Rizk Hanan H, Hamdy Nadia M, Al-Ansari Nadia L, El-Mesallamy Hala O
Biochemistry Department, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt.
Endemic Medicine Department & Hepatology Unit, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
PLoS One. 2016 Apr 21;11(4):e0153895. doi: 10.1371/journal.pone.0153895. eCollection 2016.
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.
This 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.
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).
IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients.
埃及是难以治疗的慢性丙型肝炎病毒（HCV）4型感染率最高的国家。治疗前因素可指导治疗个体化，这有助于优化治疗，并且白细胞介素IL28B基因多态性已被证明与HCV治疗反应密切相关。编码T细胞反应抑制剂的基因多态性在疾病进展中发挥作用，如程序性细胞死亡蛋白1（PD-1）和细胞毒性T淋巴细胞抗原4（CTLA-4），可能是预测治疗反应的候选标志物。
这项队列研究纳入了200例在2个肝病中心接受聚乙二醇干扰素α-2a和利巴韦林治疗的慢性HCV 4型感染患者。使用TaqMan®基因分型检测法对从每位患者收集的DNA进行IL28B基因区域（rs12979860）、PD1.3（rs11568821）和CTLA-4（rs231775）多态性的基因分型。根据反应情况将患者分为持续病毒学应答者（SVR）或无应答者（NR）。采用多因素逻辑回归分析来确定与治疗反应相关的潜在标志物、宿主治疗前临床和病毒预测因素，包括病毒载量、胰岛素抵抗和甲胎蛋白（AFP）。
我们的结果显示，在多因素分析中，IL28B C/C基因型是SVR的最显著预测因子（OR = 10.86；p<0.0001），其次是AFP（OR = 0.915；p = 0.001），然后是CTLA-4/G基因型（OR = 1.948；p = 0.022）。然而，PD-1.3/A基因型和血小板计数仅在单因素分析中与反应显著相关（分别为OR = 1.973；p = 0.023；OR = 1.007；p = 0.009）。
IL28B单核苷酸多态性、AFP水平和CTLA-4单核苷酸多态性可联合用于预测HCV 4型感染埃及患者的治疗反应。
