Hepatitis C virus genotype 4 therapy: progress and challenges

Abstract

The hepatitis C virus genotype 4 (HCV‐4) is prevalent in Egypt, the Middle East and Africa. Recently, the epidemiology of HCV‐4 has changed and this genotype has begun to cross borders and spread to several regions in Europe through immigration and injection drug use. HCV‐4 has been considered a difficult‐to‐treat genotype based on the low sustained virological response (SVR) rates obtained with conventional interferon (IFN)‐based regimens. Pegylated interferons (PEG‐IFN) plus ribavirin therapy for chronic HCV‐4 has been associated with increased SVR rates of more than 60%. Shorter treatment of chronic HCV‐4 patients with rapid and early virological responses has been associated with high SVR rates, better compliance, fewer adverse events and lower costs. Despite this progress, the treatment of HCV‐4 non‐responders, injection drug users, patients coinfected with human immunodeficiency virus, thalassaemic patients, patients on haemodialysis and patients with HCV‐4 recurrence after liver transplantation still represents a significant therapeutic challenge. Treatment of HCV‐4 has markedly improved, with higher sustained response rates and the possibility of shorter regimens. Despite the recent progress in the treatment of HCV‐4, more research is required to optimize current therapy and include genotype 4 patients in clinical trials on emerging therapies such as specifically targeted antiviral therapy for HCV with protease and/or polymerase inhibitors.

Evidence-based clinical guidelines for immigrants and refugees

“…278,[288][289][290]295,296 For other genotypes (4,5,6,7,8), the results are less well defined: they appear to be better than for genotype 1 but not as good as for genotypes 2 and 3. 297,298 The treatment is associated with numerous adverse effects, and 10% to 14% of patients discontinue therapy because of an adverse event, most commonly psychiatric symptoms or severe anemia. 278,299 Persons with advanced cirrhosis are less likely to have a response to treatment, which highlights the importance of initiating treatment before advanced liver disease develops.…”

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

“…The main cause of chronic HCV in the Middle East and Egypt is HCV genotype 4 (HCV-4). Recently, HCV infection has been reported in southern Europe among immigrants, mostly from Africa, and among intravenous drug users 1,2 .…”

Efficacy of daclatasvir plus peginterferon alfa and ribavirin for patients with chronic hepatitis C genotype 4 infection

“…Seven genotypes of HCV have been identified. Of them, genotype 1 is the most prevalent infection worldwide (Smith et al, 2014), while genotype 4 accounts for 20% of the global burden of HCV infection, with a high prevalence in the Middle East and Central and North Africa (Cornberg et al, 2011;Kamal, 2011). Multiple factors affect patients' response to antiviral therapy including viral genotype, viral load, host genetics, and patients' demographics (Ghany et al, 2009;Thompson et al, 2010).…”