Low Vitamin D Serum Level Is Related to Severe Fibrosis and Low Responsiveness to Interferon-Based Therapy in Genotype 1 Chronic Hepatitis C
Low Vitamin D Serum Level Is Related to Severe Fibrosis and Low Responsiveness to Interferon-Based Therapy in Genotype 1 Chronic Hepatitis C
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DOI：
10.1002/hep.23489
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发表时间：
2010-04-01
期刊：
影响因子：
13.5
通讯作者：
Craxi, Antonio
中科院分区：
文献类型：
--
作者：
Petta, Salvatore;Camma, Calogero;Craxi, Antonio
25-羟基维生素D(25[OH]D)可潜在地干扰炎症反应和纤维化形成。它在慢性丙型肝炎(CHC)疾病进展中的作用及其与组织学和治疗后持续病毒学应答(SVR)的关系尚不清楚。197名经活检证实为1型(G1)慢性丙型肝炎的患者和49名年龄和性别匹配的健康受试者被连续评估。167例患者接受了聚乙二醇化干扰素联合利巴韦林的抗病毒治疗。用高压液相色谱仪测定血清25(OH)D水平。应用免疫组织化学方法检测34例慢性丙型肝炎患者和8例正常对照肝组织中细胞色素P27A1和细胞色素P27A1和细胞色素P27R1的表达。慢性丙型肝炎患者血清25(OH)D水平显著低于对照组(25.07+/-9.92mU/L比43.06/-10.19；P<；0.001)。线性回归分析显示，25(OH)D水平降低与女性(P=0.007.0 5)和坏死性炎症(P=0.0 4)独立相关。CYP27A1与25(OH)D水平呈正相关(P=0.01)，与坏死性炎症呈负相关(P=0.01)。低25(OH)D(优势比[OR]0.942；95%可信区间[CI]，0.893-0.994)和胆固醇(OR，0.981；95%CI，0.969-0.992)水平，老年(OR，1.043；95%CI，1.002-1.085)，高铁蛋白(OR，1.003；95%CI，1.001-1.005)，以及坏死性炎症(OR，2.235；多因素Logistic分析显示，95%可信区间(1.014-4.929)与重度纤维化(F3-F4)独立相关。70例患者(41%)实现了SVR。多因素分析显示，肝脏脂肪变性(OR，0.971；95%CI，0.944~0.999)、低胆固醇(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。结论：G1期CHC患者血清25(OH)D水平较低，可能与细胞色素P27A1表达降低有关。低维生素D与严重纤维化和基于干扰素的低SVR治疗有关。(《肝病》2010；51：1158-1167。)
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 mu g/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. (HEPATOLOGY 2010; 51:1158-1167.)