The relationship between IL-28B genotypes and viral load in HCV chronic hepatitis genotype 4 Egyptian

Abstract

Hepatitis C continues to be a major public health problem affecting approximately 3% of the global population (World Health Organization, 2007) According to the World Health Organization, an estimated 170 million people have chronic hepatitis C (World Health Organization, 2007) estimated HCV prevalence in Egypt range from 11% to 14% with 8 to 10 million having anti-HCV and 5 to 7 million having active infections. HCV prevalence is directly associated with the amount of intravenous tartar emetic used to control schistosomiasis (Mohamed, 2004), 10% -20% of those who are chronically infected with chronic hepatitis C will progress to cirrhosis and 5% will develop hepatocellular carcinoma, by which it has became a worldwide concern to find several ways in early detection and treating such dangerous leathal disease. Several studies were done to search for new treatment agents and combinations such as triple therapy approaches including direct-acting antiviral agents in combination with pegylated interferon α and ribavirin that will enrich treatment response for patients with chronic hepatitis C. Approval of the NS3-4A inhibitors telaprevir and boceprevir in the very near future will give a chance of eradicating HCV in a majority of treated HCV genotype 1 patients (Tellinghuisen et al., 2005).. Nucleoside analogue NS5B inhibitors (Gane et al., 2010), NS5A inhibitors and agents targeting host proteins such as Debio-025 are highly promising for patients infected with other HCV genotypes. However, additional side effects and costs demand intensive efforts to clearly define patients who require triple treatment or not, and to define optimal treatment schedules for individualized durations of therapy. Also new predictors of antiviral response rates are being studied one of them is the single nucleotide polymorphism (rs12979860) upstream of the IL28B gene that was shown to be associate with more than a 2-fold difference in response to HCV drug treatment. Detection of such gene was affordable in the presence of sequencing technologies of the human genome, the region containing rs12979860 and rs8099917 encodes three cytokine genes (IL28A, IL28B, and IL29) belonging to the interferon IFN-k (type-III IFN) family. IFN-k1 and IFN-k2 block HCV replication in human hepatocytic cell lines (Zhu et al., 2005). So the current study aimed to find out whether there is a relation between viral load and IL-28B genotypes before starting treatment in Egyptian patients infected by HCV genotype 4. 30 patients with age ranging between 20 and 60 years from both genders with chronic hepatitis C who will receive pegylated interferon and ribavirin therapy in outpatient clinic of Ain Shams Hospital. All patients were subjected to Medical history, complete blood count, liver profile, serum kidney function tests, viral hepatitis markers, Quantitative HCV PCR before treatment and HCV genotype. And IL28b genotyping by sequencing mechanism to detect type of IL28b polymorphism and patients divided according to their genotype into 3 groups: Group 1: CC Group 2: CT Group 3: TT. Three patients dropped out of study shortly after enrolment in the process of DNA extraction and sequencing due to heamolysed and bad DNA quality of their blood sample taken. So the final number of included patients was 27 patients 21(77.78%) of them were males and 6 were females (22.2 %) the frequencies of the IL-28B genotypes were as follows: CC, 40.74%; CT, 22.22%; and TT, 37.04%. In the present work, there is significant increase of virus load in TT polymorphism group (367.02±308.99) when compared to CT (111.27±87.10) or CC (273.47±311.59) groups. our data showed significant relationship between baseline viral load and IL-28B genotypes and this could serve as a predictor of response to HCV treatment in Egyptian patients infected by HCV genotype 4. In conclusion, baseline viral load is strongly correlated with and IL-28B genotypes.