Abstract
Background and purposeContradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients.MethodsA total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records.Results2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection.ConclusionThis large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3663-6) contains supplementary material, which is available to authorized users.
Highlights
Background and purposeContradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC)
Host interleukin-28B (IL28B) genotype is associated with spontaneous clearance of acute hepatitis C virus (HCV) infection, response to interferon (IFN)-based treatment, and with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) (Thomas et al 2009; Ge et al 2009; Zhang et al 2016)
Genome-wide association studies have identified singlenucleotide polymorphisms (SNPs) in close proximity to the IL28B gene that encode for IFN lambda (IFN-λ), with strong associations with spontaneous or IFN-induced clearance of HCV (Thomas et al 2009; Ge et al 2009; Rauch et al 2010; Suppiah et al 2009; Tanaka et al 2009)
Summary
Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. Host interleukin-28B (IL28B) genotype is associated with spontaneous clearance of acute hepatitis C virus (HCV) infection, response to interferon (IFN)-based treatment, and with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) (Thomas et al 2009; Ge et al 2009; Zhang et al 2016). Other studies have yielded contradictory results on the association between IL28B genotype and fibrosis progression (Asselah et al 2012; Falleti et al 2011; Fabris et al 2011; Marabita et al 2011; Di Marco et al 2012; D’Ambrosio et al 2014)
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