title: Ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic hepatitis C and bleeding disorders.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is prevalent among patients with inherited bleeding disorders and is a leading cause of mortality in those with haemophilia.
  
  
  OBJECTIVE
  We evaluated the efficacy and safety of ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic HCV genotype 1-4 infection and an inherited bleeding disorder.
  
  
  METHODS
  Ledipasvir-sofosbuvir was administered for 12 weeks to patients with genotype 1 or 4 infection and for 12 or 24 weeks to treatment-experienced cirrhotic patients with genotype 1 infection. Patients with genotype 2 and 3 infection received sofosbuvir plus ribavirin for 12 and 24 weeks respectively.
  
  
  RESULTS
  The majority of the 120 treated patients had a severe bleeding disorder (55%); overall, 65% of patients had haemophilia A and 26% of patients had haemophilia B; 22% were HIV coinfected. Sustained virologic response at 12 weeks posttreatment was 99% (98/99) in patients with genotype 1 or 4 infection; 100% (5/5) in treatment-experienced cirrhotic patients with genotype 1 infection; 100% (10/10) in patients with genotype 2 infection; and 83% (5/6) in patients with genotype 3 infection. There were no treatment discontinuations due to adverse events (AEs). The most frequent non-bleeding AEs were fatigue, headache, diarrhoea, nausea and insomnia. Bleeding AEs occurred in 22 patients, of which all but one were considered unrelated to treatment.
  
  
  CONCLUSIONS
  Treatment with ledipasvir-sofosbuvir for patients with HCV genotype 1 or 4 infection or sofosbuvir plus ribavirin for patients with genotype 2 or 3 infection was highly effective and well tolerated among those with inherited bleeding disorders.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY, USA.
authors.forename: C E
authors.identifier: http://orcid.org/0000-0001-5378-9656
authors.initials: CE
authors.lastname: Walsh
authors.affiliation: Emory University, Atlanta, GA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Workowski
authors.affiliation: University of California at San Francisco, San Francisco, CA, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Terrault
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Sax
authors.affiliation: Newark Beth Israel Medical Center, Barnabas Health, Newark, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cohen
authors.affiliation: University of California at Davis, Davis, CA, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Bowlus
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Gilead Sciences Inc., Foster City, CA, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Hyland
authors.affiliation: Gilead Sciences Inc., Foster City, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.affiliation: Gilead Sciences Inc., Foster City, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Gilead Sciences Inc., Foster City, CA, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Stamm
authors.affiliation: Gilead Sciences Inc., Foster City, CA, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences Inc., Foster City, CA, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: University of California at San Diego, San Diego, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: von Drygalski
authors.affiliation: Abbott Northwestern Hospital, Minneapolis, MN, USA.
authors.forename: F
authors.initials: F
authors.lastname: Rhame
authors.affiliation: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Fried
authors.affiliation: The Mary M. Gooley Hemophilia Center, Rochester, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kouides
authors.affiliation: MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Balba
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: NS5A inhibitor; NS5B inhibitor; hepatitis C virus; ledipasvir-sofosbuvir fixed-dose combination; ribavirin; sofosbuvir