Published online Jul 28, 2014. doi: 10.3748/wjg.v20.i28.9245
Revised: February 24, 2014
Accepted: May 23, 2014
Published online: July 28, 2014
Processing time: 284 Days and 14.7 Hours
The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in adults have demonstrated that genetic variation in IFNL3 is a strong predictor of the virological response in treatment-naive patients with HCV genotype 1 who were treated with Pegylated-IFN-α and ribavirin. Genetic variation in IFNL3 is also associated with the spontaneous clearance of HCV. Thus far, few paediatric studies have explored the association between variations in the IFNL3 gene and either spontaneous or treatment-induced clearance of HCV. The CC genotype of the rs12979860 SNP is associated with the spontaneous clearance of HCV in children independently of HCV genotype. Four paediatric studies have shown that both the CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-α and ribavirin association) clearance of HCV, while the rs12980275 SNP did not affect the virological response. The possible role of IFNL3 gene variation as a pre-treatment and on-treatment predictor of virological response in children is highly attractive but still undetermined. Further paediatric studies are needed to evaluate if testing for SNPs in IFNL3, either alone or together with other predictors of response to treatment, could be used to direct treatment strategies, including an avoidance of unnecessary protease inhibitor therapy and the duration of treatment.
Core tip: Single nucleotide polymorphisms in the interferon L3 (IFNL3) gene have been associated with both spontaneous and treatment-induced clearance of hepatitis C virus in children. Data from adult studies suggest a role of IFNL3 testing in the decision-making process of whether to treat a patient, the use of two or three drugs and whether the standard duration of treatment or a shorter duration should be proposed. These options are attractive if applicable to children. While waiting for the approval of new interferon-free regimens, paediatric collaborative studies to evaluate the possible role of genetic polymorphisms of IFNL3 as pre-treatment and on-treatment predictors of response, alone or together with other predictors, are highly needed.