维生素D缺乏是能够预测难治型丙肝不能成功获得SVR，维生素D结合蛋白基因多态性影响维生素D水平。本研究旨在评价慢性丙肝患者体内维生素D基线水平和维生素D结合蛋白基因多态性之间是否相互作用，二者在影响抗病毒反应作用中所占的比例。回顾分析206名丙肝患者，均给予聚乙二醇干扰素联合利巴韦林治疗。 测序了以下位点的基因多态性GC rs7041 G>T, GC rs4588 C>A, 和 IL-28B  rs12979860 C>T 。 GC rs7041 G>T 和 rs4588 C>A 的基因频率分别为G/G = 64 (31.1%), G/T = 100 (48.5%), T/T = 42 (20.4%) 和C/C = 108 (52.4%), C/A = 84 (40.8%), A/A = 14 (6.8%). 病人分为两类：携带超过3个主要等位基因为野生型，其他了非野生型。分为四组：VD≤20 ng/mL且为非野生型； VD≤20 ng/mL 且为野生型；VD>20 ng/mL且为非野生型；VD>20 ng/mL且为野生型。难治型丙肝获得SVR的比例从第一组到最后一组呈显著线性增加。多变量分析显示基线维生素D >20 ng/mL和维生素D结合蛋白基因野生型是预测SVR的独立因素。结论：正常血清维生素D水平和维生素D结合蛋白基因野生型对难治型丙肝给予聚乙二醇干扰素和利巴韦林抗病毒治疗获得SVR较强的预测作用。

吉林大学第一医院肝胆胰内科 王晓美 摘译

本文首次发表于[Hepatology, 2012, 56(5):1641-1650]

Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C

Vitamin D deficiency seems to predict the unsuccessful achievement of sustained viral response (SVR) after antiviral treatment in hepatitis C virus (HCV) difficult-to-treat genotypes. Vitamin D binding protein (GC) gene polymorphisms are known to influence vitamin D levels. This study was performed to assess whether the interaction between basal circulating vitamin D and the GC polymorphism plays a role in influencing the rate of antiviral responses in patients affected by chronic hepatitis C. In all, 206 HCV patients treated with a combination therapy of pegylated (PEG)-interferon plus ribavirin were retrospectively evaluated. GC rs7041 G>T, GC rs4588 C>A, and IL-28B rs12979860 C>T polymorphisms were genotyped. Frequencies of GC rs7041 G>T and rs4588 C>A polymorphisms were: G/G = 64 (31.1%), G/T = 100 (48.5%), T/T = 42 (20.4%) and C/C = 108 (52.4%), C/A = 84 (40.8%), A/A = 14 (6.8%). Patients were divided into those carrying ≥3 major alleles (wildtype [WT]+: G-C/G-C, G-C/T-C, G-C/G-A, N = 100) and the remaining (WT−: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N = 106). Four groups were identified: vitamin D ≤20 ng/mL and WT−, vitamin D ≤20 and WT+, vitamin D >20 and WT−, vitamin D >20 and WT+. In difficult-to-treat HCV genotypes the proportion of patients achieving SVR significantly increased with a linear trend from the first to the last group: 6/25 (24.0%), 9/24 (37.5%), 12/29 (41.4%), 19/29 (65.5%) (P = 0.003). At multivariate analysis, having basal vitamin D >20 ng/mL  plus the carriage of GC WT+ was found to be an independent predictor of SVR (odds ratio 4.52, P = 0.015). Conclusion: In difficult-to-treat HCV genotypes, simultaneous pretreatment normal serum vitamin D levels and the carriage of GC-globulin WT isoform strongly predicts the achievement of SVR after PEG-interferon plus ribavirin antiviral therapy. 点击下载此文件