title: Efficacy and Safety of Therapy With Simeprevir and Sofosbuvir in Liver Transplant Recipients Infected by Hepatitis C Virus Genotype 4: Cohort Spanish Society of Liver Transplantation Cohort.
abstract: BACKGROUND
  Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of 2nd-generation direct-acting antivirals (DAAs), and more data are needed to help guide treatment decisions. We still have even fewer data concerning liver transplant patients. Simeprevir (SIM) and sofosbuvir (SOF) combination is useful to treat this genotype. The aim of this study was to know the efficacy and safety of the combination SIM + SOF ± ribavirin (RBV) in a group of liver transplant patients with HCV genotype 4 infection in Spain in real life.
  
  
  METHODS
  This was a multicenter retrospective study, including 28 HCV genotype 4 patients from 11 liver transplant centers who were treated with SIM + SOF ± RBV. We included in the analysis demographic, clinical, and virologic data and details of serious adverse events (SAEs), including mortality rate 6 months after treatment.
  
  
  RESULTS
  All patients were male, mean age 52 ± 9.43 years, and 50% were IL28B CT and 37.5% TT; 46.42% of them were pretreated and 76.9 were null responders. Fibrosis stage 4 was found in 38.7% of patients; in 67.8% of those cases the diagnosis of fibrosis was made with the use of Fibroscan, in 21.4% by liver biopsy. The average Fibroscan was 13.86 KPa. The average Model for End-Stage Liver Disease (MELD) score of cirrhotic patients was 10.9 and the Child-Pugh score was A in 70%, B in 20%, and C in 10%. We included RBV in 75% of patients, and treatment duration was 12 weeks in all patients. The sustained virologic response at week 12 (SVR12) was 95.23%. There were no discontinuations due to SAEs, but the mortality rate at 6 months after treatment was 7.14%. All deceased patients were cirrhotic, Child C, and with an average MELD score of 20.
  
  
  CONCLUSIONS
  The combination SIM + SOF ± RBV to treat HCV genotype 4 in liver transplant patients is an option with high rates of SVR12 and very safe, similarly to genotype 1. There was no treatment-related mortality, but when it is administered in advanced stages of fibrosis it may not be enough to prevent mortality associated with cirrhotic hepatitis C recurrence after transplantation.
authors.affiliation: Hepatology Unit, Liver Transplant Unit, Hospital Universitario Rio Hortega, Valladolid, Spain. Electronic address: gloriasanchez_antolin@hotmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Sanchez Antolin
authors.affiliation: Hepatology Unit, Liver Transplant Unit, Hospital Universitario Cruces, Bilbao, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Testillano
authors.affiliation: Hepatology Unit, Hospital Universitario Virgen del Rocio, CIBERhed, Sevilla, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Pascasio
authors.affiliation: Gastroenterology Service, Liver Transplant Unit Hospital Infanta Cristina, Badajoz, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Narvaez Rodriguez
authors.affiliation: Hepatology Unit, Hospital, Liver Transplant Unit Universitario La Fe, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Prieto
authors.affiliation: Liver Transplant Unit, Hospital Universitario Juan Canalejo, La Coruña, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Otero
authors.affiliation: Service of Internal Medicine, Liver Transplant Unit, CUN, Pamplona, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Herrero
authors.affiliation: Hepatology Service, Liver Transplant Unit, Hospital Clinic, CIBERhed, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Londoño
authors.affiliation: Service of Gastroenterology, Hepatology Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Fernandez Vazquez
authors.affiliation: Service of Hepatology, CIBERhed Hospital Universitario, Vall d'Hebrón, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Castells
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*; D013030:Spain; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir