Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4

Background & Aims

Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection in the world, and more than 90% of patients are infected with genotype 4 virus. We evaluated the efficacy and safety of the HCV polymerase inhibitor sofosbuvir in combination with ribavirin in HCV genotype 4 patients in Egypt.

Methods

Treatment-naïve or treatment-experienced patients with genotype 4 HCV infection (n = 103) were randomly assigned to receive either 12 or 24 weeks of sofosbuvir 400 mg and ribavirin 1000–1200 mg daily. Randomization was stratified by prior treatment experience and by presence or absence of cirrhosis. The primary endpoint was the percentage of patients with HCV RNA <25 IU/ml 12 weeks after therapy (SVR12).

Results

Among all patients, 52% had received prior HCV treatment and 17% had cirrhosis at baseline. SVR12 rates were 90% (46/51) with 24 weeks and 77% (40/52) with 12 weeks of sofosbuvir and ribavirin therapy. Patients with cirrhosis at baseline had lower rates of SVR12 (63% 12 weeks, 78% 24 weeks) than those without cirrhosis (80% 12 weeks, 93% 24 weeks). The most common adverse events were fatigue, headache, insomnia, and anemia. Two patients experienced serious adverse events (cerebral ischemia, dyspnea). No adverse events resulted in treatment discontinuation.

Conclusion

Sofosbuvir plus ribavirin for 12 or 24 weeks is effective in treating both treatment-naïve and treatment-experienced Egyptian patients with genotype 4 HCV.

Introduction

Egypt has the highest prevalence of hepatitis C virus (HCV) infection in the world [1]. The prevalence of HCV viremia was estimated to be 7.3% for the year 2013 [2], [3] on the basis of data from the 2008 Egypt Demographic and Health Survey [4]. Egypt also has the greatest number of patients with genotype 4 HCV, more than 90% of those infected or approximately six million people [5]. Within the country, the prevalence of HCV varies among age groups and is highest in persons who received parenteral anti-schistosomiasis treatment in the 1960s–1980s [6]. However, there is evidence that HCV transmission is still occurring at high levels [2]. Given the high prevalence of HCV and its distribution among older generations, Egypt unsurprisingly has the highest burden of advanced liver disease from HCV globally [1].

Until recently, first-line therapy for patients chronically infected with genotype 4 HCV was 24 or 48 weeks of peginterferon-alfa in combination with ribavirin. In patients with genotype 4 infection, rates of sustained virological response with peginterferon and ribavirin treatment are generally higher than seen for genotype 1 HCV but lower than for genotypes 2 or 3 HCV [7]. Given the modest success rates, difficulty of administration, and poor tolerability associated with peginterferon and ribavirin, treatment uptake has been low, and the vast majority of patients with HCV in Egypt are untreated [8].

Sofosbuvir, a potent inhibitor of the HCV NS5B polymerase, has recently been approved for the treatment of HCV in Egypt. Sofosbuvir is administered orally once daily and has a high genetic barrier to resistance. In small cohorts of HCV genotype 4 patients, sofosbuvir in combination with peginterferon and ribavirin has resulted in rates of sustained virological response (SVR) of 82% to 96% [9], [10]. Sofosbuvir has a favorable safety profile, and most adverse reactions reported in clinical studies with sofosbuvir have been attributable to concurrent use of peginterferon or ribavirin [11].

A well tolerated, all-oral, interferon-free regimen with a high rate of sustained virological response could have a major impact on the prevalence and incidence of HCV in Egypt. We evaluated the efficacy and safety of 12 or 24 weeks of an all-oral combination of sofosbuvir plus ribavirin in Egyptian patients with HCV genotype 4.