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白细胞介素28B基因多态性与4型慢性丙型肝炎埃及患者接受索磷布韦加达卡他韦治疗后的持续病毒学应答之间的关联

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients.

作者信息

Hassanien Khalid S, El-Sayed El-Sayed M, Ismail Raed S, Zakarya Zakarya M, Helal Gouda K

机构信息

Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

出版信息

J Clin Pharm Ther. 2021 Aug;46(4):942-949. doi: 10.1111/jcpt.13417. Epub 2021 Mar 25.

Abstract

WHAT IS KNOWN AND OBJECTIVE

Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan-genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first-in-class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV-4.

METHODS

Samples were collected at week zero. One hundred and thirty-one patients who reached the end of treatment (at week 12) were divided into three groups, according to their interleukin 28B genotype: Group A included 31 patients (CC genotype), group B included 79 patients (CT genotype) and group C had 21 patients (TT genotype). All patients received treatment for 3 months in the form of sofosbuvir plus daclatasvir with ribavirin (in case of cirrhotic patients) or without ribavirin (in case of non-cirrhotic patients).

RESULTS AND DISCUSSION

Sustained virological response rate was significantly higher in patients with IL28B (CC genotype) vs. (non-CC genotype) (100 vs.88%) (p < 0.0001).These patients also showed lower rates of post-treatment relapse and non-response, compared with the CT and TT patients (0% vs. (7.59% and 28.5%, respectively) (p < 0.0001). Also, patients with CC genotype showed higher sustained virological response than non-CC genotypes on both cirrhotic (100% vs. 68.75%) and non-cirrhotic patients (100% vs. 91.66%) (p ≤ 0.0001).

WHAT IS NEW AND CONCLUSION

Our results suggest that IL28B genotype contributes to the prediction of response to sofosbuvir plus daclatasvir.

摘要

已知信息与研究目的

索磷布韦已获批成为首个对丙型肝炎病毒(HCV)具有泛基因型活性的非结构蛋白5B聚合酶抑制剂。达卡他韦是一流的丙型肝炎病毒非结构蛋白5A复制复合体抑制剂。我们旨在评估白细胞介素28B(IL28B)参考单核苷酸多态性(rs12979860,CC基因型)对预测感染HCV-4的埃及患者接受索磷布韦加达卡他韦治疗后的持续病毒学应答的有效性。

方法

在第0周采集样本。131例治疗结束(第12周)的患者根据其白细胞介素28B基因型分为三组:A组包括31例患者(CC基因型),B组包括79例患者(CT基因型),C组有21例患者(TT基因型)。所有患者接受为期3个月的索磷布韦加达卡他韦治疗,肝硬化患者联合利巴韦林,非肝硬化患者不联合利巴韦林。

结果与讨论

IL28B(CC基因型)患者的持续病毒学应答率显著高于非CC基因型患者(100%对88%)(p<0.0001)。与CT和TT基因型患者相比,这些患者治疗后复发和无应答率也更低(分别为0%对7.59%和28.5%)(p<0.0001)。此外,CC基因型患者在肝硬化患者(100%对68.75%)和非肝硬化患者(100%对91.66%)中的持续病毒学应答均高于非CC基因型患者(p≤0.0001)。

新发现与结论

我们的结果表明,IL28B基因型有助于预测索磷布韦加达卡他韦的治疗应答。

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