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Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4.

ABSTRACT: BACKGROUND:Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response. METHODS:This cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN ?-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response. RESULTS:Our results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively). CONCLUSION:IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients.

SUBMITTER: Rizk HH

PROVIDER: S-EPMC4839712 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4.

Rizk Hanan H HH Hamdy Nadia M NM Al-Ansari Nadia L NL El-Mesallamy Hala O HO

PloS one 20160421 4

<h4>Background</h4>Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA ...[more]

PMID: 27100663

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Project description:BackgroundIL28B 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.ObjectivesIn 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 methodsFrequencies 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.ResultsA 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.ConclusionsGenotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.

Dataset Information

Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4.

Publications

Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4.

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