Epidemiology, mutational landscape and staging of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and rates of diagnosis have been fluctuating worldwide. In Western countries, HCC is driven primarily by the hepatitis C virus (HCV), alcohol use and non-alcoholic fatty liver disease (NAFLD). Hence, it is not surprising that the increased incidence of both HCV and NAFLD has been associated with a corresponding rise in rates of HCC. The introduction of antiviral medications could potentially change the landscape of HCC by reducing rates of HCV-associated HCC. In Eastern countries and Africa, HCC is driven primarily by hepatitis B virus (HBV), HCV, and to a lesser extent, aflatoxin exposure. The introduction of hepatitis B vaccines is expected to dramatically reduce hepatitis B induced liver damage and HCC. These varying etiologies of HCC result in different mutational landscapes, patient presentations and responses to treatment. This has made establishing a universal staging system difficult and several competing systems are available. Other than Sorafenib, there has also been a paucity of treatment options until the last two years, with immunotherapy and new-targeted tyrosine kinase inhibitors as potential treatment options. Management of HCC offers unique challenges during treatment, as there is often competing illness from underlying liver dysfunction and malignancy itself, both of which affects survival and treatment choice. The new era of treatment may offer additional options in this challenging field. In this review, we describe the underlying etiologies and associated mutational landscape, which drives the treatment options in this complex disease.