血清25-羟维生素D、纤维化分期、遗传易感性与严重肝脏疾病风险之间的关系。
Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease.
作者信息
Zhou Chun, Zhang Yanjun, Ye Ziliang, He Panpan, Zhang Yuanyuan, Gan Xiaoqin, Yang Sisi, Liu Mengyi, Wu Qimeng, Qin Xianhui
机构信息
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China.
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China.
出版信息
Nutrition. 2024 Mar;119:112320. doi: 10.1016/j.nut.2023.112320. Epub 2023 Dec 1.
OBJECTIVES
The prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association.
METHODS
The study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death.
RESULTS
During a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84-0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; P < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (P = 0.216).
CONCLUSIONS
Lower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.
目的
维生素D与新发严重肝病之间的前瞻性关联仍不明确。本研究的目的是评估血清25-羟维生素D（25(OH)D）与新发严重肝病的关联，并评估通过纤维化4（FIB-4）评分评估的纤维化阶段和肝硬化的遗传风险是否会改变这种关联。
方法
该研究纳入了英国生物银行中439807名基线时无肝病的参与者。使用化学发光免疫分析法测量血清25(OH)D浓度。主要结局是新发严重肝病，这是一个包括代偿期或失代偿期肝硬化、肝衰竭、肝细胞癌和肝病相关死亡的综合定义。
结果
在中位随访12年期间，4510名参与者发生了新发严重肝病。总体而言，血清25(OH)D与新发严重肝病呈负相关（每标准差增加，调整后的风险比[HR]为0.87；95%置信区间为0.84-至0.91）。同样，血清25(OH)D（每标准差增加）分别与新发代偿期肝硬化、失代偿期肝硬化、肝衰竭和肝病相关死亡显著负相关，HR范围为0.75至0.87。未发现与肝细胞癌有显著关联。此外，在FIB-4评分较高的人群（≥2.67、1.3至<2.67以及<1.3；P<0.001）中，血清25(OH)D与严重肝病之间的负相关更强。然而，使用12个相关单核苷酸多态性计算的肝硬化遗传风险并未显著改变血清25(OH)D与严重肝病之间的关联（P = 0.216）。
结论
较低的血清25(OH)D浓度与新发严重肝病的风险增加显著相关，尤其是在FIB-4评分较高的参与者中。
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