Homozygosity for HLA Group 2 Alleles Predicts Treatment Failure with Interferon-α and Ribavirin in Chronic Hepatitis C Virus Genotype 1 Infection

Abstract

Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors

“…IFNL3 rs12979860 single nucleotide polymorphism (SNP) analysis was performed by allelic discrimination real-time PCR as described previously [ 12 ]. HCV genotyping was performed by Innogenetics VERSANT HCV genotype 2.0 (Siemens Healthcare, Milan, Italy) or the RealTime HCV Genotype II (Abbott Molecular Laboratories, Wiesbaden, Germany) assays.…”

Naturally Occurring HCV NS5A/B Inhibitor Resistance-Associated Mutations to Direct-Acting Antivirals

“…HCV viral load was measured using Abbott Molecular m2000 RealTime System (Wiesbaden, Germany). IFNL3 (formerly IL28B) rs12979860 single nucleotide polymorphism analysis was performed by allelic discrimination real-time PCR as described [3]. Subtype identification based on NS3 sequencing was performed as previously reported [4].…”

“…Linh Thuy Nguyen 1,2,3 * † , Naomi Hall 2,4 † , Dylan Sheerin 2,5 † , Michael Carr 2 , Cillian F De Gascun 2,3 , the Irish Hepatitis C Outcomes Research Network ‡ Introduction region. Consequently, and in light of the significant monetary cost of DAA-based regimens, the role of baseline screening for HCV polymorphisms -as a means of informing national treatment policies -remains to be definitively ascertained.…”

Interferon lambda rs368234815 ΔG/ΔG is associated with higher CD4+:CD8+ T-cell ratio in treated HIV-1 infection

“…IFNL genotyping was performed employing TaqMan SNP genotyping allelic discrimination on the ABI 7500 Fast instrument (Applied Biosystems, Warrington, United Kingdom). Assay conditions and thermocycling parameters for allelic discrimination real-time polymerase chain reaction (PCR) were as previously described for rs12979860 and validated by Sanger sequencing [18] and the rs368234815 SNP genotyping assay was supplied by Applied Biosystems. All genotyping was undertaken with blinding to clinical variables.…”

“…Several polymorphisms near the type III interferon lambda (IFNL3) locus, previously named interleukin 28B (IL28B), are able to predict both spontaneous clearance of hepatitis C infection by the host as well as better responses to pegylated interferon-alpha/ribavirin (PEG/RBV) therapy for HCV infection [14][15][16][17]. Similarly, the rs12979860 C>T single nucleotide polymorphism (SNP) is associated with higher HCV RNA titers and improved response to PEG/RBV therapy in those carrying the CC major homozygous genotype [14,18,19]. The rs12979860 polymorphism displays high linkage disequilibrium with a dinucleotide/deletion variant (TT/∆G) rs368234815 (TT>ΔG) [20].…”