Abstract
BackgroundRecent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients.AimsThe aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects.Methods and patientsWe enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects.ResultsCC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03).ConclusionsFemale subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile.
Highlights
Hepatitis C virus (HCV) is a positive-stranded RNA virus and one of the most common blood borne infectious agent worldwide
CC, CT and TT-genotypes of the single-nucleotide polymorphism (SNP) rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared hepatitis C virus (HCV) and in 31%, 54% and 15% of controls, respectively (p = 0.0003)
Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03)
Summary
Hepatitis C virus (HCV) is a positive-stranded RNA virus and one of the most common blood borne infectious agent worldwide. HCV infection induces a wide range of innate and adaptive immune responses [1,2] but eventually the majority of infected individuals develop chronic HCV infection, while only approximately 30–40% of them spontaneously clear the virus [3] In these subjects, serum anti-HCV antibodies remain detectable for a long time without evidence of circulating HCV-RNA. Recent genome-wide association studies (GWAS) have shown a single-nucleotide polymorphisms (SNPs) around the gene coding for IFN-l-3 (or IL28B), located on chromosome 19q13, to be associated with spontaneous virus clearance in patients with HCV infection. IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients
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