IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection

Abstract

Chronic hepatitis C virus (HCV) infection patients exhibit different sustained virological responses (SVRs) following the treatment with pegylated interferon-α (IFN-α) and ribavirin. Genome-wide association studies consistently linked SVR of IFN-α-based therapy to the IL28B single-nucleotide polymorphisms (SNPs) on chromosome 19q.13 in various populations. This study was undertaken to investigate the association of IL28B SNPs with SVR in a cohort of Taiwanese chronic HCV patients. Ten SNPs of IL28B were genotyped in 728 chronic HCV patients and 960 healthy controls. Genotype distributions, allele frequencies and haplotypes were tested for SVR and susceptibility in Taiwanese chronic HCV patients. Non-genotype 1 infection (adjusted P=3.3 × 10−12, odds ratio (OR) 0.179; 95% confidence interval (CI): 0.110–0.290) and low HCV viral load (<400 000 IU ml–1) (adjusted P=3.5 × 10−9, OR 0.299; 95% CI: 0.200–0.446) were two major factors identified for high SVR. Notably, eight IL28B SNPs including previously described disease-associated SNPs (Trend test P=0.005) were significantly associated with SVR. Our data indicate that IL28B polymorphisms are the essential contributing factors for high SVR in Taiwanese chronic HCV patients. Combination of virus genotyping and host genetic data may be used to select the optimal treatment regimes in IFN-based therapy.

Two IL28B polymorphisms are associated with the treatment response of different genotypes of hepatitis C in different racial populations: A meta-analysis

“…As shown in Table I, 16 studies (10,13,21-34) were eligible for examining the association between the IL28B polymorphism rs8099917 and treatment response of hepatitis C, including 3,540 cases with SVR and 2,208 cases with non-SVR. As shown in Table II, 17 studies (4,10,17,21,(27)(28)(29)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) were eligible for examining the association between the IL28B polymorphism rs12979860 and treatment response of hepatitis C, including 2,951 cases with SVR and 2,506 cases with non-SVR.…”

“…For rs8099917, patients with the TT genotype (2,819/4,106) had a higher rate of SVR than G allele carriers (721/1,642) from 16 studies (TT vs. TG/GG, OR=2.29, 95% CI 1.74-3.01, P<0.001 for heterogeneity). Of these 16 studies, seven (21,25,26,28,(30)(31)(32) examined the association between IL28B polymorphism rs8099917 and the SVR rate in an Asian population, and the other nine in a European population. The SVR rate in Asian patients (2,160/3,426) was higher than that in European patients (1, Table I.…”

“…This meta-analysis showed that patients with the homozygous CC genotype (1,838/2,666) had a significantly higher SVR rate for HCV than T allele carriers (1,113/2,791) (CC vs. CT/TT, OR=2.91, 95% CI 2.13-3.98, P<0.001 for heterogeneity). Of these 17 studies, three (4,36,41) examined the association between IL28B polymorphism rs12979860 and the SVR rate in an African population, three (21,28,39) in an Asian population and 13 (4,10,17,27,29,(33)(34)(35)(36)(37)(38)41,42) in a European population. The SVR rate was highest in the Asian population (940/1,572), followed by the European population (1,904/3,412) and African population (100/452) (P<0.001).…”

Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

“…The presence of the interleukin-28B polymorphism was associated with a high SVR rate in the two studies which reported relevant data. 26,72 End-of-treatment responses were recorded in 49 studies. The pooled estimate of the proportion of patients who achieved an end-of-treatment response was higher: (i) for those who were HIV− than for those who were HIV+, at 74% versus 52%, respectively; (ii) for those who received ribavirin than for those who did not, at 69% versus 51%, respectively; and (iii) for those who received pegylated rather than standard interferon, at 73% versus 62%, respectively.…”

The pharmacogenetic background of hepatitis C treatment

“…In contrast, especially association of IL28B variants with HCV therapy failure have been repeatedly reported from several independent large cohorts band are therefore being considered as ''state of the art'' in HCV pharmacogenetics [16]. Moreover, IL28B genetics have been verified to apply to different ethnicities such as Caucasians [17] and Asians [18]. However, while IL28B rs12979860 was the most significant variant in Caucasians, African Americans and Hispanics [19], in Japanese it seems more likely to be the rs8099917 SNP, which was nevertheless also significant in the other cohorts [20].…”