Association of human hepatocellular carcinoma and cirrhosis with hepatitis B virus surface and core antigens in the liver

Abstract

Paraffin sections of livers obtained at autopsy from 50 cases of hepatocellular carcinoma (HCC), 58 cases of cirrhosis and 54 cases of other miscellaneous liver disorders (controls) were stained for both surface (HBsAg) and core (HBcAg) components of hepatitis B virus (HBV) by immunoperoxidase and immunofluorescence techniques and rigidly controlled for antigen specificity, and in addition stained by orcein for HBsAg. The material was collected from different regions of India and adequate amounts of tissue were examined in most specimens to overcome possible sampling error caused by random distributions of the antigens in liver. HBsAg was detected in 94% of HCC, 71% of cirrhosis and only 2% of control livers, while HBcAg was found in 22%, 31% and none respectively. Antigen positivity seems to be directly related to the amount of tissue examined. Peroxidase staining detected smaller amounts of HBcAg than fluorescence and was also much more convenient for identifying the antigen. Both antigens were present in 9 of 41 HCC cases, 12 of 39 cirrhosis and none of 25 controls. Most of these livers contained 1+ HBsAg and 1+ to 2+ HBcAg, an antigen expression pattern suggestive of a carrier state or, rarely, of mild chronic liver disease. Among all livers tested, HBsAg alone was present in 48, both antigens were found in 21, and HBcAg alone in none. HBsAg was seen inside tumour cells in four cases, but no tumour showed HBcAg. Most HCC was associated with cirrhosis (92%) and antigen-positive cirrhosis had a higher chance of harbouring HCC than antigen-negative disease. HBsAg was detected in all four non-cirrhotic livers associated with HCC, while two of these also had HBcAg. Active cirrhosis was very frequently associated with HBsAg. These results and the overwhelming evidence of sero-logical and epidemiological studies from various parts of the world suggest a strong association of the hepatitis B virus with HCC. The possible ways in which the two could be related are discussed.