Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection
Article first published online: 19 MAY 2008
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 29, Issue 1, pages 126–132, January 2009
How to Cite
Hayashi, T., Tamori, A., Nishikawa, M., Morikawa, H., Enomoto, M., Sakaguchi, H., Habu, D., Kawada, N., Kubo, S., Nishiguchi, S. and Shiomi, S. (2009), Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection. Liver International, 29: 126–132. doi: 10.1111/j.1478-3231.2008.01772.x
- Issue published online: 12 DEC 2008
- Article first published online: 19 MAY 2008
- Received 16 January 2008Accepted 16 March 2008
- hepatitis C virus;
- hepatocellular carcinoma;
- mitochondrial DNA;
- sustained virological response
Background/Aims: The mechanism of hepatocarcinogenesis remains unclear in patients in whom hepatitis C virus (HCV) disappears after interferon (IFN) therapy. We compared molecular alterations in hepatocellular carcinoma (HCC) between patients with a sustained virological response (SVR) to IFN and patients with HCV.
Methods: The study group comprised 44 patients with HCV and 13 patients with SVR. One patient in the SVR group had two tumour nodules, both of which were examined. Mitochondrial DNA (mtDNA) mutations in displacement-loop lesions were directly sequenced. Mutation of the TP53 gene was examined by direct sequencing. The methylation status of p16, p15, p14, RB and PTEN genes was evaluated by a methylation-specific polymerase chain reaction.
Results: The average number of mtDNA mutations was 4.2 in 44 HCCs with HCV and 2.0 in 14 HCCs with SVR (P=0.0021). mtDNA mutation was less frequently detected in HCCs from patients with SVR than in patients with HCV. TP53 mutations were detected in 12 (27%) of 44 HCCs with HCV and 2 (14%) of 14 SVR-HCCs. Hypermethylation of the p16, p15, p14, RB and PTEN promoters was, respectively, detected in 34, 13, 8, 12 and 11 of 44 HCCs from patients with HCV and 14, 0, 0, 2 and 2 of 14 HCCs from patients with SVR (P=0.049, 0.021, 0.085, 0.322 and 0.402). Hypermethylation of p16 was one of the most important alterations in SVR-HCC.
Conclusions: Molecular alterations in hepatocarcinogenesis of patients with SVR-HCC were different from those of patients with continuous HCV infection.