Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Internal Medicine, University of Florence, Florence, Italy.
J Viral Hepat. 2013 Apr;20(4):e107-14. doi: 10.1111/jvh.12017. Epub 2012 Dec 4.
HCV-related mixed cryoglobulinemia (MC) is characterized by clonal expansion of B cells producing a polyreactive natural antibody (rheumatoid factor) and interferon (IFN)-based therapy is the first therapeutic option in mild-moderate MC. Single nucleotide polymorphisms (SNPs) proximal to genes involved in the innate response (IL28B/IFN-λ gene family) are strongly associated with spontaneous and IFN-induced viral clearance in hepatitis C, but no data exist about their role in HCV-positive MC. A large cohort of patients with HCV and MC was studied to evaluate the influence of IL28B genotype on the response to treatment and/or the evolution to MC of HCV infection. The rs12979860/rs8099917 IL28B polymorphisms were analysed in 481 consecutive HCV-positive subjects (250 with MC and 231 without MC, as controls) using real-time PCR and direct sequencing. Hundred and fifteen HCV patients with MC received standard anti-HCV therapy, and the results were evaluated according to the IL28B SNP distribution. Similar IL28B SNPs allele frequencies were recorded for patients and controls. IL28B major allele homozygosis (for both SNPs tested) was tightly correlated with virological and clinical response (P = 0.002). A statistically significant association was limited to 'difficult-to-treat' (G1/4) HCV genotypes. The IL28B genotype was a strong independent predictor of response (P = 0.007, OR 6.06; CI 1.65-22.22). The IL28B genotype was confirmed to be a useful predictor of response to IFN-based therapy in patients with HCV and MC. The very close correlation between IL28B SNP distribution, virological and clinical response definitively confirmed the key role played by HCV in MC. Conversely, the IL28B genotype does not seem to influence the evolution to MC.
丙型肝炎相关混合性冷球蛋白血症（MC）的特征是产生多反应性天然抗体（类风湿因子）的 B 细胞克隆扩增，干扰素（IFN）为基础的治疗是轻度至中度 MC 的首选治疗方法。参与固有反应的基因（IL28B/IFN-λ 基因家族）附近的单核苷酸多态性（SNP）与丙型肝炎的自发性和 IFN 诱导的病毒清除密切相关，但尚无关于其在 HCV 阳性 MC 中作用的数据。研究了大量丙型肝炎和 MC 患者，以评估 IL28B 基因型对治疗反应和/或 HCV 感染向 MC 进展的影响。使用实时 PCR 和直接测序分析了 481 例连续的 HCV 阳性受试者（250 例 MC 和 231 例非 MC 作为对照）的 rs12979860/rs8099917 IL28B 多态性。115 例 MC 丙型肝炎患者接受了标准抗 HCV 治疗，并根据 IL28B SNP 分布评估结果。患者和对照的 IL28B 主要等位基因纯合子（两种测试的 SNP）与病毒学和临床反应密切相关（P = 0.002）。统计学显著关联仅限于“难治性”（G1/4）HCV 基因型。IL28B 基因型是反应的强独立预测因子（P = 0.007，OR 6.06；CI 1.65-22.22）。IL28B 基因型被证实可预测 HCV 和 MC 患者 IFN 为基础治疗的反应。IL28B SNP 分布、病毒学和临床反应之间的密切相关性明确证实了 HCV 在 MC 中的关键作用。相反，IL28B 基因型似乎不会影响向 MC 的进展。
