title: Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation.
abstract: Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12-week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%-90%). Four patients relapsed, but no on-treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child-Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12-week RBV-free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635-643 2016 AASLD.
authors.affiliation: Departments of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Crittenden
authors.affiliation: Departments of Medicine, Division of Digestive Health, University of Kentucky, Lexington, KY.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Buchanan
authors.affiliation: School of Public Health and Information Sciences, University of Louisville, Louisville, KY.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Pinkston
authors.affiliation: Departments of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.
authors.forename: Barbra
authors.initials: B
authors.lastname: Cave
authors.affiliation: Departments of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.|Robley Rex Veterans Affairs Medical Center, Louisville, KY.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Barve
authors.affiliation: Departments of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.|Robley Rex Veterans Affairs Medical Center, Louisville, KY.
authors.forename: Luis
authors.initials: L
authors.lastname: Marsano
authors.affiliation: Departments of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY.|Pharmacology and Toxicology, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.|Robley Rex Veterans Affairs Medical Center, Louisville, KY.
authors.forename: Craig James
authors.initials: CJ
authors.lastname: McClain
authors.affiliation: Surgery, Division of Transplantation, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jones
authors.affiliation: Surgery, Division of Transplantation, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Marvin
authors.affiliation: Surgery, Division of Transplantation, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Davis
authors.affiliation: Departments of Medicine, Division of Digestive Health, University of Kentucky, Lexington, KY.
authors.forename: Candice B
authors.initials: CB
authors.lastname: Kuns-Adkins
authors.affiliation: Surgery, Division of Transplantation, University of Kentucky, Lexington, KY.|Healthcare Transplant Center, University of Kentucky, Lexington, KY.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gedaly
authors.affiliation: School of Public Health and Information Sciences, University of Louisville, Louisville, KY.
authors.forename: Guy
authors.initials: G
authors.lastname: Brock
authors.affiliation: Surgery, Division of Transplantation, University of Kentucky, Lexington, KY.|Healthcare Transplant Center, University of Kentucky, Lexington, KY.
authors.forename: Malay B
authors.initials: MB
authors.lastname: Shah
authors.affiliation: Departments of Medicine, Division of Digestive Health, University of Kentucky, Lexington, KY.|Healthcare Transplant Center, University of Kentucky, Lexington, KY.
authors.forename: Jens
authors.initials: J
authors.lastname: Rosenau
authors.affiliation: Departments of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY.|Pharmacology and Toxicology, University of Louisville, Louisville, KY.|Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY.|KentuckyOne Health Transplant Center, Louisville, KY.|Robley Rex Veterans Affairs Medical Center, Louisville, KY.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cave
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007165:Immunosuppression Therapy; D008103:Liver Cirrhosis; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011110:Polymorphism, Genetic; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D000069616:Simeprevir / Q000008:administration & dosage*; D000069474:Sofosbuvir / Q000008:administration & dosage*; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir