Combined Effects of 2 Interleukin 28B Polymorphisms on the Therapeutic Outcome of Hepatitis C Patients with Circulating Cryoglobulins

Chronic hepatitis C is commonly associated with extrahepatic manifestations. Cryoglobulins are observed in 40% to 60% of such patients and their presence seems to modify response to therapy. The new antivirals are greatly improving the sustained virological response (SVR); however, their high cost limits the use, leaving pegylated interferon plus ribavirin (PR) still the standard-of-care therapy worldwide. Since PR therapy is burdened with several side effects, pretreatment predictions of patients who are unlikely to respond to this regimen may avoid ineffective treatment. Variants of the interleukin-28B (IL28B) gene correlate with an SVR to PR, and combined IL28B polymorphisms may improve the prediction of treatment outcome. The potential role of both rs8099917 and rs12979860 IL28B single nucleotide polymorphisms (SNPs) combined with presence of cryoglobulins in predicting SVR to PR in hepatitis C virus (HCV)-chronically infected patients was analyzed in the present study. Single and combined IL28B SNPs (rs12979860 and rs8099917) were analyzed in 64 chronic HCV patients treated with PR showing circulating cryoglobulins and compared to 108 noncryoglobulinemic subjects to verify the predictive value on the SVR. The association of rs12979860CC or rs8099917TT with SVR was confirmed in the noncryoglobulinemic group but not in cryoglobulinemic patients. Moreover, the combined determination of both SNPs improved the prediction of SVR in noncryoglobulinemic patients but not in the cryoglobulinemic subgroup. We report that both single and combined determination of IL28B rs12979860 and rs8099917 SNPs in chronic HCV patients with circulating cryoglobulins treated with PR may have a reduced predictive value of SVR.