Although triple therapy Volasertib BI 6727 with IFN + Rb and boceprevir or telaprevir has produced a sustained virologic response (SVR) of approximately 70%, this regimen still requires co-administration of IFN + Rb and has a high cost in most countries. At present, only 50% of patients infected with HCV genotype 1 achieved an SVR, defined as absence of HCV RNA six months after the cessation of therapy[8,9]. Even in non-genotype 1 patients, who are reported to have better responses to the combination treatment, the SVR rate was about 75%[10,11]. A number of viral and host factors may reduce adherence to the treatment. In addition to a limited treatment response to current combined therapy by some patients, treatment is often poorly tolerated due to various adverse reactions, including flu-like symptoms, severe fatigue, and neutropenia.
Moreover, the inconvenience of a prolonged course of weekly injections of pegylated interferon and the high costs of the antiviral drugs make some patients give up the combined therapy. Additional research to advance HCV treatment regimens is needed to increase the patient adherence and response to therapy, thereby increasing SVR rates. It is also puzzling why approximately 30% of patients with acute HCV infection experience spontaneous viral clearance, whereas the rest become chronically infected[2,3]. Meanwhile, the global epidemiology of HCV infection shows that the different HCV genotypes clearly show geographic variation in their relative frequencies. Genotype 1, consisting of subtypes 1a and 1b, is the most prevalent genotype worldwide, with a higher prevalence of 1b in Europe and 1a in the United States[11-13].
The estimated prevalence of people with detectable anti-HCV antibodies is highest in Africa, with an overall seroprevalence of 5.3%, and most common in genotype 4. In contrast, the infection rate of HCV is lower, and genotype 2 or 3 are more frequent in Asia[11-13]. Furthermore, previous studies have revealed that the effectiveness of the combination treatment Cilengitide with peg-interferon and ribavirin differs among various ethnic populations. In the US, chronic HCV patients of European ancestry have a higher probability of being cured than patients of African ancestry. It is well documented that patients originating from East Asia are more likely to achieve SVR than patients from Europe. These observations suggest that host genetic variations play a critical role in patients infected with HCV. Four recent genome-wide association studies (GWAS) independently identified several single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) locus. Variability at that locus is known to be associated with the successful treatment of HCV infection[15,17-19].