Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Abstract

Background: IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance. Objectives: In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined. Patients and Methods: Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals. Results: A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Data Mining and Machine Learning Algorithms Using <i>IL28B</i> Genotype and Biochemical Markers Best Predicted Advanced Liver Fibrosis in Chronic Hepatitis C

“…The results of this study revealed IL28B rs12979860 C T genotype as the commonest genotype (68.9 ) and is in agreement with previous studies done on Egyptian patients (19,(30)(31)(32), suggesting a possible role of this genotype in the transition of a normal hepatocyte into an abnormal one. This genotype distribution was suggested to be a consequence of environmental or ethnic variation (30,32).…”

“…The frequency of CC genotype in our samples was smaller than all those mentioned above. This may be explained by the results obtained by El-Awady et al that showed a sharp decline in the C C genotype along the progression of chronic HCV infection towards the end-stage liver disease (31), and the majority of our patients had advanced fibrosis stages (F3-F4) When applying our REPTree, IL28B genotype was chosen as the most decisive variable, occupying the root node, to predict advanced fibrosis stages. IL28B gene plays a role in the outcome of chronic hepatitis C (30).…”

IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCV

“…One of these SNPs is rs12979860 C/T, it is pivotal in predicting the outcome of HCV infections (Thomas et al, 2009). In El-Awady et al (2012), it was demonestrated that genotype C/C is significantly associated with viral clearance during the acute stage of HCV infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in end stage liver disease, which were reported in this study, indicated a pivotal role of this genotype against disease progression in HCV infected patients.…”

Association of the interleukin-28B gene polymorphism with development of hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta-analysis

“…After our selection, 7 casecontrol studies including 1152 HCC and/or LC cases and 1326 controls fulfilled the inclusion criteria (Barreiro et al, 2011;Fabris et al, 2011;Falleti et al, 2011;Agundez et al, 2012;El-Awady et al, 2012;Eurich et al, 2012;Ren et al, 2012). The quality of the studies was considered acceptable for our meta-analysis.…”

“…There were 5 case-control studies Agundez et al, 2012;El-Awady et al, 2012;Eurich et al, 2012;Ren et al, 2012), which had been performed to study the rs12979860 poly morphism and HCC risk. The results of the meta-analysis are shown in Table 3.…”