Hepatocellular carcinoma: An Update

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC 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 the early detection of HCC in patients at risk, patient survival has not significantly improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and the limited therapeutic options. The therapeutic options fall into several categories: (i) surgical interventions including tumor resection and liver transplantation, (ii) percutaneous interventions including ethanol injection and radiofrequency thermal ablation, (iii) transarterial interventions including embolization, chemoembolization and selective internal radiotherapy, (iv) external radiation therapy and (v) systemic strategies with cytotoxic agents and molecularly targeted therapies as well as immunotherapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for actual therapeutic recommendations. While surgery, percutaneous and 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 HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care (BSC). In order to reduce the morbidity and mortality from HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including cytotoxic agents, molecular targeted and immunotherapies is most important. New analytical technologies, including gene expression profiling and proteomic analyses and others, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.