25-羟维生素D、铁蛋白与代谢相关脂肪性肝病及FIB-4指数的相关性分析

李文豪; 刘志平; 赵致维; 张金华

doi:10.3969/j.issn.1001-5256.2023.08.015

25-羟维生素D、铁蛋白与代谢相关脂肪性肝病及FIB-4指数的相关性分析

DOI: 10.3969/j.issn.1001-5256.2023.08.015

武汉市汉口医院消化内科, 武汉 430012

基金项目:

武汉市卫健委医学科研重点项目 (WX20A08)

伦理学声明：本研究方案于2021年3月5日经由武汉市汉口医院伦理委员会审批，批号：2020-HKYY017。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：刘志平负责研究的构思与设计，撰写论文；李文豪、赵致维负责数据收集与整理，统计学分析；张金华指导论文的撰写及内容的修改。

详细信息

通信作者:
刘志平，xiao6599@sina.com (ORCID：0000-0002-3447-0356)

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出版历程
- 收稿日期: 2022-11-12
- 录用日期: 2022-12-12
- 出版日期: 2023-08-20

Association of 25-hydro xyvitamin D and ferritin with metabolic associated fatty liver disease and fibrosis-4 index

Department of Gastroenterology, Wuhan Hankou Hospital, Wuhan 430012, China

Research funding:

Key Project of Wuhan Municipal Health Commission (WX20A08)

More Information

Corresponding author: LIU Zhiping, xiao6599@sina.com (ORCID: 0000-0002-3447-0356)

摘要

摘要: 目的探讨血清25-羟维生素D[25(OH)D]和铁蛋白(SF)水平与代谢相关脂肪性肝病(MAFLD)及FIB-4指数的相关性。方法回顾性分析2020年8月—2021年12月在武汉市汉口医院消化内科住院的595例患者临床资料。比较MAFLD患者(242例)与非MAFLD患者(353例)临床特征的差异。比较不同25(OH)D水平组MAFLD患病率及SF水平的差异。非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ²检验。采用Spearman相关性分析不同人群中血清25(OH)D与SF的相关性。采用二元Logistic回归分析25(OH)D和SF与MAFLD患病风险及FIB-4指数的关系。通过受试者工作特征曲线(ROC曲线)评估25(OH)D和SF预测MAFLD合并肝纤维化的诊断价值。结果与非MAFLD患者相比，MAFLD患者血清25(OH)D水平[15.35(11.26~20.02) vs 21.71(15.39~27.84)]明显降低，而SF水平[365.50(251.75~525.00) vs 205.00(112.50~275.00)]明显升高(Z值分别为-9.761、-13.317，P值均＜0.05)。随着血清25(OH)D水平的降低，MAFLD患病率呈升高趋势，SF水平亦呈升高趋势(Z=75.512，P＜0.05)。MAFLD患者中血清25(OH)D水平与SF存在显著负相关(r=-0.460，P＜0.05)。Logistic回归分析结果显示，血清25(OH)D降低(OR=0.934，95%CI：0.879~0.992，P=0.028)和SF升高(OR=1.009，95%CI：1.006~1.013，P＜0.001)是MAFLD的独立危险因素，而且25(OH)D降低还是MAFLD患者FIB-4指数升高(＞2.67)的独立危险因素(OR=0.852，95%CI：0.752~0.965，P=0.012)。ROC曲线分析显示，血清25(OH)D、SF及二者联合预测MAFLD患者FIB-4指数升高(＞2.67)的曲线下面积分别为0.793、0.829和0.851(P值均＜0.05)。结论血清25(OH)D与SF存在负相关，血清25(OH)D降低和SF升高与MAFLD患病风险及FIB-4指数升高相关，血清25(OH)D和SF水平对预测MAFLD患者合并肝纤维化具有一定的临床价值。
- 代谢相关脂肪性肝病 /
- 25-羟维生素D /
- 铁蛋白质类 /
- 肝纤维化
