Natural history of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a slowly growing tumor, whose natural history is not completely known. Since the hepatocarcinogenetic process may evolve for years in a stepwise fashion from premalignant to overt HCC, detection of early, better treatable tumors is made possible by surveillance of patients at risk. A 6-month interval surveillance with ultrasound is considered cost-effective, generally leading to the identification of a single < 3 cm tumor in 50-70% of the patients at risk. For greater than 2 cm tumors, demonstration of arterial hypervascularization of the node by sonovue US, triphasic spiral CT or MRI is diagnostic for HCC. The diagnosis of a less than 2 cm in diameter tumor may be more difficult due to the risk of false negative diagnoses with contrast imaging technique (50% of the cases) caused by immature arterial vascularization of the small nodules. Prognosis largely depends on the evolutionary stage at which HCC is detected, i.e. a size and number of HCC nodes, vascular invasiveness and degree of liver impairment. The multinodular pattern of HCC, representing one third of all early cancers, heralds poor prognosis, especially for patients not fitting the Milan criteria for liver transplantation. The best prognosis is for a single, less than 5 cm node in compensated cirrhosis without vascular invasion, since this tumor is amenable to both liver transplantation and hepatic resection which may confer long-term survival. Better survivals of cirrhotic patients with a recently identified tumors reflect the application of accurate criteria for tumor staging and stringent criteria for curative treatments. However, ageing of the patients, deterioration of liver function during surveillance, occurrence of multinodular tumors and limited access to liver transplantation may hamper surveillance programs effectiveness.