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欧洲地区1型基因型丙肝病毒患者中NS3多态性Q80K的流行情况。

Prevalence of the hepatitis C virus NS3 polymorphism Q80K in genotype 1 patients in the European region.

作者信息

Sarrazin Christoph, Lathouwers Erkki, Peeters Monika, Daems Bjorn, Buelens Annemie, Witek James, Wyckmans Yves, Fevery Bart, Verbinnen Thierry, Ghys Anne, Schlag Michael, Baldini Alessandra, De Meyer Sandra, Lenz Oliver

机构信息

Johann Wolfgang Goethe University Hospital, Medical Department 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.

出版信息

Antiviral Res. 2015 Apr;116:10-6. doi: 10.1016/j.antiviral.2015.01.003. Epub 2015 Jan 19.

Abstract

Hepatitis C virus (HCV) NS3 polymorphism Q80K is mainly found in patients with HCV genotype (G) 1a, and has been associated with a reduced treatment response to simeprevir with pegylated interferon (P) and ribavirin (R). Prevalence of Q80K among G1 patients may vary geographically. Q80K prevalence in the North-American G1 population in a recent study was 34%. We conducted a post hoc meta-analysis of Q80K polymorphism prevalence among HCV G1-infected patients enrolled in simeprevir and telaprevir Phase II/III studies. Baseline HCV NS3/4A protease sequences were analysed by population sequencing to determine Q80K prevalence. Overall, of 3349 patients from 25 countries in the European region analysed, 35.8%, 63.8% and 0.3% of patients had G1a, G1b and other/unknown HCV G1 subtypes, respectively. Q80K was detected at baseline in 7.5% of HCV G1 patients overall. Examination by subtype showed that 19.8%, 0.5% and 18.2% of patients with G1a, G1b and other/unknown HCV G1 subtypes had the Q80K polymorphism, respectively. Among countries in the European region with sequencing data available for either ⩾20 patients with G1a and/or ⩾40 G1 patients overall, the Q80K prevalence in G1 ranged from 0% in Bulgaria to 18.2% in the UK. Q80K prevalence also varied within G1a across different countries. HCV subtype 1a was correctly determined in 99% of patients by the LiPA v2 assay. A low overall prevalence of Q80K was observed in HCV G1-infected patients in the European region, compared with North America. However, the prevalence varied by country, due to differing ratios of G1a/G1b and differing Q80K prevalence within the G1a populations.

摘要

丙型肝炎病毒(HCV)NS3多态性Q80K主要见于HCV基因1a型(G1a)患者,并且与使用simeprevir联合聚乙二醇化干扰素(P)和利巴韦林(R)治疗反应降低有关。G1患者中Q80K的流行率可能因地域而异。在最近一项研究中,北美G1人群中Q80K的流行率为34%。我们对参与simeprevir和telaprevir II/III期研究的HCV G1感染患者中Q80K多态性流行率进行了事后荟萃分析。通过群体测序分析基线HCV NS3/4A蛋白酶序列以确定Q80K流行率。总体而言,在分析的来自欧洲地区25个国家的3349例患者中,分别有35.8%、63.8%和0.3%的患者为G1a、G1b和其他/未知的HCV G1亚型。总体上,7.5%的HCV G1患者在基线时检测到Q80K。按亚型检查显示,G1a、G1b和其他/未知HCV G1亚型患者中分别有19.8%、0.5%和18.2%具有Q80K多态性。在欧洲地区有⩾20例G1a患者和/或⩾40例总体G1患者测序数据的国家中,G1中Q80K的流行率在保加利亚为0%至英国的18.2%之间。Q80K流行率在不同国家的G1a中也有所不同。通过LiPA v2检测法,99%的患者HCV亚型1a被正确确定。与北美相比,在欧洲地区HCV G1感染患者中观察到Q80K总体流行率较低。然而,由于G1a/G1b比例不同以及G1a人群中Q80K流行率不同,流行率因国家而异。

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