title: Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late.
abstract: BACKGROUND
  We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C.
  
  
  METHODS
  Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12.
  
  
  RESULTS
  Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed.
  
  
  CONCLUSIONS
  All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.
authors.affiliation: Liver Unit, San Camillo Forlanini Hospital, Rome, Italy. Electronic address: adriano.pellicelli@tiscali.it.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: Pellicelli
authors.affiliation: Liver Unit, Istituto Nazionale Malattie Infettive Spallanzani, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Montalbano
authors.affiliation: Liver Unit, Istituto Nazionale Malattie Infettive Spallanzani, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lionetti
authors.affiliation: Division of Infectious Diseases, John Hopkins University, Baltimore, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Durand
authors.affiliation: Internal Medicine and Gastroenterology, University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Liver Unit, Istituto Nazionale Malattie Infettive Spallanzani, Rome, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
authors.affiliation: Internal Medicine, Goethe University Hospital, Frankfurt, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Knop
authors.affiliation: Liver Unit, Tor Vergata University, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Telese
authors.affiliation: Liver Unit, Tor Vergata University, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lenci
authors.affiliation: Liver Unit, San Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Andreoli
authors.affiliation: Internal Medicine, Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Liver Unit, Tor Vergata University, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates; D057176:Compassionate Use Trials; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011759:Pyrrolidines; D012008:Recurrence; D012720:Severity of Illness Index; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014542:Uridine Monophosphate; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: Cholestatic hepatitis; Cirrhosis; Daclatasvir; Direct antiviral agents; Disease recurrence; HCV; MELD; Sofosbuvir