International Session (Symposium)1(JSH・JSGE・JSGCS)
November 3 (Thu.), 9:00–12:00, Room 8 (Portopia Hotel Main Building Kairaku 2)

Genome-wide association study on developing hepatocellular carcinoma after eradication of hepatitis C virus

K. Matsuura1,2
Co-authors: K. Tokunaga3, Y. Tanaka1
Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo
Aims: We aimed to identify host genetic variations associated with developing hepatocellular carcinoma (HCC) after the eradication of hepatitis C virus (HCV). Methods: We conducted a genome-wide association study (GWAS) in 456 Japanese chronic hepatitis C patients who achieved sustained virological response (SVR) by interferon-based therapy, then selected 70 candidate single nucleotide polymorphisms (SNPs) to carry out a replication analysis in an independent set of 486 patients. Results: The SNP0014, on chromosome 4, showed a strong association with developing HCC in a genome-wide level of significance when the results of GWAS and the replication stage were combined (OR = 2.37, P = 2.66 x 10-8). Multivariate analysis with stepwise Cox proportional hazard model showed that SNP0014 genotype was independently associated with developing HCC (HR = 1.86, P = 0.002) as well as male gender, elder age, lower platelet count and albumin level, and higher post-treatment α-fetoprotein level. In combination of SNP0014 genotype with distinct other factors, we could propose each prediction model for developing HCC in patients with mild and advanced hepatic fibrosis. Conclusion: Genetic testing of this variant would be useful for implementing personalized surveillance of HCC after achieving SVR.
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