabriele.missale@unipr.it 8 Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, 50139 Firenze, Italy; fabio.marra@unifi.it 9 Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, 71122 Foggia, Italy; saccorodolfo@hotmail.com 10 Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; egiannini@unige.it 11 Division of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 12 HCC Special Interest Group, Associazione Italiana per lo Studio del Fegato (AISF), 00199 Roma, Italy * Correspondence: mi6le@libero.it (M.F.); franco.trevisani@unibo.it (F.T.) † Membership of the AISF HCC Special Interest Group is provided in the Acknowledgments. ‡ Membership of the Italian Liver Cancer (ITA.LI.CA) study group is provided in the Acknowledgments. Simple Summary: This review proposes a comprehensive overview of the main prognostic systems for HCC classified as prognostic scores, staging systems, or combined systems. Prognostic systems for HCC are usually compared in terms of homogeneity, monotonicity of gradients, and discrimination ability. However, despite the great number of published studies comparing HCC prognostic systems, it is rather difficult to identify a system that could be universally accepted as the best prognostic scheme for all HCC patients encountered in clinical practice. In order to give a contribute in this topic, we conducted a study aimed at externally validate the MESH score and the CNLC classification using the ITA.LI.CA database. Abstract: Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic Cancers 2021, 13, 1673. https://doi.org/10.3390/cancers13071673 https://www.mdpi.com/journal/cancers