Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function.

The number of effective systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC) is rapidly increasing, and the advent of immunotherapy has changed the treatment paradigm for these patients, leading to significantly improved survival outcomes. However, many patients with HCC will continue to receive tyrosine kinase inhibitors, partly because of contraindications to immune checkpoint inhibitors. Currently, the best sequential first- and second-line systemic treatment remains elusive. Maintenance of optimal liver function is crucial, it is likely to impinge on temporary or permanent treatment discontinuation, and should also be considered when defining the treatment sequence. Hepatic decompensation, which does not always coincide with disease progression, is part of this complex dynamically evolving system, and must be promptly recognized and adequately managed to allow the patient to continue in the therapeutic course. The purpose of this review is to highlight and summarize the evidence on the efficacy and safety of systemic agents, with a focus on the impact of underlying cirrhosis, and to suggest new clinical outcomes for randomized controlled trials for advanced HCC to better assess the net health benefit in this specific setting.

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Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Giuseppe Cabibbo has served as a consultant or on advisory boards for Bayer, Eisai, and Ipsen. Alessio Aghemo received grants from Abbvie, and served on board for advisory board for Gilead, abbvie, Gilead, Sobi, Intercept, MSD, Mylan, Shire. Quirino Lai: no conflict of interest exists.-        Mario Masarone: travel grants, invited speeches, advisory boards: gilead & abbvie. Travel grants: Alfasigma; advisory board: intercept. Sara Montagnese has received research funding from AlfaSigma S.p.a., Norgine Ltd., Merz Pharmaceuticals GmbH, Umecrine Cognition AB and Versantis AG.-        Francesca Romana Ponziani served as a consultant for consultant for Bayer, MSD, EISAI, Ipsen, Abbvie, Gilead, Alfasigma.