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》

The role of previous infection of hepatitis B virus in Hbs antigen negative and anti-HCV negative Japanese patients with hepatocellular carcinoma: etiological and molecular biological study.

Matsuzaki Y ，Sato M ，Saito Y ，Karube M ，Doy M ，Shoda J ，Abei M ，Tanaka N ，Hadama T ，Kinoshita M ... -  《-》

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》

Sequencing of human-viral DNA junctions in hepatocellular carcinoma from patients with HCV and occult HBV infection.

DNA of free hepatitis B viruses (HBV) has been detected in the liver of patients infected with hepatitis C virus (HCV). It is unknown whether HBV DNA is integrated into such livers; if so, it may affect hepatocarcinogenesis. Hepatocellular carcinomas (HCCs) from 34 patients without HBV surface antigen (HBsAg) and with anti-HCV, and from 7 patients with HBsAg and without anti-HCV as controls, were examined, using the cassette-ligation-mediated polymerase chain reaction and primers based on HBV DNA sequence. In the controls, HBV DNA had been integrated into human DNA of all HCCs. On the basis of HBV DNA in tumor tissue, 23 of the 34 patients with anti-HCV had occult infection. Junctions between human DNA and HBV DNA were detected in 10 of the 34 patients without HBsAg and with anti-HCV. HBV DNA was integrated into chromosome 11q in 4 of the 10 HCCs with junctions. The DNA to either side of the human-viral junctions was sequenced. Clinically, the mean tumor size of these 10 HCCs was 39 mm; that of the 24 HCCs without integrated HBV was 25 mm. The surrounding tissue was cirrhotic in 2 of the 10 former HCCs and in 16 of the latter 24 HCCs. In conclusion, integrated HBV was detected in some patients with HCV infection; in these patients, the integrated DNA was associated with accelerated hepatocarcinogenesis.

Tamori A ，Nishiguchi S ，Kubo S ，Enomoto M ，Koh N ，Takeda T ，Shiomi S ，Hirohashi K ，Kinoshita H ，Otani S ... -  《JOURNAL OF MEDICAL VIROLOGY》

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》