Petta Salvatore, Ferraro Donatella, Cammà Calogero, Cabibi Daniela, Di Cristina Antonietta, Di Marco Vito, Di Stefano Rosa, Grimaudo Stefania, Mazzola Alessandra, Levrero Massimo, Scazzone Concetta, Craxì Antonio
Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy.
Antivir Ther. 2012;17(5):823-31. doi: 10.3851/IMP2100. Epub 2012 Apr 13.
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.
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-α2a plus ribavirin. HCV RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up.
Mean ±SD 25(OH)D serum levels were 26.3 ±10.6 μg/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 μg/l and TT/TC polymorphism; RVR 14.2%), to those with only one positive predictor (RVR 29.7% and 37.5%), and to those in the best class (vitamin D≥26.8 μg/l and rs12979860 CC polymorphism; RVR 73.3%).
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.
基因型1（G1）慢性丙型肝炎（CHC）患者在接受聚乙二醇干扰素（PEG-IFN）联合利巴韦林治疗时获得快速病毒学应答（RVR），其持续病毒学应答（SVR）几率较高，受白细胞介素28B（IL28B）状态、病毒载量、纤维化及胰岛素抵抗影响。我们评估了25-羟维生素D（25[OH]D）血清水平是否与RVR相关，以及能否与IL28B一起用于构建预测RVR的治疗前模型。
通过活检以及人体测量和代谢指标测定，对117例连续的G1 CHC患者进行评估。采用高效液相色谱法测定25(OH)D血清水平。同时评估IL28B rs12979860和rs8099917基因多态性。所有患者均接受PEG-IFN-α2a联合利巴韦林抗病毒治疗。在基线、第4周、第12周、治疗结束时及随访6个月后评估丙型肝炎病毒（HCV）RNA。
25(OH)D血清平均水平±标准差为26.3±10.6μg/l（范围8.0 - 58.0），31例（26.5%）患者存在rs12979860 CC基因多态性。35例（29.9%）患者获得RVR，其中32例（91.4%）实现SVR，而未获得RVR的82例患者中有26例（31.7%）实现SVR。多因素分析显示，rs12979860 CC基因多态性（比值比[OR] 4.575，95%置信区间[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 = 0.01）与获得RVR独立相关。从最差组（维生素D<26.8μg/l且为TT/TC基因多态性；RVR为14.2%）患者，到仅有一个阳性预测指标的患者（RVR分别为29.7%和37.5%），再到最佳组（维生素D≥26.8μg/l且rs12979860 CC基因多态性；RVR为73.3%）患者，RVR的可能性逐渐增加。
在G1 CHC患者中，25(OH)D血清水平和IL28B状态与获得RVR和SVR的可能性独立相关。纳入治疗前预测模型时，它们有助于进一步区分有较高可能性获得RVR和SVR的患者。
