Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV‐infected children

Abstract

The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA1ve / human immunodeficiency virus negative (HIV2ve), with 128 children, and 33 were HCV-RNA2ve/HCV antibody1ve, with 43 children. The infants were tested for HCV-RNA at birth and at regular intervals until the age of 6 years. IL28B (single nucleotide polymorphism rs12979860) was determined in the mothers and children. HCV-VT was assumed when children presented HCV-RNA1ve in two subsequent blood samples. HCV-VT-infected infants were categorized as: (1) transient viremia with posterior HCV-RNA2ve and without serum-conversion; (2) persistent infection with serum-conversion. Of the 31 mothers with CC polymorphism, 19 (61%) were HCV-RNA1ve, whereas among the 68 mothers with non-CC polymorphism, 56 (82%) were HCV-RNA1ve. In all, 26 of 128 (20%) infants born to the HCV-RNA1ve mothers acquired HCV infection, but only 9 (7%) were chronically infected. The rate of HCV-VT was higher among the mothers with higher HCV viremia. No HCV-VT was detected in the HCV-RNA2ve women. Neither the mothers' nor the childrens' IL-28 status was associated with an increased risk of HCV-VT. The factors influencing viral clearance among the infected children were genotype non-1 and genotype CC of IL28B. In logistic regression, child CC polymorphism was the only predictor of HCV-clearance in HCV genotype-1. Conclusion: High maternal viral load is the only predictive factor of HCV-VT. IL28B plays no role in HCV-VT, but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype-1 among infected children. (HEPATOLOGY 2011;53:1830-1838

Characterization of the Interleukin-28B Gene rs12979860 C/T Polymorphism in Turkish Chronic Hepatitis C Patients and Healthy Individuals

“…They found a tendency (p=0.0813) towards a higher frequency of allele T in the group of patients according to the controls, but no significant difference in the genotypic frequency (p=0.1865) was found between the two groups. In other studies, the CC genotype played a major role in viral clearance caused by treatment (34,35). In our study, 44.6% of the cases in the control group were CC, 46.7% of the cases were CT, and 8.7% were TT.…”

Reply to the correspondence letter by Dr. Giuseppe Indolfi “Spontaneous clearance of hepatitis C virus in vertically infected children. Any clue for treatment?”

“…In our six patients, the combination of the longitudinal course of LFTs plus HCV gene copy number appeared to aid in predicting the chance of viral resolution. As mentioned in our paper, we concur that other features of HCV infection, such as viral genotype and IL28B polymorphisms, contribute to viral resolution in children [1,3,4]. Therefore, information on IL28B polymorphisms in our patients would have been interesting.…”

Association of the interleukin-28B gene polymorphism with development of hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta-analysis

“…Besides, several global stud ies have revealed that the C/C genotype is the major player in drug-induced viral clearance, while both the C/T and T/T genotypes have a poor association with clearance rates (Liao et al, 2011;Ruiz-Extremera et al, 2011). Similarly, host factors control tolerance to chronic HBV infection and can fluctuate over time with increased risk of progression to cirrhosis and particularly HCC (Eksteen, 2011).…”