A predictive model of treatment outcome in patients with chronic HCV infection using IL28B and PD-1 genotyping.
OBJECTIVE
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-α 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.
Immunology Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
Jose Ramón
JR
Vidal-Castiñeira
Antonio
A
López-Vázquez
Rebeca
R
Alonso-Arias
Marco Antonio
MA
Moro-García
Pablo
P
Martinez-Camblor
Santiago
S
Melón
Jesús
J
Prieto
Rosario
R
López-Rodriguez
Paloma
P
Sanz-Cameno
Luis
L
Rodrigo
Rosa
R
Pérez-López
Ramón
R
Pérez-Álvarez
Carlos
C
López-Larrea
D000328:Adult; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D016896:Treatment Outcome; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; D061026:Programmed Cell Death 1 Receptor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C105992:PDCD1 protein, human