About
Prof. Yasuhito Tanaka
Head Department of Virology and Liver Unit
Nagoya City University Graduate School of Medical Sciences, Japan
“Genome-wide association study on Viral hepatitis C and hepatocellular carcinoma”
Jeudi 12 Avril 2018 à 11h30
Salle Jean-Paul Aubert, Bâtiment Fernbach
Abstract :
“The clinical course of hepatitis C virus (HCV) infection greatly differs in individuals. Various viral, host, and environmental factors influence the natural history of HCV infection. Recent genome-wide association studies (GWAS) identified several host genetic factors influencing treatment efficacy or clinical course in HCV infection. A landmark discovery was that IFNL3 (IL28B)-IFNL4 variants are strongly associated with responses to interferon-based treatment (Tanaka Y. et al. Nat Genet 2009). Genetic variants in IFNL3-IFNL4 as well as those in HLA class II loci influence the spontaneous clearance of acute HCV infection. Interestingly, these genetic variants also affect the activity of hepatitis or disease progression in chronic hepatitis C. The risk of developing hepatocellular carcinoma (HCC) will not completely disappear even after the eradication of HCV by anti-viral therapy. Recently, we reported that SNP rs17047200, located within the intron of TLL1 on chromosome 4, showed a strong association with developing HCC at a genome-wide level of significance when the results of the GWAS and the replication cohort were combined (odds ratio = 2.37, P = 2.66 × 10-8) (Matsuura K. et al. Gastroenterology 2017). Combining the rs17047200 genotype with other factors, we propose different prediction models for HCC development in patients with mild or advanced hepatic fibrosis. TLL1 expression analyses showed that mRNA levels in human stellate cells increased with activation. Moreover, Tll1/TLL1 mRNA increased in liver tissues of rodents with hepatic fibrogenesis and CHC patients with progression of hepatic fibrosis. In conclusion, TLL1 may contribute to HCC development mainly via hepatic fibrogenesis, and the genetic testing for the TLL1 SNP would be used to identify patients at risk for HCC after achieving SVR.”
Invited by Yusuke Shimakawa (yusuke.shimakawa@pasteur.fr) & Arnaud Fontanet (fontanet@pasteur.fr)
Institut Pasteur – 25, 28, rue du Dr. Roux– 75724 PARIS CEDEX 15