Hepatitis B virus surface and core antigens (HBsAg, HBcAg) were examined in the resected primary hepatocellular carcinoma from 204 patients who had HBsAg in serum. Ninety patients had small (<5 cm) and 114 had large hepatocellular carcinoma (>5 cm). HBsAg was detected in hepatocellular carcinoma in 65 cases (32%) and HBcAg in 30 cases (14.7%); hepatitis B virus antigens were more frequently detected in small (HBsAg in 42.2% and HBcAg in 20%) than in large hepatocellular carcinoma (HBsAg 23.7% and HBcAg 10.5%). These results suggest that replicative forms of hepatitis B virus DNA may exist in hepatocellular carcinoma more frequently than previously believed and that the malignant hepatocytes can support hepatitis B virus replication. A lymphocytic infiltration in hepatocellular carcinoma was more often observed in hepatocellular carcinoma expressing HBsAg (71%) or HBcAg (63%) than in hepatocellular carcinoma with no detectable HBsAg (26%) or HBcAg (37%), p < 0.01. The reaction was mild in the majority (85%) of the cases. These findings suggest that hepatitis B virus antigen expression in hepatocellular carcinoma can provoke a local immune response. The most striking finding was that patients with hepatitis B virus antigens in small hepatocellular carcinoma had a 5‐year survival rate (13%) lower than that (50%) of the antigen‐negative patients (p < 0.05). In contrast, patients with a marked local immune response in hepatocellular carcinoma, regardless of the viral antigen status, had significantly better 5‐year survival rates (43%) than those with no or a mild lymphocytic reaction (18%). These findings indicate that a marked immune response in hepatocellular carcinoma is a favorable prognostic sign. The unfavorable course of the patient with viral antigen‐expressing hepatocellular carcinoma may in fact reflect the inability of the host immune response to clear the viral infection and the antigen‐expressing tumor cells.
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