IL28B SNP rs8099917 Is Strongly Associated with Pegylated Interferon-α and Ribavirin Therapy Treatment Failure in HCV/HIV-1 Coinfected Patients

Abstract

Recent genome-wide association studies report that the SNP rs8099917, located 8.9 kb upstream of the start codon of IL28B, is associated with both disease chronicity and therapeutic response to pegIFN-α and RBV in patients infected with genotype 1 HCV. To determine the effect of rs8099917 variation on the response of HCV to therapy, we genotyped this variant in a cohort of 160 HCV/HIV-1 coinfected patients in our clinic unit who received combined peg-IFN-α/RBV therapy. The rs8099917 T/G or G/G genotypes were observed in 56 patients (35%). Treatment failure occurred in 80% of G-allele carriers versus 48% of non-carriers (P<0.0001). This result reveals that the G allele was strongly associated with treatment failure in this patient cohort. Importantly, a highly significant association was found between the G-allele and response to therapy in HCV genotype 1-infected patients (P<0.0001) but not in HCV genotype 3-infected patients. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated that the rs8099917 TT genotype was a strong predictor of treatment success (5.83; 1.26–26.92; P = 0.021), independent of baseline plasma HCV-RNA load less than 500 000 IU/ml (4.85; 1.18–19.95; P = 0.025) and absence of advanced liver fibrosis (5.24; 1.20–22.91; P = 0.025). These results reveal the high prevalence of the rs8099917 G allele in HCV/HIV-1 coinfected patients as well as its strong association with treatment failure in HCV genotype 1-infected patients. rs8099917 SNP genotyping may be a valid pre-treatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HIV-infected patients.

Distribution of polymorphisms rs12979860, rs8099917 and rs12980275 IL28B in patients with chronic hepatitis C

“…8 Among the examined patients from the Wielkopolska Province, the occurrence of at least 1 of the preferred variants was noted in 591 cases. The most frequent advantageous variant was TT rs8099917 reported in 43.5% of the patients; almost all of these patients were the carriers of profitable variant CC rs12979860 (except 2 patients).…”

“…7 Further research on the effectiveness of antiviral therapy in the patients with chronic hepatitis C led to the discovery that the profitable course of treatment in the case of polymorphism rs8099917 (T/G) is observed in the patients with genotype TT, while for polymorphism rs12980275 (A/G ) these observations apply to the patients with genotype AA. 8 Profitable variants may determine the phenomenon of spontaneous HCV elimination, but do not provide the resistance to infection upon exposure. It was demonstrated, based on observations of the group of patients after the exposure to hepatitis C virus, that the presence of variant CC does not protect against an acute infection, whereas homozygocity for KIR2DL3:HLA-C1 provides such protection.…”

“…[13][14][15] This is explained by the hypothesis that the variant TT may have a protective effect against acute infection occurrence. 8 Comparison of the frequency of particular variants in different research studies reveals significant discrepancies. This depends on the selection of the examined group: ethnicity of the patients, accompanying HIV or HBV infection, disease severity -patients with newly diagnosed infection by screening, or patients with chronic infection qualified to the treatment, patients not responding to standard treatment.…”

Interleukin 28b Gene Polymorphisms as a Predictor of Treatment Response in Egyptians With Chronic Hepatitis C.

“…In a study by Aparicio et al, (2010) 6 , patients carrying rs8099917 G alleles had high rates of treatment failure. The rate of treatment failure in patients infected with HCV genotype 3 was not affected by rs8099917 genotype.…”

Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C, low grade of hepatic fibrosis, genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study

“…Italian cohort) were associated with a greater likelihood of HCV persistence, particularly in HCV GT1 and GT4 (Aparicio et al, 2010;Bitetto et al, 2011;Boglione et al, 2015;Boglione et al, 2014).…”