Abstract: Objective To investigate the association of serum 25-hydroxyvitamin D [25(OH)D] and serum ferritin (SF) with metabolic associated fatty liver disease (MAFLD) and fibrosis-4 (FIB-4) index. Methods A retrospective analysis was performed for the clinical data of 595 patients who were hospitalized in Department of Gastroenterology, Wuhan Hankou Hospital, from August 2020 to December 2021. Clinical features were compared between 242 patients with MAFLD and 353 patients without MAFLD, and the prevalence rate of MAFLD and SF level were compared between the groups with different 25(OH)D levels. The non-normally distributed continuous data were expressed as M(P₂₅-P₇₅), and the Mann-Whitney U test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to investigate the correlation between serum 25(OH)D and SF in different populations; a binary logistic regression analysis was used to investigate the association of 25(OH)D and SF with the risk of MAFLD and FIB-4 index; the receiver operating characteristic (ROC) curves were used to assess the value of 25(OH)D and SF in the diagnosis of liver fibrosis in patients with MAFLD. Results Compared with the non-MAFLD patients, the MAFLD patients had a significant reduction in serum 25(OH)D level [15.35(11.26-20.02) vs 21.71(15.39-27.84), Z=-9.761, P < 0.05] and a significant increase in SF level [365.50(251.75-525.00) vs 205.00(112.50-275.00), Z=-13.317, P < 0.05]. The prevalence rate of MAFLD and SF level tended to increase with the reduction in serum 25(OH)D level (Z=75.512, P < 0.05). Serum 25(OH)D level was significantly negatively correlated with SF in MAFLD patients (r=-0.460, P < 0.05). The logistic regression analysis showed that the reduction in serum 25(OH)D level (odds ratio [OR]=0.934, 95% confidence interval [CI]: 0.879-0.992, P=0.028) and the increase in SF level (OR=1.009, 95%CI: 1.006-1.013, P < 0.001) were independent risk factors for MAFLD, and the reduction in serum 25(OH)D level (OR=0.852, 95%CI: 0.752-0.965, P=0.012) was also an independent risk factor for elevated FIB-4 index (> 2.67) in MAFLD patients. The ROC curve analysis showed that serum 25(OH)D, SF, and their combination had an area under the ROC curve of 0.793, 0.829, and 0.851, respectively, in predicting elevated FIB-4 index (> 2.67) in MAFLD patients (all P < 0.05). Conclusion Serum 25(OH)D is negatively correlated with SF, and the reduction in serum 25(OH)D and the increase in SF are associated with the risk of MAFLD and elevated FIB-4 index. Serum 25(OH)D and SF levels have a certain value in predicting liver fibrosis in patients with MAFLD.
- Metabolic-Associated Fatty Liver Disease /
- 25-Hydroxyvitamin D /
- Ferritin /
- Hepatic Fibrosis

