Gut 63:844-855 doi:10.1136/gutjnl-2013-306627
  • Recent advances in clinical practice

Hepatocellular carcinoma: clinical frontiers and perspectives

Editor's Choice
  1. Vincenzo Mazzaferro4
  1. 1Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
  2. 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
  3. 3Mayo Clinic, Mayo College of Medicine, Rochester, Minnesota, USA
  4. 4Gastrointestinal Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS (National Cancer Institute), Milan, Italy
  1. Correspondence to Dr Jordi Bruix, BCLC Group, Liver Unit, Hospital Clínic, C/Villarroel 170, Barcelona 08036, Spain; jbruix{at}
  • Received 17 December 2013
  • Revised 3 January 2014
  • Accepted 19 January 2014
  • Published Online First 14 February 2014


Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies.

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