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丙型肝炎患者中爱泼斯坦-巴尔病毒和白细胞介素-28B基因多态性对干扰素治疗反应的预测作用

Epstein-Barr virus and Interleukin-28B polymorphism in the prediction of response to interferon therapy in hepatitis C patients.

作者信息

Zekri Abdel-Rahman N, Abdullah Dina, Osman Ahmed, El-Rouby Mahmoud N, Zayed Naglaa, Esmat Gamal, Elakel Wafaa, Hafez Hanan Abdel

机构信息

Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Arab J Gastroenterol. 2015 Sep-Dec;16(3-4):84-9. doi: 10.1016/j.ajg.2015.09.013. Epub 2015 Oct 31.

DOI:10.1016/j.ajg.2015.09.013
PMID:26526510
Abstract

BACKGROUND AND STUDY AIMS

In chronic hepatitis C virus (HCV), viral and host factors are known to be predictors for anti-viral therapy. IL-28B genotype strongly influences treatment outcome, while Epstein-Barr virus (EBV) co-infection could accelerate the course of chronic HCV infection. This study was conducted to assess whether EBV co-infection adds to the predictive value of IL-28B.

PATIENTS AND METHODS

A total of 105 patients with chronic HCV were classified according to their response to treatment into two groups: 38 sustained virological responders (SVRs) and 67 nonresponders (NRs). Collected sera at baseline and follow-up (FUP) were used for assessing EBV antibodies by enzyme-linked immunosorbent assay (ELISA) and the expression of EBV genes (BNLF-1, BZLF-1, and EBER-2) by polymerase chain reaction (PCR). Collected peripheral blood was used for detecting IL-28B rs.12979860 single-nucleotide polymorphism.

RESULTS

Regarding IL-28B genotype frequencies, a significant difference (p=0.003) was observed between SVRs (C/C=51.4%, C/T=48.6%, T/T=0%) and NRs (C/C=25%, C/T=55%, T/T=20%). On assessing EBV infection at baseline and FUP, it was found that 61% and 55% were positive, respectively, with no significant difference between SVRs and NRs. As for anti-viral capsid antigen (VCA) antibodies, the NRs had significantly higher baseline anti-VCA immunoglobulin M (IgM) levels than SVRs (p=0.01). While FUP anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG reported a significant decline within SVR patients (p=0.02), neither baseline nor FUP anti-VCA IgG levels showed a statistically significant viral response. Finally, on comparing EBV markers with CC versus CT and TT genotypes, it was found that FUP anti-VCA IgG levels were significantly increased in CC genotype (p=0.003).

CONCLUSION

Interleukin-28B polymorphism could be a possible predictor of response to pegylated interferon/ribavirin therapy (PEG-IFN/RBV). Furthermore, co-infection with EBV did not affect the response to IFN-based therapy in HCV-infected patients.

摘要

背景与研究目的

在慢性丙型肝炎病毒(HCV)感染中,病毒和宿主因素是抗病毒治疗的预测指标。白细胞介素-28B(IL-28B)基因型强烈影响治疗结果,而爱泼斯坦-巴尔病毒(EBV)合并感染可能加速慢性HCV感染进程。本研究旨在评估EBV合并感染是否会增加IL-28B的预测价值。

患者与方法

105例慢性HCV患者根据治疗反应分为两组:38例持续病毒学应答者(SVR)和67例无应答者(NR)。在基线和随访(FUP)时采集的血清用于通过酶联免疫吸附测定(ELISA)评估EBV抗体,并通过聚合酶链反应(PCR)评估EBV基因(BNLF-1、BZLF-1和EBER-2)的表达。采集的外周血用于检测IL-28B rs.12979860单核苷酸多态性。

结果

关于IL-28B基因型频率,SVR组(C/C = 51.4%,C/T = 48.6%,T/T = 0%)和NR组(C/C = 25%,C/T = 55%,T/T = 20%)之间观察到显著差异(p = 0.003)。在评估基线和FUP时的EBV感染情况时,发现分别有61%和55%呈阳性,SVR组和NR组之间无显著差异。至于抗病毒衣壳抗原(VCA)抗体,NR组的基线抗VCA免疫球蛋白M(IgM)水平显著高于SVR组(p = 0.01)。虽然SVR患者中FUP抗爱泼斯坦-巴尔核抗原-1(EBNA-1)IgG报告有显著下降(p = 0.02),但基线和FUP抗VCA IgG水平均未显示出统计学上显著的病毒应答。最后,在比较EBV标志物与CC、CT和TT基因型时,发现CC基因型的FUP抗VCA IgG水平显著升高(p = 0.003)。

结论

白细胞介素-28B多态性可能是聚乙二醇化干扰素/利巴韦林治疗(PEG-IFN/RBV)反应的一个可能预测指标。此外,EBV合并感染并不影响HCV感染患者对基于干扰素治疗的反应。

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