Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt.

OBJECTIVE: We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens. DESIGN: In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12). RESULTS: We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin. CONCLUSION: Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir. TRIAL REGISTRATION NUMBER: NCT02487030.

Innovative strategies for the elimination of viral hepatitis at a national level: A country case series.

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints.

Evidence of sustained reductions in the relative risk of acute hepatitis B and C virus infections, and the increasing burden of hepatitis a virus infection in Egypt: comparison of sentinel acute viral hepatitis surveillance results, 2001-17.

BACKGROUND: Egypt ranks fifth for the burden of viral hepatitis worldwide. As part of Egypt's renewed national strategy for the elimination of viral hepatitis, surveillance for acute viral hepatitis (AVH) was re-established during 2014-2017 to describe the current epidemiology and associated risk factors, and changes from surveillance conducted during 2001-2004. METHODS: Patients with suspected AVH were enrolled, completed a questionnaire, and provided blood for testing for hepatitis viruses A (HAV), B (HBV), C (HCV), D, and E (HEV) infections by enzyme-linked immunosorbent assay. Odds ratios and Chi2 were used to detect differences between hepatitis types by patient characteristics and exposures. Newcombe-Wilson method was used to compare results between surveillance periods 2001-2004 and 2014-2017. RESULTS: Between 2014 and 2017, among 9321 patients enrolled, 8362 (89.7%) had one or more markers of AVH including 7806 (93.4%) HAV, 252 (3.0%) HCV, 238 (2.8%) HBV, and 31 (0.4%) HEV infection. HAV infection occurred most commonly among children < 16 years age, while HBV infection occurred among ages 16-35 years and HCV infection in ages greater than 45 years. Healthcare-associated exposures were significantly associated with HBV and HCV infections compared to HAV infection including receiving therapeutic injections, surgery, wound suture, or urinary catheter and IV line insertions, while significant lifestyle exposures included exposure to blood outside the healthcare system, IV drug use, or incarceration. Exposures significantly associated with HAV infection were attending nursery or pre-school, contact with person attending nursery or pre-school, having meals outside the home, or contact with HAV case. Compared with AVH surveillance during 2001-2004, there was a significant increase in the proportion of HAV infections from 40.2 to 89.7% (RR = 2.3) with corresponding reductions in the proportions of HBV and HCV infections from 30.0 to 2.8% (RR = 0.1) and 29.8 to 3.0% (RR = 0.1), respectively. CONCLUSIONS: Healthcare-associated exposures were significantly association with and remain the greatest risk for HBV and HCV infections in Egypt. Additional studies to evaluate factors associated with the reductions in HBV and HCV infections, and cost effectiveness of routine HAV immunization might help Egypt guide and evaluate control measures.

Pathways to ensure universal and affordable access to hepatitis C treatment.

Direct-acting antivirals (DAAs) have dramatically changed the landscape of hepatitis C treatment and prevention. The World Health Organization has called for the elimination of hepatitis C as a public health threat by 2030. However, the discrepancy in DAA prices across low-, middle- and high-income countries is considerable, ranging from less than US$ 100 to approximately US$ 40,000 per course, thus representing a major barrier for the scale-up of treatment and elimination. This article describes DAA pricing and pathways to accessing affordable treatment, providing case studies from Australia, Egypt and Portugal. Pathways to accessing DAAs include developing comprehensive viral hepatitis plans to facilitate price negotiations, voluntary and compulsory licenses, patent opposition, joint procurement, and personal importation schemes. While multiple factors influence the price of DAAs, a key driver is a country's capacity and willingness to negotiate with pharmaceutical companies. If negotiations do not lead to a reasonable price, governments have the option to utilise flexibilities outlined in the Agreement on Trade-Related Aspects of Intellectual Property Rights. Affordable access to DAAs is underpinned by collaboration between government, civil society, global organisations and pharmaceutical companies to ensure that all patients can access treatment. Promoting these pathways is critical for influencing policy, improving access to affordable DAAs and achieving hepatitis C elimination.

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.