Introduction

Hepatocellular carcinoma (HCC) is the leading cause of death among cirrhotic patients and ranks third in cancer-related mortality worldwide (1). HCC usually develops as a consequence of chronic exposure to various environmental risk factors, including chronic hepatitis B and C viral infection, alcohol consumption, aflatoxin B1 intake from contaminated food, and other agents causing liver cirrhosis (2). Hepatitis B virus (HBV) vaccination has successfully decreased the incidence of HCC cases in Asia (3), but the increase in hepatitis C virus (HCV)-related liver disease has led to an increment of HCC in Western countries (4). Treatment considerations are often complicated by the co-existence of liver cirrhosis. Thus, an accurate assessment of tumor progression and liver dysfunction determines patient prognosis and drives treatment strategy, according to the widely accepted Barcelona-Clínic Liver Cancer (BCLC; 5,6) staging system. This therapeutic algorithm is endorsed by the American and European Association for the study of the liver in their clinical management guidelines (7,8).

Curative treatments have low applicability in the West because many patients are diagnosed at an advanced stage. Different studies show that less than 40% of HCC patients will be eligible for such therapies (e.g. resection, transplantation, or percutaneous ablation; 9). However, during the last 30 years, there have been major advancements in HCC management, in addition to significant milestones in the characterization of its molecular determinants (10). For example, the multi-kinase inhibitor sorafenib, represents the first systemic agent able to significantly improve overall survival in HCC patients with advanced tumors (11). This breakthrough has important implications for HCC research and the prospective design of clinical trials (6). New insights into the molecular pathogenesis will accelerate the deployment of individualized therapies for HCC.