Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan.

We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.