Background & Aims IL28B polymorphisms were shown to be strongly associated with the response to interferon therapy in chronic hepatitis C (CHC) and spontaneous viral clearance. However, little is known about how these polymorphisms affect the natural course of the disease. Thus, we conducted the present meta-analysis to assess the impact of IL28B polymorphisms on disease progression. Methods A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library. Integrated odds ratios (OR) were calculated with a fixed-effects or random-effects model based on heterogeneity analyses. Results We identified 28 studies that included 10,024 patients. The pooled results indicated that the rs12979860 genotype CC was significantly associated (vs. genotype CT/TT; OR, 1.122; 95%CI, 1.003–1.254; P = 0.044), and that the rs8099917 genotype TT tended to be (vs. genotype TG/GG; OR, 1.126; 95%CI, 0.988–1.284; P = 0.076) associated, with an increased possibility of severe fibrosis. Both rs12979860 CC (vs. CT/TT; OR, 1.288; 95%CI, 1.050–1.581; P = 0.015) and rs8099917 TT (vs. TG/GG; OR, 1.324; 95%CI, 1.110–1.579; P = 0.002) were significantly associated with a higher possibility of severe inflammation activity. Rs8099917 TT was also significantly associated with a lower possibility of severe steatosis (vs. TG/GG; OR, 0.580; 95%CI, 0.351–0.959; P = 0.034), whereas rs12979860 CC was not associated with hepatic steatosis (vs. CT/TT; OR, 1.062; 95%CI, 0.415–2.717; P = 0.901). Conclusions IL28B polymorphisms appeared to modify the natural course of disease in patients with CHC. Disease progression seems to be promoted in patients with the rs12979860 CC and rs8099917 TT genotypes.
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