الفهرس 
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Abstract
Chronic hepatitis C infection remains a global public health concern. It has been well documented that Egypt has the highest prevalence rates of HCV infection in the world. chronic hepatitis C infection is a major cause of cirrhosis and hepatocellular carcinoma.
The standard treatment strategy for HCV infection is combined pegylated interferon and ribavirin. Treatment aims to achieve SVR defined as the persistent absence of detectable HCV RNA in serum of patients 6 months or more after completing antiviral treatment and to prevent further complications. However, adverse effects are common with this combination therapy.
Interferon λ-3 known as interleukin 28-B (IL28-B) has been shown to have antiviral properties. A single-nucleotide polymorphism (SNP) upstream of IL 28-B gene was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with peg-IFN/RBV.
The aim of this study was to investigate the association between SNP (rs8099917) of the IL28B gene and early virological response in chronic hepatitis C Egyptian patients.
The study was carried on 124 Egyptian subjects of matched age and sex . They were divided into 25 apparently healthy control subjects and 99 patients: 49 responders and 50 non-responders to peg-IFN/RBV therapy according to their early virological response.
To all subjects fasting plasma samples were analyzed for glucose, creatinine, albumin, total bilirubin as well as activities of aminotransferases, alkaline phosphatase and gamma glutamyl transferase. Genomic DNA was extracted from peripheral blood leukocytes of all subjects using ion-exchange column chromatography. Genotyping of rs 8099917 SNP of interleukin 28-B gene was carried out by an allelic discrimination real-time polymerase chain reaction using dual labeled fluorogenic TaqMan probes SNP genotyping technology.
Results of the present study revealed that the genotype distribution pattern of rs8099917 SNP among non-responders group was statistically significantly different from that of the responders group where the non-responders group had a higher frequency of both the homo-mutant genotype “GG” and the hetero-mutant genotype “TG” and a lower frequency of the homo-wild genotype “TT” than the responders group. Both patterns were in agreement with those expected under the Hardy-Weinberg equilibrium assumption. The present study also found that CHC patients having hetero-mutant genotype TG or the homo-mutant genotype “GG”, were both at a significantly higher risk of non-response to peg-IFN/RBV therapy than CHC patients having homo-wild TT genotype. The non-responders group had a statistically significant higher frequency of the mutant allele “G” than responders group. This was associated with a statistically significant increased risk of non-response to peg-IFN/RBV therapy.
Furthermore, non-responders group had a statistically significant higher level of AST, ALT and GGT when compared to the corresponding values among responders group. There was a positive association between GGT and genotype. Also there was a positive association between AST, ALT, GGT, degree of liver fibrosis and non-response to treatment. However, there was no association between degree of fibrosis and genotype in the subgroup of patients having liver biopsy.
In conclusion: the present work demonstrated an inverse association between the minor allele (G) of the rs8099917 SNP of IL28B and EVR to peg-IFN/RBV treatment among the studied Egyptian CHC patients. Furthermore only GGT and genotype were independent predictors of response to treatment.