Current management of advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for 6% of all cancers worldwide. In the United States, the incidence is expected to increase due to the increased rate of hepatitis C viral infection affecting that region. Other factors that will influence higher incidence rates for HCC include the persistent presence of alcoholic cirrhosis and the recently recognized correlation between non-alcoholic steatohepatitis (NASH) and HCC. In most cases, cirrhosis is an integral part of the morbidity and mortality associated with HCC, and must be accounted for in order to manage patients with HCC properly. Historically, medical oncologists used the Child-Pugh scoring system of cirrhosis. However, Child-Pugh only categorizes the cirrhosis and does not address factors intrinsic to the cancer itself, which is recognized as a major limitation of that system. The idea of incorporating cancer-related parameters was developed by several research groups. The Cancer of the Liver Italian Program (CLIP) score and the Chinese University Prognostic Index (CUPI) are among many others that were developed and are of great use for patients with hepatitis C- and hepatitis B-associated HCC, respectively. Many chemotherapeutic agents have been tested in HCC, with reported response rates between 10% and 15% and no demonstrated survival advantage. Over the past decade, several molecular targets involved in the etiology of HCC have been identified. Recently, sorafenib, an antiangiogenic and Raf kinase inhibitor, has shown a survival advantage. The innovative therapeutic outcomes associated with novel targeted therapies illustrates the need for biologic and pharmacokinetic end points to define their optimal doses and therapeutic effects.