Genetic polyporphism of IL28B gene and spontaneous clearance of hepatitis C virus in c hildren
Giuseppe Indolfi1, Giusi Mangone2, Pier Luigi Calvo3, Elisa Bortolini1, Marta Regoli1, Daniele Serranti4, Carmelina Calitri3, Pier Angelo Tovo3, Maurizio de Martino4, Chiara Azzari2, 3, Massimo Resti1
1Paediatric and Liver Unit, Meyer Children΄s University Hospital of Florence, Italy, Florence, Italy; 2Immunology Unit and Laboratory of Meyer Children΄s University Hospital of Florence, Italy, Florence, Italy; 3Department of Pediatrics, Infectious Diseases Unit, University of Turin, Regina Margherita Children's Hospital, Turin, Italy, Turin, Italy; 4Department of Health Sciences, University of Florence, Italy, Florence, Italy
Spontaneous clearance of hepatitis C virus (HCV) occurs in 8-20% of the infected children. Over half of the children who undergo spontaneous clearance of the infection are infected by HCV genotype 3, and develop an aminotransferase peak at the onset of the infection. Recent genome-wide association studies performed in adults documented that single nucleotide polymorphisms (SNPs, rs12979860 and rs8099917) located on chromosome 19, upstream of the interleukin (IL) 28B gene which encodes the type III interferon (IFN)-λ3 were associated with spontaneous clearance of hepatitis C virus HCV and with response to treatment with pegylated interferon and ribavirin. Preliminary results on small cohorts of children seem to confirm this association. The aim of the present collaborative study was to evaluate the role of rs12979860 single nucleotide polymorphisms in predicting spontaneous clearance of hepatitis C virus in a large cohort of Italian children. One hundred and fifty three consecutive children (median age 14.6 years, IQR 10.2) regularly followed-up in two Italian pediatric hospitals, the Meyer Children΄s University Hospital of Florence and the Regina Margherita Children΄s Hospital of Turin, were enrolled and genotyped. Spontaneous clearance of HCV was defined in children older than 18 months of age when polymerase chain reaction for HCV ribonucleic acid was negative and HCV antibodies were positive in at least three blood samples taken 6 months apart; positive polymerase chain reaction for HCV ribonucleic acid and HCV antibodies defined chronic hepatitis C. One hundred and thirty children (86.7%) were chronically infected while 23 (13.3%) had spontaneous clearance of the virus. The IL28 C/C and C/TT/T genotypes were found in 57 (37.3%) and 96 (62.7%) children, respectively. Children with the C/C genotype (14/57; 24.6%) were 3 times more likely to clear hepatitis C virus than those with the C/T and T/T genotypes combined (9/96; 9.4%; odds ratio 3.15; 90% confidence intervals 1.34-7.53; p 0.01). The highest clearance rate was found among C/C children (24.6%), an intermediate clearance rate among heterozygous C/T (8/70; 11.4%; odds ratio 2.52; 90% confidence intervals 1.03-6.3 versus CC; p 0.05) and the lowest rate in the T/T homozygous children (1/26; 8.14%; odds ratio 2.52; 90% confidence intervals 1.27-132.98 versus CC; p 0.02). Results of this study carried out on 153 children with HCV infection demonstrated that IL28B rs12979860 C/C SNP was associated with spontaneous clearance of HCV also in the pediatric age.
The following people have nothing to disclose: Giuseppe Indolfi, Giusi Mangone, Pier Luigi Calvo, Elisa Bartolini, Marta Regoli, Daniele Serranti, Carmelina Calitri, Pier-Angelo Tovo, Maurizio de Martino, Chiara Azzari, Massimo Resti