Mechanism of emergence of hepatitis C virus with resistance-associated substitution after liver transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kobe University (2019); Kyoto University (2017-2018)
• Principal Investigator: Ueda Yoshihide 神戸大学, 医学研究科, 特命教授 (90378662)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: C型肝炎 / 肝移植 / direct acting antiviral / 耐性変異

Outline of Final Research Achievements

Efficacy and safety of 12-week-regimen of sofosbuvir and ledipasvir, and 8- or 12-week regimen of glecaprevir and pibrentasvir were efficacious and safe in patients with recurrent hepatitis C after liver transplantation in our institution and in Japanese multicenter analysis. Diversity of HCV RNA in post-liver transplant and non-liver transplant patients were analyzed by using third-generation sequencing technique. We revealed that multi-drug resistant HCV clones at treatment failure originated from a subpopulation of pre-existing HCV with resistance-associated substitution, and those HCV were selected for and became dominant with the acquisition of multiple resistance-associated substitutions.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

C型肝炎ウイルス（HCV）による肝硬変・肝癌症例に対して肝移植が行われた場合には、ほぼ全例で移植後にC型肝炎が再発すること、再発後の進行が速いこと、抗HCV治療の効果が低く副作用が多いことから、肝移植後の長期生存率が低いことが明らかになっていた。本研究では、新しい抗HCV治療が肝移植後C型肝炎に対しても効果的で安全であることを明らかにした。さらに、治療不成功の原因となる薬剤耐性ウイルス出現の機序を、新しい遺伝子解析技術を用いて明らかにした。今後、肝移植後の生存率の向上が期待できる。