Association of IL28B Polymorphisms With the Response to Peginterferon Plus Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4

Abstract

Background: Three single nucleotide polymorphisms (SNPs) near interleukin-28B (IL-28B) gene were shown to be highly associated with treatment response (SVR) in patients with chronic hepatitis C virus (HCV) infection. There is limited data about the role of single and combined IL-28B polymorphisms in HCV-infected Polish population.

Objectives: This study's aim was to determine predictability of three IL-28B gene polymorphisms and other known prognostic factors on the treatment response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B polymorphisms on therapy was also compared with other known prognostic factors.

Patients and methods: We genotyped IL-28B polymorphisms (rs12979860, rs12980275 and rs8099917) by polymerase chain reaction-based restriction fragment length polymorphism assay in a group of 293 patients from which a selected cohort of 174 treatment-naiev patients underwent treatment.

Results: We showed that rs12979860 CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG, respectively. Patients bearing of IL-28B profile including the three favourable genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for IL-28B polymorphisms, there was no association of SVR with any other pretreatment clinical data in analyzed group. The correlation of SNPs with other host and viral factors revealed association of favorable genotypes of IL-28B markers with high levels of alanine aminotransferase and baseline HCV viral load.

Conclusions: IL-28B polymorphisms were the strongest pretreatment predictors of response to pegylated interferon and ribavirin in Polish patients chronically infected with HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than rs8099917 TT in predicting positive treatment response.

Keywords: Hepatitits C; Human; IL28B Protein; Interferon-alpha; Polymorphism; Single Nucleotide.

Figure 1.. The Association of IL-28B SNP With Baseline Viral Load in Chronic HCV Patients

There were significant differences in viral load between patients carrying CC and CT-TT rs12979860, TT and TG-GG rs8099917 and AA and AG-GG rs12980275 genotypes. Data are median with 10th, 25th, 75th and 90th percentiles as vertical boxes with error bars.

Figure 2.. The Association of IL-28B SNP With Baseline ALT Activity in Chronic HCV Patients

The ALT levels were significantly lower in patients carrying the unfavorable alleles (T of rs12979860, G of rs8099917 and G of rs12980275). Data are median with 10th, 25th, 75th and 90th percentiles as vertical boxes with error bars.