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.
Bibliographical noteFunding Information:
The authors extend their thanks to the patients who participated in this study, as well as their families, and to the staff at the Hemophilia Treatment Centers who supported this study. Christopher E. Walsh, Robert H. Hyland, Luisa M. Stamm, Diana M. Brainard, John G. McHutchison and K. Rajender Reddy contributed to the design of the study. Christopher E. Walsh, Kimberly Workowski, Norah A. Terrault, Paul E. Sax, Alice Cohen, Christopher L. Bowlus, Arthur Y. Kim, Annette von Drygalski, Frank Rhame, Michael W. Fried, Peter Kouides, Gayle Balba and K. Rajender Reddy contributed to data collection. Jing Wang and Bin Han contributed to data analysis. All authors reviewed and approved the manuscript prior to submission. Writing and editorial support was provided by Sameera Kongara of AlphaBioCom, LLC, King of Prussia, PA, and funded by Gilead Sciences, Inc. This study was funded by Gilead Sciences, Inc.
- hepatitis C virus
- ledipasvir–sofosbuvir fixed-dose combination
- NS5A inhibitor
- NS5B inhibitor