Division of Gastroenterology & Hepatology, University Hospital Zurich (USZ), Zurich, Switzerland.
Liver Int. 2012 Apr;32(4):635-43. doi: 10.1111/j.1478-3231.2011.02674.x. Epub 2011 Dec 8.
Decreased vitamin D levels have been described in various forms of chronic liver disease and associated with advanced fibrosis. Whether this association is a cause or consequence of advanced fibrosis remains unclear to date.
To analyse combined effects of 25-OH vitamin D plasma levels and vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate in HCV patients.
251 HCV patients underwent VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25-OH vitamin D levels were quantified in a subgroup of 97 patients without advanced fibrosis. The VDR haplotype and genotypes as well as plasma 25-OH vitamin D levels were associated with fibrosis progression.
The bAt[CCA]-haplotype was significantly associated with fibrosis progression >0.101 U/year (P = 0.007; OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty-five percent of bAt[CCA]-haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise, ApaI rs7975232 CC genotype was significantly associated with fibrosis progression and cirrhosis. Lower plasma 25-OH vitamin D levels were significantly associated with fibrosis progression >0.101 U/year in F0-2 patients (P = 0.013). Combined analysis of both variables revealed a highly significant additive effect on fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]-haplotype and 25-OH vitamin D < 20 μg/L compared with only 9.1% for the most favourable combination (P = 0.006). In multivariate analysis, the bAt-haplotype was an independent risk factor for fibrosis progression (P = 0.001; OR = 2.83).
Low 25-OH vitamin D plasma levels and the unfavourable VDR bAt[CCA]-haplotype are associated with rapid fibrosis progression in chronic HCV patients. In combination, both variables exert significant additive effects on fibrosis progression.
维生素 D 水平降低已在各种形式的慢性肝病中被描述，并与晚期纤维化相关。但这种关联是晚期纤维化的原因还是结果，目前尚不清楚。
分析 25-羟维生素 D 血浆水平和维生素 D 受体基因（VDR；NR1I1）多态性联合对 HCV 患者纤维化进展速度的影响。
251 例 HCV 患者进行了 VDR 基因分型（蝙蝠-单倍型：BsmI rs1544410 C、ApaI rs7975232 A 和 TaqI rs731236 A）。在没有晚期纤维化的 97 例患者亚组中定量检测了血浆 25-羟维生素 D 水平。VDR 单倍型和基因型以及血浆 25-羟维生素 D 水平与纤维化进展相关。
bAt[CCA]-单倍型与纤维化进展>0.101 U/年显著相关（P = 0.007；OR = 2.02）和肝硬化（P = 0.022；OR = 1.84）。45%的 bAt[CCA]-单倍型患者是快速纤维化者，21.1%为肝硬化患者。同样，ApaI rs7975232 CC 基因型与纤维化进展和肝硬化显著相关。在 F0-2 患者中，较低的血浆 25-羟维生素 D 水平与纤维化进展>0.101 U/年显著相关（P = 0.013）。两个变量的联合分析显示，bAt[CCA]-单倍型和 25-羟维生素 D < 20μg/L 的患者纤维化进展的相加效应非常显著，分别为 45.5%和 25-羟维生素 D < 20μg/L，而最有利的组合只有 9.1%（P = 0.006）。在多变量分析中，bAt 单倍型是纤维化进展的独立危险因素（P = 0.001；OR = 2.83）。
慢性 HCV 患者的低 25-羟维生素 D 血浆水平和不利的 VDR bAt[CCA]-单倍型与快速纤维化进展相关。这两个变量联合对纤维化进展有显著的相加作用。
