Genomic mutations with amino acid substitutions of circulating hepatitis B virus found in non-B, non-C patients with hepatocellular carcinoma.
OBJECTIVE
Most hepatocellular carcinoma (HCC) in Japan is caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HBV DNA has been detected in the serum and liver tissue of some proportion of those patients who are HBs antigen-negative and HCV antibody-negative; i.e., non-B, non-C (NBNC) patients with HCC. We sought to detect HBV DNA in the serum from NBNC HCC cases and to investigate genomic mutations of HBV in seronegative cases.


METHODS
The sera from 26 NBNC HCC patients were examined by polymerase chain reaction (PCR) followed by southern blotting for existence of HBV DNA. The precore/core and polymerase regions of the HBV genome in the sera from five seronegative cases were analyzed by direct sequence.


RESULTS
HBV DNA was detected in 17 of 26 patients (65.4%). Demographic factors such as age, gender, anti-HBs positivity, anti-HBc positivity, complication with cirrhosis, and excessive alcohol intake did not affect circulating HBV positivity. Genomic mutations with amino acid substitutions were detected in the polymerase and the precore regions from one of the five cases, and in the core region from four of the five cases.


CONCLUSIONS
PCR-based HBV screening is necessary in patients suffering from liver diseases of unknown etiology, although its etiological importance and benefit of viral elimination have not been established. Genomic mutations in the precore/core and the polymerase region detected in this study might be involved in the lack of HBsAg in NBNC HCC cases.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo.
Nobuhiro
N
Nakamoto
Hidetsugu
H
Saito
Hirotoshi
H
Ebinuma
Shinichiro
S
Tada
Yoshimasa
Y
Saito
Satoshi
S
Kurita
Kumi
K
Kitamura
Hiromasa
H
Ishii
D019943:Amino Acid Substitution; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000821:virology*; D018937:Hepatitis C Antibodies / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D012367:RNA, Viral