维生素 D 血清水平低与基因型 1 慢性丙型肝炎的严重纤维化和对基于干扰素治疗的低反应性有关。

Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C.

机构信息

Cattedra ed Unità Operativa di Gastroenterologia, DiBiMIS, University of Palermo, Italy.

出版信息

Hepatology. 2010 Apr;51(4):1158-67. doi: 10.1002/hep.23489.

DOI:10.1002/hep.23489

PMID:20162613

Abstract

UNLABELLED

25-Hydroxyvitamin D (25[OH]D) can potentially interfere with inflammatory response and fibrogenesis. Its role in disease progression in chronic hepatitis C (CHC) and its relation with histological and sustained virological response (SVR) to therapy are unknown. One hundred ninety-seven patients with biopsy-proven genotype 1 (G1) CHC and 49 healthy subjects matched by age and sex were consecutively evaluated. One hundred sixty-seven patients underwent antiviral therapy with pegylated interferon plus ribavirin. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. Tissue expression of cytochrome (CY) P27A1 and CYP2R1, liver 25-hydroxylating enzymes, were assessed by immunochemistry in 34 patients with CHC, and in eight controls. The 25(OH)D serum levels were significantly lower in CHC than in controls (25.07 +/- 9.92 microg/L versus 43.06 +/- 10.19; P < 0.001). Lower levels of 25(OH)D were independently linked to female sex (P = 0.007) and necroinflammation (P = 0.04) by linear regression analysis. CYP27A1, but not CYP2R1, was directly related to 25(OH)D levels (P = 0.01), and inversely to necroinflammation (P = 0.01). Low 25(OH)D (odds ratio [OR], 0.942; 95% confidence interval [CI], 0.893-0.994) and cholesterol (OR, 0.981; 95%CI, 0.969-0.992) levels, older age (OR, 1.043; 95%CI, 1.002-1.085), high ferritin (OR, 1.003; 95%CI, 1.001-1.005), and necroinflammation (OR, 2.235; 95%CI, 1.014-4.929) were independently associated with severe fibrosis (F3-F4) by multivariate logistic analysis. Seventy patients (41%) achieved SVR. By multivariate analysis, hepatic steatosis (OR, 0.971; 95%CI, 0.944-0.999), lower cholesterol (OR, 1.009; 95% CI, 1.000-1.018), and 25(OH)D levels (OR, 1.039; 95%CI, 1.002-1.077) were independently associated with no SVR.

CONCLUSION

G1 CHC patients had low 25(OH)D serum levels, possibly because of reduced CYP27A1 expression. Low vitamin D is linked to severe fibrosis and low SVR on interferon (IFN)-based therapy.

摘要

未加标签

25-羟维生素 D（25[OH]D）可能会干扰炎症反应和纤维化。其在慢性丙型肝炎（CHC）疾病进展中的作用及其与组织学和持续病毒学应答（SVR）的关系尚不清楚。197 名经活检证实为基因型 1（G1）CHC 且年龄和性别相匹配的 49 名健康受试者被连续评估。167 名患者接受聚乙二醇干扰素加利巴韦林的抗病毒治疗。通过高压液相色谱法测量血清 25（OH）D 水平。在 34 名 CHC 患者和 8 名对照中，通过免疫化学评估细胞色素（CY）P27A1 和 CYP2R1 的组织表达，肝 25-羟化酶。CHC 患者的血清 25（OH）D 水平明显低于对照组（25.07±9.92μg/L比 43.06±10.19；P<0.001）。线性回归分析表明，较低的 25（OH）D 水平与女性（P=0.007）和坏死性炎症（P=0.04）独立相关。CYP27A1 而不是 CYP2R1 与 25（OH）D 水平直接相关（P=0.01），与坏死性炎症呈负相关（P=0.01）。低 25（OH）D（比值比[OR]，0.942；95%置信区间[CI]，0.893-0.994）和胆固醇（OR，0.981；95%CI，0.969-0.992）水平、年龄较大（OR，1.043；95%CI，1.002-1.085）、铁蛋白高（OR，1.003；95%CI，1.001-1.005）和坏死性炎症（OR，2.235；95%CI，1.014-4.929）与多变量逻辑分析中的严重纤维化（F3-F4）独立相关。70 名患者（41%）获得 SVR。通过多变量分析，肝脂肪变性（OR，0.971；95%CI，0.944-0.999）、胆固醇降低（OR，1.009；95%CI，1.000-1.018）和 25（OH）D 水平（OR，1.039；95%CI，1.002-1.077）与无 SVR 独立相关。