Source Im munology Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
BACKGROUND & AIMS: The arrival 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 (IL-28B and KIR receptors) on treatment responses.
METHODS: 407 HCV chronic infected patients treated with PEG-IFN-α and ribavirin were recruited and classified according to their response to treatment. They were genotyped for PD-1 and IL-28B polymorphisms, Killer immunoglobulin-like receptors (KIR) and HLA genes. A multivariate logistic regression analysis and a 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, IL-28B C/C genotype was the most significant factor predicting a SVR to treatment in all HCV genotypes (74.5%). In IL-28B C/C patients, the presence of PD-1.3/A allele increased the probability for a SVR to 93.3%. Moreover, when this analysis was made only with patients infected by HCV-1, the predictive value of IL-28B 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 IL-28B C/C genotype. Both markers in conjunction could be a useful tool, more relevant in some cases than HCV genotype in clinical practice.