Iron, ferritin, hepatitis B surface and core antigens in the livers of chinese patients with hepatocellular carcinoma

Abstract
Surgically resected specimens, consisting of tumor and adjacent non-neoplastic liver tissue, were obtained from 40 patients with primary liver cancer at Zhong Shah Hospital, Shanghai Medical University, the People's Republic of China, between March 1983 and July 1984. All were hepatocellular carcinomas (HCC), one being admixed with cholangiocarcinoma. The relationship of hepatitis B virus (HBV) markers with iron and ferritin was evaluated in liver tissues from patients with primary liver cancers. The serum HBsAg (Hepatitis B surface antigen) positive rate was 80.0% (32/40). Cirrhosis was observed in 97.5% (39/40). HBsAg was identified in 82.5% (33/40) of uninvolved liver, and 35.0% (14/40) of HCC tissues (P < 0.001). HBcAg (hepatitis B core antigen) was detected in 25.0% (10/40) of liver, and 7.5% (3/40) of HCC tissues (P < 0.05). Stainable iron was found in 65.0% (26/40) of unaffected livers, and 10.0% (4/40) of HCC tissues (P < 0.001). Ferritin was demonstrated in 75% (30/40) of non-neoplastic liver, and 40% (16/40) of HCC tissues (P < 0.001). Twenty-two of 33 HCC patients (66.7%) with HBsAg positive cells in their livers also showed stainable iron. Of 16 patients positive for ferritin in HCC cells, iron was found in only two. Iron was found in nine of ten patients with HBcAg in non-neoplastic hepatocytes (P = 0.056); a finding compatible with the hypothesis that iron accumulates in cells replicating HBV. The other results indicate that: (1) immunohistologic ferritin in HCC is not due to increased stainable iron; (2) tumor cells may produce ferritin; (3) polyclonal antibodies to human liver ferritin react better with non-neoplastic hepatocytes than with HCC cells; (4) the high prevalence of HBsAg and cirrhosis in HCC suggests that HBV plays a major etiologic role in hepatocarcinogenesis in China; and (5) one case of HCC is attributed to Schistosoma japonicum infestation via cirrhosis.