Article Text

Download PDFPDF

P58 Genetic, virological and immunological pre-treatment predictors of therapy response to Peg-IFN/ribavirin in children with chronic hepatitis C
  1. I Carey,
  2. M Bruce,
  3. S Bansal,
  4. S Tizzard,
  5. D Joshi,
  6. D Vergani,
  7. G Mieli-Vergani
  1. Institute of Liver Studies, King's College Hospital NHS Foundation Trust, UK


Introduction Vertically acquired chronic hepatitis C (CH-C) is a mild disease in childhood but may accelerate in adolescence. Effective early therapy with pegylated interferon (Peg-IFN) and ribavirin (Riba) prevents progressive liver damage. Control of HCV infection depends on both innate and adaptive immunity. Little is known about treatment predictors in children with CH-C.

Aim To assess whether single nucleotide polymorphisms (SNP) near IL28B gene rs12979860 and rs8099917, HCV genotype (G) and pre-treatment innate and adaptive immunity [frequency/phenotype of natural killer (NK) cells, HCV-specific T cell responses, frequency/phenotype of T regulatory cells (T-regs), plasma levels of IFN-γ inducible protein 10 (IP-10)] predict therapy response in children with CH-C.

Method Patients: 32 children with CH-C (19 males, median age 12 yrs, 53% G1) treated according to genotype with Peg-IFN (60 μg/m2/week) and riba (15 mg/kg/d) were divided into responders (22, R), relapsers (4, Rel) and non-responders (6, NR).

Methods: rs12979860 and rs8099917 were tested by direct sequencing; baseline numbers of NK cells (CD3-CD56+) and their subsets CD56dim/CD56bright, CD3CD56+/−CD16+/−, of CD4+cells expressing programmed death receptor (CD4+PD1+) and of T-regs (CD4+CD25+FoxP3+) by flowcytometry on peripheral blood mononuclear cells (PBMC). PBMC IFN-γ and IL-10 production after exposure to HCV-core, NS3, NS4, NS5 antigens was evaluated by intracellular cytokine staining. Baseline IP-10 plasma levels [pg/ml] were measured by ELISA. All presented as median.

Results rs12979860 haplotype CC was present in 34% (91% R and 9% NR), CT in 47% (73% R, 7% Rel and 20% NR) and TT in 19% (17% R, 50% Rel and 33% NR); rs8099917 haplotype TT was seen in 50% (88% R and 12% NR), GT in 44% (50% R, 29% Rel and 21% NR) and GG in 6% (50% R and 50% NR) patients. Non-G1 CH-C was linked with better response than G1 (53% vs 80%, p=0.02). Baseline number of CD56bright NK cells was higher in R than Rel & NR (3.7% vs 1.8% and 1.3%, p=0.05). Compared to R, Rel and NR had higher numbers of CD3-CD56-CD16 cells (17.4% vs 12.9% & 10.7%, p=0.05), of HCV-core-specific IL-10 producing cells (CD4+/IL-10: 4.4% and 3.8% vs 1.7%, p=0.03), of CD4+PD1+ cells (7.1% and 6.9% vs 4.3%, p=0.03) and of T-regs (4.2% and 3.0% vs 1.4%, p=0.04). Baseline plasma IP-10 levels were higher in NR than Rel and R (85 vs 34 and 15, p<0.01). By multivariate analysis only possession of CC rs12979860 and TT rs8099917 haplotypes and low baseline IP-10 levels were associated with response to therapy.

Conclusion Possession of both major haplotypes CC rs12979860 and TT rs8099917 for IL28B gene SNPs and low baseline IP-10 levels predict successful therapy response in children with CH-C.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.