Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C
Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C
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DOI：
10.3851/imp2100
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发表时间：
2012-01-01
影响因子：
1.2
通讯作者：
Craxi, Antonio
中科院分区：
文献类型：
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作者：
Petta, Salvatore;Ferraro, Donatella;Craxi, Antonio
背景：受IL28B状态、病毒载量、纤维化和胰岛素抵抗的影响，对聚乙二醇化干扰素(PEG化干扰素)和利巴韦林治疗取得快速病毒学应答(RVR)的1型慢性丙型肝炎(CHC)患者有较高的持续病毒学应答(SVR)机会。我们评估了血清25-羟基维生素D(25[OH]D)水平是否与RVR有关，是否可以与IL28B一起构建预测RVR的预处理模型。方法：对117例G1CHC患者进行活检、人体测量和代谢测量。用高效液相色谱法测定血清25(OH)D水平。同时对IL28B基因rs12979860和rs8099917的多态性进行了分析。所有患者均接受了聚乙二醇-干扰素-α2a联合利巴韦林的抗病毒治疗。结果：血清+/-SD25(OH)D平均水平为26.3+/-10.6mg/L(范围8.0~58.0)，31例(26.5%)患者存在rs12979860 CC多态。35例(29.9%)患者实现了RVR，其中32例(91.4%)有SVR，而82例未发生RVR的患者中有26例(31.7%)。多因素分析显示，rs12979860CC基因多态性(OR 4.575，95%CI 1.761，11.889；P=0.002)和较高的25(OH)D水平(OR 1.055，95%CI 1.010，1.101；P=1.101)是影响RVR发生的独立危险因素。结论：在G1型CHC患者中，血清25(OH)D水平和IL28B状态与发生RVR和SVR的可能性独立相关。当合并到治疗前预测模型中时，它们可以帮助进一步区分有很高可能性实现RVR和SVR的患者。
Background: Genotype 1 (G1) chronic hepatitis C (CHC) patients achieving a rapid virological response (RVR) on pegylated interferon (PEG-IFN) plus ribavirin have a high chance of sustained virological response (SVR), influenced by IL28B status, viral load, fibrosis and insulin resistance. We assessed whether 25-hydroxyvitamin D (25[OH] D) serum levels are linked to RVR and can be used together with IL28B to construct a pretreatment model to predict RVR.Methods: A total of 117 consecutive patients with G1 CHC were evaluated by biopsy and anthropometric and metabolic measurements. 25(OH) D serum levels were measured by HPLC. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated. All patients underwent antiviral therapy with PEG-IFN-alpha 2a plus ribavirin. HCV RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up.Results: Mean +/- SD 25(OH) D serum levels were 26.3 +/- 10.6 mu g/l (range 8.0-58.0) and 31 (26.5%) patients had the rs12979860 CC polymorphism. RVR was achieved in 35 (29.9%) patients, and 32 (91.4%) of them had an SVR, compared to 26 of 82 (31.7%) without RVR. The rs12979860 CC polymorphism (OR 4.575, 95% CI 1.761, 11.889; P=0.002) and higher 25(OH) D levels (OR 1.055, 95% CI 1.010, 1.101; P=0.01) were independently associated with the achievement of RVR by multivariate analysis. The likelihood of RVR progressively increased from patients in the worst class (vitamin D= 26.8 mu g/l and rs12979860 CC polymorphism; RVR 73.3%).Conclusions: In patients with G1 CHC, 25(OH) D serum levels and IL28B status are independently associated with the likelihood to achieve RVR and SVR. When incorporated into a pretreatment predictive model they can assist in further discriminating patients with a high likelihood of achieving RVR and SVR.