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Abstract Details
'Favourable' IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype-3a infection and do not predict sustained virological response after 24 weeks of therapy
Bucci C, von Delft A, Cristian A, Flemming VM, Harrison A, Halliday J, Collier J, Manganis C, Klenerman P, Irving W, Barnes E. J Gen Virol. 2013 Mar 13. [Epub ahead of print]
Source
The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK;
Abstract
IL28B host genetic make up is known to play a critical role in the outcome of genotype-1 HCV infection in the context of both primary infection and also 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 evaluate the role of the IL28B SNP (rs8099917) in 201 patients recruited from two well defined cohorts (Nottingham and Oxford), treated with standard of care therapy pegylated-interferon and ribavirin for 24 weeks. We show that the 'favourable' IL28B gene is associated with a rapid virological response to therapy at 4 weeks, (p<0.0001) but not with a sustained virological response to therapy. Median viral load at baseline, before therapy, was markedly increased in people with the favourable IL28B genotype (median viral load for TT allele 925,961 IU/ml (range 2200-21,116,965 IU/ml) and for GT/GG allele 260,284 IU/ml (range 740-7,560,000 IU/ml) p=0.0010).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 since viral relapse is common even in those with the favourable host genotypes.