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Nat Rev Dis Primers. 2016 Apr 14;2:16018. doi: 10.1038/nrdp.2016.18.

Hepatocellular carcinoma.

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Liver Cancer Program, Division of Liver Diseases and RM Transplant Institute, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, Madison Avenue 1425, 11F-70, Box 1123, New York, New York 10029, USA.
Liver Cancer Translational Research Laboratory, Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, IDIBAPS - Hospital Clinic, CIBERehd, University of Barcelona, Catalonia, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
INSERM, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Equipe Labellisée Ligue Contre le Cancer, Institut Universitaire d'Haematologie, Paris, France.
Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
Université Paris 13, Sorbonne Paris Cité, Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine, Bobigny, France.
Université Paris Diderot, Paris, France.
Lautenberg Center for Immunology and Cancer Research and Department of Pathology, Hebrew University Hadassah-Medical School, Jerusalem, Israel.
Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain.
Instituto de Investigación Sanitaria de Navarra (IDISNA) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Pamplona, Spain.
Department of Gastroenterology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Mayo Clinic, Mayo College of Medicine, Rochester, Minnesota, USA.


Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches.

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