Ledipasvir–sofosbuvir and sofosbuvir plus ribavirin in patients with chronic hepatitis C and bleeding disorders

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2017-03, Vol.23 (2), p.198-206
• Main Authors: Walsh, C. E., Workowski, K., Terrault, N. A., Sax, P. E., Cohen, A., Bowlus, C. L., Kim, A. Y., Hyland, R. H., Han, B., Wang, J., Stamm, L. M., Brainard, D. M., McHutchison, J. G., Drygalski, A., Rhame, F., Fried, M. W., Kouides, P., Balba, G., Reddy, K. R.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Benzimidazoles - administration & dosage; Benzimidazoles - therapeutic use; Bleeding; Chronic infection; Diarrhea; Drug Combinations; Factor IX deficiency; Fatigue; Female; Fluorenes - administration & dosage; Fluorenes - therapeutic use; Genotype & phenotype; Headache; Hemophilia; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Humans; Infections; Interferon; ledipasvir–sofosbuvir fixed‐dose combination; Lentivirus; Liver; Male; Middle Aged; Nausea; NS5A inhibitor; NS5B inhibitor; Retroviridae; Ribavirin; Ribavirin - administration & dosage; Ribavirin - therapeutic use; Sleep disorders; sofosbuvir; Sofosbuvir - administration & dosage; Sofosbuvir - therapeutic use; Treatment Outcome; Young Adult
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.13178

Introduction 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. Aim 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. Conclusion 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.