Established and emerging therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a worldwide increasing incidence. The incidence of HCC is closely related to the epidemiology of the risk factors which are mainly represented by chronic viral hepatitis B and C. Obesity and type II diabetes, often associated with chronic nonalcoholic fatty liver disease, are emerging independent risk factors for HCC development. Although the risk factors for HCC are well characterized, the molecular mechanisms responsible for malignant transformation of hepatocytes are not well understood. HCC diagnosis and therapy follow defined algorithms according to the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases guidelines. Liver transplantation has been shown the best outcome for selected patients with early tumor stage but its application is limited by the shortage of liver grafts. After hepatic resection prognosis remains unsatisfactory due to a high incidence of tumor recurrence. Selective internal radiation therapy is emerging as promising loco-regional treatment for patients with advanced HCC having good performance status and liver reserve but not amenable to surgery. The recently introduced orally active multikinase inhibitor sorafenib has been established as palliative systemic therapy. Further improved understanding of molecular mechanisms underlying HCC development will facilitate the development of new targeted therapeutic strategies.