Hepatocellular carcinoma: an update

Hepatocellular carcinoma is one of the most common malignant tumors worldwide. The major etiologies and risk factors for HCC development are well-defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for early hepatocellular carcinoma detection in patients at risk, patient survival has not yet significantly improved during the last three decades. This is in part due to the advanced stage of the disease at the time of diagnosis, and in part due to the limited therapeutic options. These fall into five main categories: 1) surgical interventions, including liver transplantation; 2) percutaneous interventions, including ethanol injection and radiofrequency thermal ablation; 3) transarterial interventions; 4) radiation therapy; and 5) drugs as well as gene and immune therapies. While surgery and percutaneous as well as transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis, more than 80% of patients present with multicentric hepatocellular carcinoma and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. Therefore, early diagnosis, the development of novel systemic therapies for advanced disease and hepatocellular carcinoma prevention are of paramount importance. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying hepatocellular carcinoma development and to identify novel diagnostic markers as well as therapeutic and preventive targets.