title: Reduced-dose telaprevir-based triple antiviral therapy for recurrent hepatitis C after living donor liver transplantation.
abstract: BACKGROUND
  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.affiliation: 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.
authors.forename: Toru
authors.initials: T
authors.lastname: Ikegami
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Satomi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Shinji
authors.initials: S
authors.lastname: Itoh
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000150:complications; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage; D058625:End Stage Liver Disease / Q000208:ethnology / Q000601:surgery*; D005260:Female; D005919:Glomerular Filtration Rate; D006239:Haplotypes; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007564:Japan; D016031:Liver Transplantation / Q000009:adverse effects; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D009842:Oligopeptides; D012367:RNA, Viral; C486464:telaprevir; D016572:Cyclosporine