BackgroundEgypt 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.MethodsThis cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-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.ResultsOur 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).ConclusionIL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients.

BackgroundImproving prediction of treatment outcomes in chronic hepatitis C (CHC) genotype 4 (G4) is necessary to increase sustained viral response (SVR) rates. Vitamin D related and interferon stimulated genes are good candidates as they are recently crosstalk altering interferon response. Thus single nucleotide polymorphisms (SNPs) within some of these genes and multiple stepwise regression analysis including other independent predictors (IL28B(rs12979860), serum 25OH-vitamin D, serum alfa-fetoprotein (AFP)) were performed on a cohort of 200 Egyptian CHC patients treated with Pegylated interferon-alpha (Peg-IFN) plus ribavirin.MethodsSNPs in cytochrome P-450 (CYP2R1)(rs10741657AG), vitamin D receptor (VDR)(rs2228570AG, rs1544410CT), oligoadenylate synthetases-like (OASL)(rs1169279CT) and adenosine deaminases acting on RNA (ADAR)(rs1127309TC) genes were analyzed by real-time PCR.ResultsThe carrier state of A allele in VDR rs2228570 and CYP2R1 rs10741657 genes were independently associated with SVR [OR 6.453 & 3.536, p < 0.01 respectively]. Combining carriers of A allele in CYP2R1 and VDR genes with IL28B C/C genotype increased the probability of SVR from 80 % to reach 87.8 %, 93 % and 100 %. No relation was found between VDR rs1544410CT, ADAR rs1127309TC, OASL rs1169279CT polymorphisms and treatment outcome. Combining VDR rs2228570 A/A genotype with IL28B C/C genotype increased the probability of SVR from 82 % to reach 100 % and from 29 % to reach 80 % in C/T+ T/T IL28B genotype in none F4 liver disease patients.ConclusionVitamin D related (VDR rs2228570 and CYP2R1 rs10741657) and IL28B rs12979860 genes polymorphisms accurately assure SVR in naïve CHC G4 patients treated with low cost standard therapy.