Toru Ikegami1, Tomoharu Yoshizumi, Masaki Kato, Satomi Yamamoto, Takasuke Fukuhara, Yoshiharu Matsuura, Shota Nakamura, Shinji Itoh, Ken Shirabe, Yoshihiko Maehara. 1. 1 Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. 2 Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. 3 Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 4 Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 5 Address correspondence to: Toru Ikegami, M.D., Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
Abstract
INTRODUCTION: The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients. METHODS: Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy. RESULTS: Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4-20 U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36. CONCLUSIONS: Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis.
INTRODUCTION: The feasibility of telaprevir-based triple therapy for recurrent hepatitis C after liver transplantation (LT) has not been evaluated in Asian patients. METHODS: Eleven Japanese patients received reduced-dose telaprevir (1500 mg) and adjusted-dose cyclosporine after LT. Six patients were nonresponders and three were transient responders to dual therapy. RESULTS: Rapid viral response, early viral response, end of treatment response, and sustained viral response were achieved in 27.3%, 90.9%, 90.9%, and 81.8% of patients, respectively. One patient had viral breakthrough at week 8 with a T54A mutation in NS3. Deep sequence analysis showed that the T54A mutation reverted to wild-type after stopping telaprevir administration. Seven patients developed severe anemia, and six received blood transfusions (4-20 U). Their hemoglobin and estimated glomerular filtration rate remained significantly lower than pretreatment values at 36 weeks after treatment. Four patients developed plasma cell hepatitis after completing telaprevir treatment, and it was treated by increasing the immunosuppressants. Although the cyclosporine level/dose ratio was 2.7 times higher at week 4 than before treatment, it was 0.7 times lower at week 36. CONCLUSIONS: Reduced-dosed telaprevir-based triple antiviral therapy achieved a high viral clearance rate in Japanese patients after LT. Major adverse events included severe anemia, renal dysfunction, and plasma cell hepatitis.
Authors: Fritz Klein; Ruth Neuhaus; Dennis Eurich; Jörg Hofmann; Sandra Bayraktar; Johann Pratschke; Marcus Bahra Journal: Hepat Res Treat Date: 2016-04-18