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

Abstract

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.

Interleukin-28B Polymorphism is a Pharmacogenetic Predictor during Sofosbuvir Plus Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C Egyptian Patients

“…Moreover, high expression of IFN-λ has been recorded in patients with rs12979860 CC variant [29]. Recently, IL28B SNP, alpha fetoprotein level, and cytotoxic T-Lymphocytes antigen-4 (CTLA-4) SNP could be used in conjunction to predict treatment response in HCV-G4 infected Egyptian patients [30]. In addition, Esmail et al [31] demonstrated that IL-28B SNP polymorphism is considered as a vital predictor of viral relapse.…”

Detection of HCV genotypes 1b and 2a by a reverse transcription loop‐mediated isothermal amplification assay

“…Firstly, the HCV pandemic is a major public health concern, especially in China. Additionally, the correlation between different HCV genotype infections and progression of liver diseases is well documented . Secondly, since nucleic acid‐based detection techniques such as reverse transcriptase PCR and real‐time PCR are time‐consuming, labor‐intensive, and need skilled personnel and sophisticated equipment, these working conditions limit their extensive application in resource‐limited or point‐of‐care settings.…”

“…Additionally, the correlation between different HCV genotype infections and progression of liver diseases is well documented. [43][44][45] Secondly, since nucleic acid-based detection techniques such as reverse equipment such as an electrophoresis apparatus or UV illuminator; and (iv) the positive color change could last longer without freezing, which allows the storage of the tubes for recording purposes.…”

The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4

“…Several host and viral factors have been investigated to be used as markers to predict the response of chronic hepatitis C patients to the combined IFN and RBV treatment. Viral load was evaluated as a predictive factor by some studies with controversial results8–10 . The stage of liver fibrosis was claimed to be a good predictor of treatment response in HCV infection9,11.…”