Molecular and serological aspects of HBsAg-negative hepatitis B virus infections in North America.

A few hepatitis B virus (HBV) infections are characterized by the presence of HBV DNA in serum or liver tissue, or both, in the absence of detectable hepatitis B surface antigen (HBsAg) in serum. However, such infections have rarely been described previously in North American patients. In the present study, 31 hepatocellular carcinoma (HCC) patients from the United States and Canada who had no detectable HBsAg in their serum were studied. In these 31 HBsAg-negative HCC patients, HBV DNA was detected in HCC and/or in adjacent nontumorous liver tissue using nested polymerase chain reaction (PCR) in 5/9 (56%) patients from the United States and in 12/22 (55%) from Canada. The 17 HBV DNA-positive/HBsAg-negative patients from the United States and Canada included 9 without any serological markers for HBV and 8 with detectable antibodies to hepatitis B core antigen. In these patients, HBV genotype C was the most prevalent genotype (11/17; 64%). HBV genotypes have not been previously reported in HCC patients from North America. Replicative intermediate forms of HBV (covalently closed circular HBV DNA) were detected in 2/17 (12%) HBV DNA-positive/HBsAg-negative patients, indicating that at least two of these patients had actively replicating HBV infections. The use of tests to detect HBV DNA permitted the identification of HBV infections in HBsAg-negative HCC patients from North America. Among these patients, those with antibody to hepatitis C virus (HCV) would otherwise have been designated "HCV-associated HCCs" based on serological tests alone. These findings provide a new perspective on determining the possible viral etiologies of HCCs in North America.

Hsia CC ，Scudamore CH ，Di Bisceglie AM ，Tabor E ... -  《JOURNAL OF MEDICAL VIROLOGY》

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma.

Momosaki S ，Nakashima Y ，Kojiro M ，Tabor E ... -  《JOURNAL OF VIRAL HEPATITIS》

HBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan.

Few studies have examined the etiology of hepatocellular carcinoma (HCC) in patients without hepatitis virus infection. We evaluated the role of occult hepatitis B virus (HBV) infection in the development of HCC in Japanese patients without hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C antigen (anti-HCV). Twenty-one HBsAg negative and anti-HCV negative (non-B, non-C) patients with HCC were studied. HBV DNA in serum and HBV transcripts in liver were examined by polymerase chain reaction (PCR) or reverse transcription and PCR. HBV DNA integration was examined by Southern blot analysis or cassette-ligation-mediated PCR as described previously. p53 mutations were examined by direct sequencing. HBV DNA was not detected in serum from any patients. HBV-related transcripts were detected in 5 of 7 HCCs from patients with antibodies to hepatitis core antigen (anti-HBc) and in 3 of 14 HCCs from patients without anti-HBc (P = 0.0261). HBV DNA was integrated into human genome in two non-B, non-C HCCs. Of the 14 patients without anti-HBc, 5 had a history of excessive alcohol intake. In exons 5 through 8 of the p53 gene, mutations were detected in 2 of 8 HCCs with HBV-transcripts and in 5 of 13 HCCs without such transcripts. p53 mutation at codon 159 was found in 2 of 6 patients with excessive alcohol intake without HBV-transcripts. These results suggested that occult HBV infection might play an important role in hepatocarcinogenesis in non-B, non-C patients with anti-HBc and that excessive alcohol intake might be related to HCC in non-B, non-C patients in Japan.

Tamori A ，Nishiguchi S ，Kubo S ，Narimatsu T ，Habu D ，Takeda T ，Hirohashi K ，Shiomi S ... -  《JOURNAL OF MEDICAL VIROLOGY》

Geographic characterization of hepatitis virus infections, genotyping of hepatitis B virus, and p53 mutation in hepatocellular carcinoma analyzed by in situ detection of viral genomes from carcinoma tissues: comparison among six different countries.

Ding X ，Park YN ，Taltavull TC ，Thung SN ，Jin X ，Jin Y ，Trung NS ，Edamoto Y ，Sata T ，Abe K ... -  《JAPANESE JOURNAL OF INFECTIOUS DISEASES》

Hepatitis C and B virus infections in hepatocellular carcinoma. Analysis of direct detection of viral genome in paraffin embedded tissues.

Edamoto Y ，Tani M ，Kurata T ，Abe K ... -  《CANCER》