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准种之间的遗传距离和异质性是埃及丙型肝炎病毒4型患者对干扰素反应的关键预测指标。

Genetic distance and heterogenecity between quasispecies is a critical predictor to IFN response in Egyptian patients with HCV genotype-4.

作者信息

Zekri Abdel Rahman N, El-Din Hanaa M Alam, Bahnassy Abeer A, Khaled Mohsen M, Omar Ashraf, Fouad Inas, El-Hefnewi Mahmoud, Thakeb Fouad, El-Awady Mostafa

机构信息

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

出版信息

Virol J. 2007 Feb 14;4:16. doi: 10.1186/1743-422X-4-16.

Abstract

BACKGROUND

HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype 4 is the most common genotype of HCV and its response to treatment is still a controversy.

METHODS

HCV genotype 4 quasispecies diversity within the 5' untranslated region (5'UTR) was studied in a series of 22 native Egyptian patients with chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7 control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC genotyping kit.

RESULTS

At the 48th week of treatment, 15 patients (68%) showed virological response. Whereas HCV-RNA was still detected in 7 patients (32%) in this period; of those, 6 experienced a partial virological response followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical response. The four females included in this study were all responders. There was a significant correlation between the response rate and lower fibrosis (p = 0.026) as well as the total number of mutation spots (including all the insertions, deletions, transitions and transversions) (p = 0.007, p = 0.035).

CONCLUSION

Patients who responded to interferon treatment had statistically significant less number in both transitions (p = 0.007) and the genetic distances between the quasispecies (p = 0.035). So, viral genetic complexity and variability may play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among non responders who need further study to confirm this observation.

摘要

背景

丙型肝炎病毒(HCV)是埃及主要的健康问题之一,在该国高度流行。4型基因型是HCV最常见的基因型,其对治疗的反应仍存在争议。

方法

对22例未接受过治疗的埃及慢性丙型肝炎病毒本土患者进行了研究,这些患者符合美国国立卫生研究院(NIH)关于聚乙二醇化干扰素和利巴韦林联合治疗的所有标准,并研究了其5'非翻译区(5'UTR)内HCV 4型准种多样性,且将其与治疗结果相关联。该研究还纳入了7例未接受抗病毒治疗的对照患者。使用TRUGENE HCV 5-NC基因分型试剂盒进行HCV测序。

结果

治疗第48周时,15例患者(68%)显示出病毒学应答。而在此期间仍有7例患者(32%)检测到HCV-RNA;其中,6例经历了部分病毒学应答,随后在治疗期间出现病毒突破。只有1例患者未显示任何病毒学或生化应答。本研究纳入的4名女性均为应答者。应答率与较低的纤维化程度(p = 0.026)以及突变位点总数(包括所有插入、缺失、转换和颠换)之间存在显著相关性(p = 0.007,p = 0.035)。

结论

对干扰素治疗有应答的患者在转换(p = 0.007)和准种之间的遗传距离(p = 0.035)方面在统计学上显著较少。因此,病毒遗传复杂性和变异性可能在对干扰素治疗的应答中起作用。所有三组的一致性比对在三组之间未显示出特征性模式。然而,在无应答者中观察到160位点的G到A转换,这需要进一步研究来证实这一观察结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2abc/1805740/55481ec92d38/1743-422X-4-16-1.jpg

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