Antivirals Effective in Patients With HCV Infection and Hemophilia

Treatment with direct-acting antivirals (DAAs) is safe and effective in patients with chronic hepatitis C virus (HCV) infection and inherited bleeding disorders, according to a study published in Haemophilia.¹

Hepatic complications related to HCV infection are a leading cause of death in patients with hemophilia. DAAs have been shown to induce high rates of sustained virologic response (SVR) in patients with chronic HCV infection, but clinical trials have generally excluded patients with inherited bleeding disorders given their risk of unique adverse events and inability to undergo liver biopsy due to bleeding risk.¹ While few studies evaluating DAAs in patients with hemophilia are available, the phase 2 ELECTRON study found that ledipasvir-sofosbuvir fixed-dose combination plus ribavirin induced SVR in 100% of patients with hemophilia and HCV genotype 1 infection.²

Christopher E. Walsh, MD, PhD, from Mount Sinai Hospital in New York, and colleagues evaluated the safety and efficacy of ledipasvir-sofosbuvir fixed-dose combination for HCV genotype 1 and 4 infection and sofosbuvir plus ribavirin for HCV genotype 2 and 3 infection in patients with inherited bleeding disorders.¹

In this phase 2b open-label trial, 104 patients had HCV genotype 1 or 4 infection and 16 had HCV genotype 2 or 3 infection. More than 90% of patients had hemophilia A or B, and more than half of all patients had a bleeding disorder that was considered severe. The majority of patients had not received prior treatment for HCV.¹

Patients with genotype 1 or 4 infection were treated with ledipasvir-sofosbuvir for 12 or 24 weeks. Sofosbuvir plus ribavirin was administered to patients with genotype 2 for 12 weeks and to patients with genotype 3 for 24 weeks.¹

SVR at 12 weeks after treatment (SVR12) was 99% and 100% in patients with genotype 1 or 4 infection receiving ledipasvir-sofosbuvir for 12 and 24 weeks, respectively. Sofosbuvir plus ribavirin induced SVR12 in 100% of patients with genotype 2 and 83% of patients with genotype 3 infection.¹

Treating for 24 weeks did not increase the risk for adverse events compared with treating for 12 weeks with both regimens. A total of 22 patients experienced bleeding events, which were not considered treatment-related. Fatigue was the most common nonbleeding adverse event for both regimens.¹

“For patients with bleeding disorders who have contracted HCV, treatment with DAAs is curative, and these patients should actively seek treatment,” Dr Walsh told Infectious Disease Advisor.

While DAAs may induce SVR in the majority of patients with hemophilia with HCV, Dr Walsh acknowledged that the long-term effects of treatment remain unknown. “We don’t know the long-term outcomes of patients treated for HCV in terms of developing liver cancer and liver failure. We also don’t know how well patients with liver cirrhosis due to HCV will improve over time,” he said. “These are areas that may require further investigation.”

References

1. Walsh CE, Workowski K, Terrault NA, et al. Ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic hepatitis C and bleeding disorders. [published online January 25, 2017] Haemophilia. doi:10.1111/hae.13178
2. Stedman CA, Hyland RH, Ding X, Pang PS, McHutchison JG, Gane EJ. Once daily ledipasvir/sofosbuvir fixed-dose combination with ribavirin in patients with inherited bleeding disorders and hepatitis C genotype 1 infection. Haemophilia. 2016;22:214-217. doi:10.1111/hae.12791