Hepatitis B virus DNA in human hepatocellular carcinoma: is the integration of hepatitis B virus DNA really carcinogenic?

Hepatitis B virus-specific DNA sequences (HBVDNA) in the liver were examined in 19 patients with hepatocellular carcinoma (HCC), 5 patients with liver cirrhosis (LC) and without HCC, 3 patients with chronic hepatitis (CH), 2 patients with metastatic liver cancer (MLC), 1 patient with primary biliary cirrhosis (PBC) and 4 patients with normal liver (NL) by the Southern blot hybridization procedure. Integration of HBVDNA was found in all 4 HCC patients with serum HBsAg, of whom one patient had HBVDNA only in the non-tumor (cirrhotic) region. Integration of HBVDNA was also detected in 4 of 8 HCC patients without serum HBsAg but with serum HBV-related antibodies, and in 2 HBsAg-positive patients of 5 LC patients. All 3 HBsAg-positive CH patients had only extrachromosomal HBVDNA. No HBVDNA was detected in the other 21 patients. Although integration of HBVDNA was observed in HBsAg-positive HCC patients with a higher frequency, integrated HBVDNA could also be detected in non-tumor regions of HCC patients and cirrhotic livers without HCC. It was concluded from these observations that integration of HBVDNA was frequently associated with HCC but might not have a direct causal effect on hepatocarcinogenesis even in HBV carriers.