AMINO ACID SUBSTITUTION IN HEPATITIES C VIRUS CORE AND GENETIC VARIATION IN INTERLEUKIN 28BGENE AND THEIR CORRELATION TO INTERFERON TREATMENT FAILURE IN CHRONIC HCV EGYPTIAN PATIENTS

Abstract

Hepatitis C virus (HCV) is a disease with significant global impact. According to the World Health Organization there are 170 - 200 million people chronically infected with the HCV, corresponding to 2 – 2.5% of the world’s total population. Egypt has the highest prevalence of HCV in the world (14.7%).

The standard of care for patients with chronic hepatitis C is pegylated interferon alpha (peg-IFN-a) in combination with ribavirin (RBV).The most serious problem facing these patients is the resistance to PEG-IFN plus ribavirin therapy. This resistance is related to genetic polymorphism in different patients which explain the different response of individuals to the IFN/RBVtherapy.A positive response to treatment is defined as a sustained virological response (SVR; a negative hepatitis C PCR test 3 months after cessation of therapy). The SVR rate for individuals infected with HCV genotypes 1 or 4 ranges between 40 and 50% and requires 12 months of therapy.

For this reason, we planned to study genetic polymorphism which interfere with the response to IFN/RBV in HCV genotype 4 Egyptian patients.

Genome-wide association studies identified single nucleotide polymorphisms (SNP) in the IL28B region associated with sustained virologic response (SVR) to peginterferon/ribavirin combination therapy of chronic hepatitis C. These SNPs span the region that encodes three cytokine genes belonging to the interferon. IL28B had two SNP on chromosome 19, rs8099917 and rs12979860.