‘Favourable’ IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype 3a infection and do not predict a sustained virological response after 24 weeks of therapy

Abstract

'Favourable' IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype 3a infection and do not predict a sustained virological response after 24 weeks of therapy IL28B host genetic make-up is known to play a critical role in the outcome of genotype 1 hepatitis C virus (HCV) infection in the context of both primary infection and therapy. However, the role of IL28B in subtype 3a infection remains unclear, and has not yet been assessed in the UK population where subtype 3a is dominant. In this study, we evaluated the role of the IL28B singlenucleotide polymorphism rs8099917 in 201 patients recruited from two well-defined cohorts (from Nottingham and Oxford), treated with the standard-of-care therapy of pegylated interferon and ribavirin for 24 weeks. We showed that the 'favourable' IL28B gene was associated with a rapid virological response to therapy at 4 weeks (P,0.0001), but not with a sustained virological response to therapy. The median viral load at baseline, before therapy, was markedly increased in people with the 'favourable' IL28B genotype [median viral load for the TT allele, 925 961 IU ml "1(range 2200-21 116 965 IU ml "1 ), and for the GT or GG allele, 260 284 IU ml "1 (range 740-7 560 000 IU ml "1 ); P50.0010]. Our results suggest that the host genetic response plays an important role in early viral clearance of subtype 3a virus from the blood. However, significant reservoirs of infection must persist, as viral relapse is common, even in those with the favourable host genotype.

Association of IL28B single nucleotide polymorphism rs8099917 with response to treatment in genotype 3 HCV-infected patients from India

“…20,25 In our cohort even though the relapse rate was as high as 20% ( Table 3) there was no association of rs8099917 with relapse (p=0.420). These results suggest that similar to SNP with both RVR and SVR.…”

“…Several studies have shown association of IL28B SNPs with RVR in genotype 3 HCV infections, but no significant association has been seen with SVR. 20,24,25 Mangia et al from Italy genotyped ~300 chronic HCV genotype 2/3 infected patients who received standard combination therapy. They were tested for associationsbetween rs12979860 genotypes and RVR and SVR.…”

“…[15][16][17][18]20,[23][24][25] Relapse after therapy is an important concern in genotype 3 HCVinfection. 20,25 It has been suggested the duration of therapy may need to be individualized in genotype 3 infections. 26,27 Importantly, the association of IL28Bpolymorphismswith treatment outcome in genotype 3 HCV patients from India has not been studied.…”

“…20,25 Three previous studies have showed significant association between SVR and IL28B SNPs, [29][30][31] although these studies involved only genotype 2 or genotype 2/3 HCV patients.…”

The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways

“…Viral genotype is emerging as a central determinant of whether the above polymorphisms can exert any influence on viral clearance; for example variants of IFN‐λ3/4 play a limited role in predicting HCV related outcomes in patients infected with HCV G2/3 23. Recent work has suggested this may be a result of genotype 1 viral infection inducing transcripts which are heavily regulated by IFN‐λ3/4, whereas HCV G2/3 infection leads to the upregulation of genes induced by IFN‐γ 24.…”