A predictive model of treatment outcome in patients with chronic HCV infection using IL28B and PD-1 genotyping

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• 作者：Jose Ramó ; n Vidal-Casti&ntilde ; eira¹ ; Antonio Ló ; pez-Vá ; zquez¹ ; Rebeca Alonso-Arias¹ ; Marco Antonio Moro-Garcí ; a¹ ; Pablo Martinez-Camblor⁶ ; Santiago Meló ; n² ; Jesú ; s Prieto³ ; Rosario Ló ; pez-Rodriguez⁴ ; Paloma Sanz-Cameno⁴ ; Luis Rodrigo⁵ ; Rosa Pé ; rez-Ló ; pez⁵ ; Ramó ; n Pé ; rez-Á ; lvarez⁵ ; Carlos Ló ; pez-Larrea¹ ; ⁷ ; ^{inmuno@hca.es}
• 关键词：HCV ; hepatitis C virus ; PD-1 ; Programmed Cell Death-1 ; Peg-IFN ; pegylated interferon ; KIR ; killer immunoglobulin-like receptors ; HLA ; human leukocyte antigens ; SVR ; sustained virological responders ; NR ; non responders ; CTL ; cytolytic T lymphocytes ; HC ; he
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：June, 2012
• 卷：56
• 期：6
• 页码：1230-1238
• 文件大小：870 K

摘要

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Background & Aims

The advent of new chronic hepatitis C virus (HCV) therapies requires characterization of patients in order to predict adequate treatment. A good candidate marker is Programmed Cell Death-1 (PD-1) which is involved in progression of HCV infection. The aim of this study was to analyse the effect of several single nucleotide polymorphisms of PD-1 gene and several previously associated factors (IL28B and KIR receptors) on treatment responses.

Methods

407 HCV chronic infected patients treated with PEG-IFN-伪 and ribavirin were recruited and classified according to their response to treatment. They were genotyped for PD-1 and IL28B polymorphisms, killer immunoglobulin-like receptors (KIR) and HLA genes. A multivariate logistic regression analysis and a Chi-squared Automatic Interaction Detector (CHAID) prediction model of response included these and other clinical parameters.

Results

Our results showed that PD-1.3/A allele was significantly associated with sustained virological response (SVR) in a multivariate logistic regression analysis (p <0.01, OR = 2.57). Additionally, IL28B C/C genotype was the most significant predictor of an SVR to treatment in all HCV genotypes (74.5%). In IL28B C/C patients, the presence of PD-1.3/A allele increased the probability of an SVR to 93.3%. Moreover, when this analysis was made only with patients infected by HCV-1, the predictive value of IL28B C/C genotype with PD-1.3/A allele was 90%.

Conclusions

PD-1.3/A allele is associated with SVR to treatment and notably increases the predictive value of IL28B C/C genotype. Both markers in conjunction could be a useful tool, more relevant than HCV genotype in some cases, in clinical practice.