Viral hepatitis B and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world, some 630,000 new cases being diagnosed each year. 82% of cases are related to viral hepatitis, 55% to hepatitis B virus (HBV), 89% of those in regions where HBV is endemic. There is a striking parallel between the geographical distribution of the rates of chronic HBV infection and that of HCC. In the majority of HCC cases (70-90%) there is underlying liver cirrhosis. However, because HBV is an oncogenic virus, it can cause HCC in the absence of cirrhosis. The annual risk of HBV-induced HCC varies according to the presence or absence of concomitant cirrhosis. In HBV carriers without cirrhosis, the risk is 0.02-03% in Caucasians and 0.4-0.6% per year in Asians. In those with cirrhosis, the risk is 2.2% and 3.7% respectively in Caucasians and Asians. HBV likely causes HCC via both indirect (necro-inflammation and regeneration injury) and direct (by integration of its DNA in the host genome) pathways. During recent years it has become evident that HBV viral load >2000 IU/mL is associated with a high risk of malignant transformation. The most effective measure of prevention of HBV-related HCC is prevention of HBV infection by vaccination. A universal vaccination program in Taiwan was shown to be effective in reducing the rate of childhood and early adulthood HCC. In patients already infected with HBV, antiviral therapy remains the best strategy. Interferon-alfa therapy appears to be effective in preventing HCC in cirrhosis in Asia but not in Europe. Medium-term nucleos/tide-analogue therapy significantly reduces but does not eliminate the risk of HCC, especially in patients with pre-existing cirrhosis. Maintenance of virological remission is important for the reduction of HCC risk. With more potent antiviral drugs currently available (entecavir, tenofovir), long-term HBV DNA suppression is now possible with very low risk of drug resistance.