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

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.