The effects of interleukin-28B gene polymorphisms on antiviral treatment response in patients with chronic hepatitis C

Abstract

Objective To investigate the relationship between interleukin (IL)-28B gene polymorphisms (rs12979860 and rs8099917) and treatment response in patients with chronic hepatitis C in China. Methods Taqman probes single nucleotide polymorphism genotyping methods were used to detect the genotypes of rs12979860 (C/T) and rs8099917 (T/G) located at IL-28B gene in 105 included patients. The patients were treated with standard doses of pegylated interferon plus ribavirin and were followed up regularly for therapeutic response and adverse reaction. The relationship between IL-28B gene polymorphism and antiviral treatment response of patients were analyzed. Categorical data were analyzed using Pearson chi-square test or Fisher exact test. Results Totally 105 cases were included in our study and 2 cases lost to follow-up because of moving away. Eight-one cases (78.6%) of the remaining 103 patients were CC/TT genotype (CC/TT group) at rs12979860 and rs8099917, 19 cases (18.4%) were CT/TG (CT/TG group) and 3 cases (2.9%)were TT/TG (TT/TG group). No other genotypes were detected and linkage disequilibrium was discovered at the two polymorphism loci (r2=0.11). After 4 weeks of treatment, 35 cases (43.2%) in CC/TT group, 3 cases (15.8%) in CT/TG group and non in TT/TG group achieved rapid virological response (RVR). There were statistically significant differences among three groups (P=0.033). After 12 weeks of treatment, 45 cases (55.6%) in CC/TT group, 6 cases (31.6%) in CT/TG group and none in TT/TG group achieved early virological response (EVR). There were statistically significant differences among three groups (P=0.025). At the end of the treatment, 68 cases (83.9%) in CC/TT group, 10 cases (52.6%) in CT/TG group and only 1 case (33.3%) in TT/TG group achieved end-of-treatment response (ETR). There were significant statistical differences among the three groups (P=0.003). After 24 weeks of follow-up, 62 cases (76.5%) in CC/TT group, 9 cases (47.4%) in CT/TG group and 1 case (33.3%) in TT/TG group achieved sustained virological response (SVR). There were statistically significant differences among the three groups (P=0.014). One hundred and one cases in CC/TT group developed adverse events, among them 19 cases needed clinical treatment. There were 43 cases in CT/TG group developed adverse events and 9 cases needed treatment. Seven cases in TT/TG group developed adverse events and only 1 case needed treatment. There were no statistically significant difference among three groups (χ2=0.139, P>0.05). Conclusions The genotype of rs12979860 (C/T) and rs8099917 (T/G) at IL-28B gene could affect the treatment response in patients with chronic hepatitis C. RVR and SVR are higher in patients with genotype CC/TT, which might help to guide HCV treatment. Key words: Interleukin-28B; Hepatitis C, chronic; Polymorphism, single nucleotide; Antiviral response