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图 1 血清25(OH)D水平与SF的相关性

注：a, 总体研究人群；b，MAFLD患者；c，男性；d，女性。

Figure 1. Correlation between serum 25 (OH) D level and SF

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图 2 25(OH)D和SF预测MAFLD合并FIB-4升高的ROC曲线

Figure 2. ROC curve of 25(OH)D and SF for predicting elevated FIB-4 in MAFLD patients

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表 1 MAFLD组和非MAFLD组临床特征比较

Table 1. Comparison of clinical characteristics between MAFLD and non-MAFLD group

指标	MAFLD组(n=242)	非MAFLD组(n=353)	统计值	P值
男/女(例)	164/78	185/168	χ²=13.969	＜0.001
年龄(岁)	51.00(40.00~59.25)	50.00(42.00~60.00)	Z=-0.405	0.685
2型糖尿病[例(%)]	80(33.1)	29(8.2)	χ²=59.216	＜0.001
高血压[例(%)]	107(44.2)	54(15.3)	χ²=60.829	＜0.001
BMI(kg/m²)	24.35(22.70~26.00)	21.20(19.80~22.80)	Z=-13.387	＜0.001
白细胞计数(×10⁹/L)	6.30(5.18~7.30)	6.40(5.00~8.10)	Z=-0.841	0.400
中性粒细胞(×10⁹/L)	3.70(2.98~4.73)	3.70(2.90~4.90)	Z=-0.361	0.718
淋巴细胞(×10⁹/L)	1.80(1.30~2.30)	2.00(1.50~2.40)	Z=-2.633	0.008
血小板(×10⁹/L)	210.00(170.75~248.75)	219.00(168.50~266.00)	Z=-1.060	0.289
ALT(U/L)	56.50(27.75~109.00)	26.00(14.00~35.00)	Z=-12.914	＜0.001
AST(U/L)	43.50(22.00~91.75)	24.00(13.50~34.00)	Z=-11.012	＜0.001
GGT(U/L)	65.50(37.00~122.00)	29.00(18.00~40.00)	Z=-12.311	＜0.001
BUN(mmol/L)	4.90(4.00~6.40)	4.90(3.80~6.20)	Z=-1.383	0.167
SCr(μmol/L)	68.50(57.75~85.00)	67.00(55.00~81.00)	Z=-2.072	0.038
SUA(μmol/L)	405.00(333.75~510.75)	321.00(255.50~361.00)	Z=-11.519	＜0.001
FPG(mmol/L)	5.71(4.89~7.23)	4.85(4.30~5.50)	Z=-9.368	＜0.001
TC(mmol/L)	4.85(4.04~5.74)	4.80(4.00~5.45)	Z=-1.810	0.070
TG(mmol/L)	1.93(1.30~2.90)	1.19(0.59~1.73)	Z=-11.597	＜0.001
HDL-C(mmol/L)	1.05(0.90~1.27)	1.30(1.20~1.52)	Z=-10.809	＜0.001
LDL-C(mmol/L)	2.84(2.07~3.45)	2.60(1.90~3.30)	Z=-2.611	0.009
CRP(mg/L)	2.50(1.32~5.22)	1.56(0.84~2.42)	Z=-7.857	＜0.001
25(OH)D(ng/mL)	15.35(11.26~20.02)	21.71(15.39~27.84)	Z=-9.761	＜0.001
SF(ng/mL)	365.50(251.75~525.00)	205.00(112.50~275.00)	Z=-13.317	＜0.001
注：CRP，C反应蛋白。

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表 2 不同25(OH)D水平组MAFLD患病率及SF水平比较

Table 2. Comparison of MAFLD prevalence and SF levels in different 25 (OH) D levels

组别	例数	MAFLD患病率[例(%)]	SF(ng/mL)
25(OH)D充足组	259	60 (23.2)	219.00(119.00~285.00)
25(OH)D不足组	233	109(46.8)	266.00(180.00~364.00)
25(OH)D缺乏组	103	73(70.9)	407.00(240.00~585.00)
统计值		χ²=75.433	Z=75.512
P值		＜0.001	＜0.001

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表 3 MAFLD患病风险的Logistic回归分析

Table 3. Logistic regression analysis of risk factors associated with MAFLD

变量	模型1		模型2		模型3
变量	OR(95%CI)	P值	OR(95%CI)	P值	OR(95%CI)	P值
25(OH)D	0.910(0.879~0.941)	＜0.001	0.911(0.872~0.952)	＜0.001	0.934(0.879~0.992)	0.028
SF	1.010(1.008~1.012)	＜0.001	1.010(1.008~1.013)	＜0.001	1.009(1.006~1.013)	＜0.001
注：模型1，未校正混杂因素；模型2，校正性别、年龄、BMI、2型糖尿病、高血压；模型3，在模型2基础上进一步校正SCr、SUA、FPG、TG、HDL-C、LDL-C、CRP等因素。

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表 4 MAFLD合并FIB-4升高的Logistic回归分析

Table 4. Logistic regression analysis of risk factors for elevated FIB-4 in MAFLD

变量	模型1		模型2		模型3
变量	OR(95%CI)	P值	OR(95%CI)	P值	OR(95%CI)	P值
25(OH)D	0.860(0.789~0.938)	0.001	0.874(0.801~0.955)	0.003	0.852(0.752~0.965)	0.012
SF	1.007(1.004~1.010)	＜0.001	1.007(1.004~1.010)	＜0.001	1.003(1.000~1.007)	0.074
注：模型1，未校正混杂因素；模型2，校正性别、年龄、BMI、2型糖尿病、高血压；模型3，在模型2基础上进一步校正ALT、AST、GGT、SUA、FPG等因素。

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