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白细胞介素 28B 多态性预测聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎基因型 4 的疗效。

Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4.

机构信息

Centro AM e A Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.

出版信息

Hepatology. 2012 Feb;55(2):336-42. doi: 10.1002/hep.24683. Epub 2012 Jan 3.

Abstract

UNLABELLED

Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too is unknown. The aim was to investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for nonvirologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT (P < 0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% versus 23, 29%; P = 0.08), while also showing lower relapse rates (0% [0/21] versus 36% [16/45] P = 0.0013). In non-RVR patients, SVR rates were higher in CC than CT/TT patients (9 [75%] versus 13 [23%] P = 0.001). By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 8.0 (95% confidence interval 2.00-32.01; P = 0.003).

CONCLUSION

The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients because it is the strongest predictor of an SVR to PegIFN/Rbv therapy.

摘要

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白细胞介素 28B(IL28B)区域附近的单核苷酸多态性(SNPs)是丙型肝炎病毒(HCV)基因型 1 感染患者对聚乙二醇干扰素(PegIFN)和利巴韦林(Rbv)持续病毒学应答(SVR)的最强基线预测因子。对于 HCV-4 患者是否也是如此尚不清楚。目的是研究 rs12979860IL28B SNP 对 HCV-4 患者对 Peg-IFN 和 Rbv 反应的预测能力。2004 年 9 月至 2010 年 6 月期间,米兰马焦雷医院(意大利)的两个肝脏中心连续治疗的所有 HCV-4 患者均接受 TaqMan SNP 基因分型检测以检测 rs12979860 基因型。在 112 例接受治疗的患者(98 名男性,75 名埃及血统,26 名肝硬化)中,103 例纳入最终分析;5 例因非病毒原因停药,4 例不同意基因检测。24 例(23%)为 CC 基因型,65 例(63%)为 CT,14 例(14%)为 TT。总的来说,50 例(49%)获得 SVR:21 例(88%)CC 患者与 29 例(37%)CT/TT(P <0.0001)。CC 患者比 CT/TT 患者更常发生快速病毒学应答(RVR)(12 例,50%对 23 例,29%;P=0.08),而复发率也较低(0%[0/21]对 36%[16/45];P=0.0013)。在非 RVR 患者中,CC 患者的 SVR 率高于 CT/TT 患者(9[75%]对 13[23%];P=0.001)。通过逻辑回归,白细胞介素 28B rs12979860CC 基因型是 SVR 的独立预测因子,优势比为 8.0(95%置信区间 2.00-32.01;P=0.003)。

结论

白细胞介素 28B rs12979860 SNP 可能在 HCV-4 患者的治疗方案中具有附加价值,因为它是 PegIFN/Rbv 治疗 SVR 的最强预测因子。

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