title: Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C.
abstract: Recurrent HCV infection following liver transplantation can lead to accelerated allograft injury that is difficult to treat with interferon. The aim of this study is to describe the first ever use of an interferon-free, all oral regimen in a liver transplant recipient with severe recurrent HCV. A 54-year-old male with HCV genotype 1b developed severe cholestatic HCV at 6 months posttransplant with ascites, AST 503 IU/mL, alkaline phosphatase of 298 IU/mL, HCV RNA of 12 000 000 IU/mL, and histological cholestasis with pericellular fibrosis. Sofosbuvir, an HCV polymerase inhibitor (400 mg/day), and daclatasvir, an HCV NS5A replication complex inhibitor (60 mg/day), were co-administered for 24 weeks. Within 4 weeks of initiating treatment, serum HCV RNA levels became undetectable and liver biochemistries normalized with concomitant resolution of ascites. The patient achieved a sustained virological response with undetectable HCV RNA at 9 months posttreatment. During and following treatment, the daily dose and blood level of tacrolimus remained stable and unchanged. The rapid and sustained suppression of HCV replication in this liver transplant recipient provides great promise for the use of combination oral antiviral regimens in other immunosuppressed and interferon refractory HCV patients.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Princeton, NJ, USA. rfontana@med.umich.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: E A
authors.initials: EA
authors.lastname: Hughes
authors.forename: M
authors.initials: M
authors.lastname: Bifano
authors.forename: H
authors.initials: H
authors.lastname: Appelman
authors.forename: D
authors.initials: D
authors.lastname: Dimitrova
authors.forename: R
authors.initials: R
authors.lastname: Hindes
authors.forename: W T
authors.initials: WT
authors.lastname: Symonds
mesh_terms: D002219:Carbamates; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D000069474:Sofosbuvir; D014184:Transplantation, Homologous; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012367:RNA, Viral; D014542:Uridine Monophosphate; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir