Analysis of HCV drug resistance associated variants treated with direct-acting antiviral (DAA) failure and genetic factors predict of HCC development after SVR.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15960
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: IIO ETSUKO 名古屋市立大学, 医薬学総合研究院(医学), 助教 (20543797)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HCV / DAA / SVR後発癌 / TLL1

Outline of Final Research Achievements

The eradication of HCV by IFN-free DAAs treatment is effective at reducing the risk of HCC. However, there is still a risk of HCC after eradicating HCV. We envestigated the host genetic risk factors of SVR-HCC. More than 1100 patients achieved SVR with IFN free DAAs treatment were enrolled. The proportion of rs17047200 AT/TT was significantly higher in the HCC group than the non-HCC group . Higher levels of a-fetoprotein, FIB-4 and rs17047200 AT/TT were independent risk factors for developing HCC. Cumulative incidence of HCC was significantly higher in patients with rs17047200 AT/TT than in those with AA. Comparing clinical characteristics according to the TLL1 genotypes, patients with rs17047200 AT/TT had significantly lower platelet counts and higher levels of FIB-4 than those with AA. The TLL1 variant was independently associated with HCC development after HCV eradication by IFN-free regimen. We reported these results with J Gastroenterol. 2019 Apr;54(4):339-346.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

HCVはIFNフリーDAA治療の進歩により、ごく一部の難治症例を除き、ほぼ全例ウイルス排除（SVR）ができる時代になり、SVR後の肝発癌高リスク群の囲い込みが重要になっている。IFN治療時代から言われていた肝硬変、高齢といった因子だけでなく、ヒトの遺伝子要因としてTLL1遺伝子多型が関与することを明らかにした。AFPやFIb4といった従来の発癌リスク因子に加えて、遺伝的要因を加味することで、多数のSVR症例の中から、発癌高リスク群の囲い込みに寄与すると思われる。今後の日常臨床において、SVR後フォローに関する重要な知見が得られたと思われる。