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

  • Giuseppe Cabibbo
    Correspondence
    Corresponding author at: Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, Piazza delle Cliniche n 2, 90127, Italy.
    Affiliations
    Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
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  • Alessio Aghemo
    Affiliations
    Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

    Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Italy
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  • Quirino Lai
    Affiliations
    General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
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  • Mario Masarone
    Affiliations
    Internal medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology “Scuola Medica Salernitana” - University of Salerno, Baronissi (Salerno), Italy
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  • Sara Montagnese
    Affiliations
    Department of Medicine, University of Padova, Italy
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  • Francesca Romana Ponziani
    Affiliations
    Internal Medicine and Gastroenterology - Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

    Università Cattolica del Sacro Cuore, Rome, Italy
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  • on behalf of thethe Italian Association for the Study of the Liver (AISF)
Published:February 04, 2022DOI:https://doi.org/10.1016/j.dld.2022.01.122

      Abstract

      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.

      Abbreviations:

      HCC (Hepatocellular Carcinoma), OS (Overall Survival), TTP (Time to Progression), PFS (Progression Free Survival), TTD (Time to Decompensation), DFS (Decompensation Free Survival), TKIs (tyrosine kinase inhibitors), ICIs (immune checkpoint inhibitors), DAAs (direct acting antivirals), RCT (Randomized Controlled Trials), RECIST (response evaluation criteria in solid tumors), ORR (Objective Response Rate), DCR (Disease Control Rate)

      Keywords

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