Spontaneous clearance of hepatitis C virus (HCV) occurs in ~30% of acute infections [1
]. Several host factors are determinants of spontaneous clearance including race, sex, human immunodeficiency virus (HIV) and hepatitis B virus coinfection status, and host genetics [1
]. The strongest genetic factor associated with spontaneous clearance described to date is single-nucleotide polymorphisms (SNPs) around IL28B
, in particular rs8099917 and rs12979860 (reviewed in [3
]). These SNPs have been studied largely in African American and white populations, which are primarily infected with HCV genotypes 1, 2, and 3 [4
]. It is not known whether the SNPs in this genomic region are also important in spontaneous clearance of other genotypes from other areas of the world. Such information may be helpful in understanding the mechanism of potential involvement of interleukin 28B (IL28B), a type III interferon (IFN), also called IFN-λ3, on HCV clearance.
Egypt has the highest HCV prevalence in the world. An estimated 10%–20% of the Egyptian population is chronically HCV infected, a seroprevalence that is ~10- to 20-fold higher than in the United States. More than 90% of HCV infections in Egypt are genotype 4, which is found primarily in the Middle East and Central Africa and has a worldwide prevalence of 2% [6
The C allele of rs12979860, which is ~3 kb upstream of IL28B,
is associated with a favorable response to HCV treatment in patients with genotype 4 infection [8
]; however, the effects of this SNP in spontaneous clearance of genotype 4 is unknown. In addition, the prevalence of the favorable C allele in North Africa has never been investigated even though its prevalence in African Americans and in Africans from southern Africa is significantly lower than in whites [4
In this study, we tested the hypothesis that rs12979860 is associated with spontaneous clearance of genotype 4 HCV in a North African population. To test this hypothesis, we used a prospectively followed up Egyptian cohort that was well characterized in terms of the natural outcome of HCV infection (clearance vs persistence).