It is relatively rare for hepatocellular carcinoma (HCC) to develop in patients that are serologically negative for hepatitis B virus surface antigen (HBsAg) or anti-hepatitis C virus antibody (HCV-Ab). In addition, hepatitis B virus (HBV) is sometimes detected and associated with hepatocarcinogenesis in HCC cases without HBsAg and HCV-Ab (NBNC-HCC). In this study we focused on the characteristics of resected NBNC-HCC, and occult HBV infection in resected liver tissues was also examined in these cases. A total of 32 cases (26 males and 6 females, median age 65.7±13.9 years) that underwent liver resection were enrolled in this study. Clinical data from 19 cases with NBNC-HCC were compared with those from 13 cases of HCC related to hepatitis viruses (HV-HCC). Subsequently, occult HBV infection was assessed by the detection of HBV-DNA from extracted liver tissue in NBNC-HCC. Mutation and variation were also examined by the PCR-direct sequencing method in the occult HBV cases. The average diameter of NBNC-HCC was significantly larger than that of HV-HCC. In addition, the activity and fibrosis scores of the surrounding liver tissues were significantly higher in HV-HCC. Among 19 cases of NBNC-HCC, HBV-DNA was detected in 7. Four out of the 7 cases were detected in the Pre-S/S region. The insertion of four amino acids in the α-loop region was detected in 1 case. No significant difference between the occult HBV cases and the others was found in NBNC-HCC. All cases were classified into genotype C on phylogenetic analysis. HBV-DNA was frequently detected in the liver tissues of NBNC-HCC. Thus, our data revealed that HBV may be associated with hepatocarcinogenesis in cases of occult HBV infection.

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