Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus

Serological research suggests that hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with the development of hepatocellular carcinoma (HCC). It is unclear how genes of hepatitis viruses participate in hepatocarcinogenesis in patients infected with HCV. We investigated the expression of hepatitis virus-related RNAs in resected liver from 51 patients with HCV antibodies (Ab) and without hepatitis B surface antigen (HBsAg). mRNA transcripts of the genes HBx, HBc, HBs, nonstructural (NS) region 3 of HCV, the 5'-untranslated region (UTR) of HCV, and the 5'-UTR of hepatitis G virus (HGV) were amplified by reverse-transcription polymerase chain reaction (RT-PCR) with specific primers for each gene. The HBx transcript was detected in 19 (37%) tumors and in 8 (16%) specimens of noncancerous tissues (P =.014). The NS3 gene of HCV was detected in 35 (69%) tumors and 41 (80%) noncancerous tissues. HGV RNA was detected in 3 tumors (6%). Patients with HBx transcripts were younger than patients without HBx transcripts (P =.012). HBx transcripts were detected in 3 (33%) of 9 well-differentiated HCCs, in 8 (31%) of 26 moderately differentiated HCCs, and in 8 (50%) of 16 poorly differentiated HCCs. Codon 130 (AAG) and codon 131 (GTC) of HBx were changed to ATG and ATC, respectively, in all HCCs with HBx transcripts. In conclusion, we found that the HBx gene was expressed in many HCCs; the gene might promote hepatocarcinogenesis in patients with HCVAb and without HBsAg, but HGV is not closely related to hepatocarcinogenesis in such patients.