The distribution of polymorphisms in the IL28B gene in previously untreated Australian patients with genotype 1 CHC: The predict study.

Abstract

Background Polymorphisms near the IL28B gene strongly predict the likelihood of achieving a sustained virological response to pegylated interferon and ribavirin therapy in chronic hepatitis C (CHC) patients, and spontaneous viral clearance. In addition, variations in the allelic frequency of SNPs near the IL28B gene largely explain ethnic-specific differences in SVR rates. In Australia, over 4000 patients with CHC are treated annually but the correlation of IL28B genotypes with patient demographics and disease characteristics is unknown. Aims The Aim of the present study (PREDICT) was to examine the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) in previously untreated patients with genotype 1 (Gt1) CHC being considered for anti-viral therapy. Methods The study was a prospective, multicentre, single arm observational non-interventional study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects were 18 years and over, had Gt1 CHC, were treatment naive, and being considered for treatment. IL28B SNPs were genotyped by the Applied Biosystems's Taqman SNP genotyping assay. Results Between May 2011 and May 2012, 902 patients from 40 clinics across all Australian states were recruited to the study. Of these, 64% were male, with the median age being 49 (range 18-80) years. The majority (86%) were of Caucasian ethnicity, while the percent of Asian, Mediterranean, Aboriginal, Middle Eastern, Hispanic, Indian, African and Pacific islanders were 5%, 3%, 3%, 1%, 1%, <1%, <1%, and <1%. Of those in whom data was available (833/902), 49% were Gt1a, 21% 1b, 5% 1a/1b and 26% Gt1 (no subtype). The frequency of the IL28B rs12979860 CC/CT/TT genotypes was 34%, 53% and 13% and that of rs8099917 TT/ GT/GG, 53%, 42% and 5%, respectively. In self identified Caucasians, the prevalence of the IL28B rs12979860 CC genotype was 27%, while in Asians it was 79% and in Mediterranean's 18%. The prevalence of the IL28B rs8099917TT genotype was 43% in Caucasians, 81% in Asians and 25% in Mediterranean's. To date, 141 patients have commenced treatment, and outcome data is awaited. Conclusion A large number of Australian Clinics have successfully enrolled CHC Gt1 patients to the PREDICT study. The majority of enrolled patients had HCV Gt1a, while a higher proportion of Asians than Caucasians had the IL28B responder genotype. Data on the relationship of IL28B genotype to treatment response, and patient and physician attitudes to the genotyping results and its impact on therapeutic decision making are awaited.