Cytomegalovirus and Epstein-Barr virus in concordance with Interleukin-28B polymorphism as a predictor to interferon therapy in hepatitis C patients

Abstract

HCV is a major factor of liver disease and one of the most important health issues worldwide. It has approximately 175 million Global Disease Burden which represent almost 3% of the whole population in the World (Munir et al., 2010). The prevalence of hepatitis C virus (HCV) in Egypt is over 14.7% of adult population. Egypt has the highest prevalence of hepatitis C in the world and consequently a high frequency of hepatocellular carcinoma (HCC) (Guerra et al., 2012). Interferon has been the cornerstone of chronic HCV treatment for the past two decades. Pegylated interferon alpha (PEG-IFN) and ribavirin (RBV) has resulted in sustained virologic response (SVR) of up to 40–50% for genotype 1 and 4 and up to 70–80% in genotype 2 and 3 (Ghany et al., 2009). Genetic analysis of the host may thus predict which patients are more likely to respond to treatment, taking into account that IL- 28B genotype is only one of many factors that can influence response rates to PEG-IFN/RBV therapy in HCV infection (Bellanti et al., 2012). The rs12979860 SNP resides 3 kb upstream of the IL-28B gene, and variations at this position are associated with approximately 2-fold differences in spontaneous clearance and response to treatment. The C/C genotype is associated with Chapter VI: SUMMARY AND CONCLUSION 136 better outcomes, and the T/T genotype, worse outcomes (Pagliaccetti & Robek, 2010). Both host and viral factors are recognized to be important but do not adequately explain the observed variation in response to interferon based therapy for chronic HCV (Domagalski et al., 2013). The search for additional predictive factors for response is mandatory. Co-infection with other pathogens is, in some instances, an interfering factor against host genotype based prediction (El Awady et al., 2013). Epstein-Barr virus (EBV) and Cytomegalovirus (CMV), members of the herpesvirus family, are common viruses that cause infectious mononucleosis (IM) characterized by fever, pharyngitis and lymphadenopathy. EBV/CMV infects at least 90% of the world’s population and can persist in a latent form after primary infection. Reactivation can occur years later, particularly under conditions of immunosuppression (Wang et al., 2010). Regarding co-infection with CMV or EBV in chronic hepatitis C patients, there were many contradictory conclusions about the effect of these co-infection on HCV patients’ outcome. Accordingly, the aim of this study was to explore whether co-infection with CMV and/or EBV could significantly affect the response to IFN on HCV patients and hence could be considered Chapter VI: SUMMARY AND CONCLUSION 137 as significant predictor to interferon therapy in concordance with Interleukin-28B polymorphism. 105 adult Egyptian patients with chronic HCV infection - who received Pegylated interferon alpha and ribavirin (PEGIFN/ RBV) therapy - have been enrolled in this study. According to their response to treatment, they were categorized into two different groups: IFN responder patients (SVR) (n=38), 67 IFN nonresponder patients (NR).