الفهرس 
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Abstract
About 170 million people worldwide suffer from chronic infection with the hepatitis C virus (HCV), HCV is one of the main causes of chronic liver disease worldwide. Egypt has the highest prevalence of adult HCV infection in the world, with > 90% of cases having HCV genotype 4.
Treatment of HCV using combination of pegylated interferon (PEG-IFN) plus ribavirin fails in about 45% of the patients and is physically and economically demanding. Many viral and host factors have been investigated as predictors for achieving viral clearance.Differences in host genetics are believed to influence the outcome of HCV infection. The interleukin28B (IL28B) variability has a strong impact on the response to the HCV treatment.
The aim of the present study was to assess the effect of two different IL28B polymorphisms (rs12979860 and rs8099917) on the response to the pegylated-interferon (Peg-IFN)/Ribavirin treatment in the Egyptian hepatitis C virus genotype 4 patients.
The present study was carried on 50 apparently healthy controlsubjects as well as 66 HCV-G4 infected Egyptian patients, thirty six showed response while 30 patients showed no response to the treatment.
Methods:
• All patients and controls were subjected to:
Full medical history and clinical examination
Full biochemical investigation
Molecular genetic investigations
• While only patients were subjected to:
Virological investigations
Histological investigations
• The molecular genetic investigations included:
I. Detection of HCV RNA using Real Time PCR for the virological investigation of the patients.
II. Genotyping of single nucleotide polymorphisms (SNPs) of the IL28B rs12979860 and rs8099917 were carried out using the TaqMan® Allelic Discrimination assay method on Applied Biosystems real time PCR for both the patients and control.
The results of this study were as the following:
• The virological response at week 12, 42 of 66 (63.63%) patients reached Early Virological Response (EVR), while 10 of these 42 (23.81%) patients had breakthrough. At week 24, 36 of 66 patients had undetectable HCV RNA and only 4 (11.11%) patients of the 36 patients showed Delayed Virological Response (DVR).
• Comparing the baseline biochemical, histological and virological investigation between responders and non-responders , Liver fibrosis stage is the only parameter that showed a statistically significant difference (p =0.02).
• The genotype distribution patterns of single nucleotide polymorphisms (rs12979860 and rs8099917) of IL28B gene among the healthy control group and the HCV including the responders and non-responders subgroups showed:
IL28 rs12979860 genotypes’ distribution patterns’ showed that CT genotype had higher frequency than CC and TT genotypes among the healthy control group (54%, 40%, 6%) and the patients (62.12%, 25.76%, 12.12%), The two subgroups of responders and non-responders showed the same results with frequencies (55.56%, 41.67%,2.78%) and (70%, 6.67%, 23.33%), respectively.
IL28 rs8099917 genotypes’ distribution patterns’ showed that TT genotype had higher frequency than GT and GG genotypes among the healthy control group (54%, 44%, 2%) and the patients (59.09%, 36.36%,4.55%)The two subgroups of responders and non-responders showed the same results with frequencies (66.67%, 30.56%, 2.78%)and (50%, 43.33%, 6.67%), respectively.
The response to the treatment was significantly associated with CC alleles of rs12979860p= 0.00055 (OR, 10; 95% CI 2.06-48.56) While the TT genotype was significantly associated with the non-respond to the treatment p = 0.018 (OR, 0.094; 95% CI 0.0108-0.81).
The TT genotype of IL28B SNP rs8099917 was more frequent genotype among the responders group than the non-responders group but it didn’t reach the statistically significant difference value p>0.05 . This showed that there is no significant association between all rs8099917 genotypes and the response to the treatment.
There was statistically significant difference between the number of C alleles and the response to the treatment(p value = 0.00129). This showed that carrying at least one copy of the C allele (genotypes CT and CC) had approximately 3 times the odds of response compared to those with genotype TT (OR, 3.1818; 95% CI 2.447- 4.137).
Results showed significantly association between the combination of the CC genotype in patients with liver fibrosis stage less than 2 (F<2) and the response to the treatment (p = 0.0297).