脂溶性维生素水平与胆汁淤积性肝病患儿生化指标的相关性分析

李婧; 夏婧; 吴捷

doi:10.3969/j.issn.1001-5256.2021.10.023

脂溶性维生素水平与胆汁淤积性肝病患儿生化指标的相关性分析

DOI: 10.3969/j.issn.1001-5256.2021.10.023

李婧¹,
夏婧¹,
吴捷^{1, 2, ,}

1.
中国医科大学附属盛京医院小儿消化内科，沈阳 110004
2.
首都医科大学附属北京儿童医院消化科，北京 100045

详细信息

通信作者:
吴捷，wujiedoc@163.com

中图分类号: R575
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出版历程
- 收稿日期: 2021-02-21
- 录用日期: 2021-03-15
- 出版日期: 2021-10-20

Correlation of the levels of fat-soluble vitamins with biochemical parameters in infants with cholestatic liver disease

Jing LI¹,
Jing XIA¹,
Jie WU^{1, 2
, ,}

1.
Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
2.
Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China

摘要

摘要: 目的研究脂溶性维生素(FSVs)水平与婴儿胆汁淤积性肝病相关指标变化的关系，同时为胆汁淤积患儿FSVs补充治疗提供依据。方法选取2018年1月—2020年12月于中国医科大学附属盛京医院小儿消化内科住院治疗的胆汁淤积性肝病患儿136例为观察组，同期就诊于本院的健康体检婴儿30例为对照组，记录患儿胎龄、日龄、性别、病因等，完善肝功能、血清钙、血清磷、凝血功能、病原学、影像学和基因检查。同时测定血清维生素A、D、E、K水平。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。结果观察组与对照组之间FSVs水平差异有统计学意义(维生素A：Z=-2.850，P=0.004；维生素D3：Z=-5.705，P＜0.001；维生素E：Z=-5.894，P＜0.001；维生素K：Z=-2.482，P=0.013)；足月儿与早产儿之间FSVs水平无显著差异(P值均＞0.05)。血清TBil与维生素A、D3具有显著相关性(维生素A：r=-0.178，P=0.038；维生素D3：r=-0.296，P＜0.001)，血清DBil(r=-0.328，P＜0.001)、TBA(r=-0.194，P=0.023)水平与维生素D3具有显著相关性；血清ALP与维生素A、D3具有显著相关性(维生素A：r=-0.282，P=0.001；维生素D3：r=-0.514，P＜0.001)。血清维生素D3水平与血清钙(r=0.303，P＜0.001)、磷(r=0.310，P＜0.001)呈正相关，与ALP水平呈负相关(r=-0.514，P＜0.001)。血清维生素K水平与凝血指标无显著相关性(P值均＞0.05)。接受维生素K治疗和未接受维生素K治疗患儿维生素K水平存在统计学意义(Z=-5.662，P＜0.001)。结论胆汁淤积患儿FSVs水平明显低于同日龄健康婴儿。血清TBil升高对维生素A、D3缺乏有提示作用; 血清DBil、TBA水平升高对维生素D3缺乏有提示作用；血清ALP升高可提示维生素A、D3缺乏。
- 胆汁淤积 /
- 维生素类 /
- 婴儿
Abstract: Objective To investigate the correlation of the levels of fat-soluble vitamins (FSVs) with the changes of related indicators in infants with cholestatic liver disease, and to provide a basis for the supplementation of FSVs in infants with cholestatic liver disease. Methods A total of 136 children with cholestatic liver disease who were hospitalized in Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, from January 2018 to December 2020 were enrolled as observation group, and 30 healthy infants who underwent physical examination in our hospital during the same period of time were enrolled as control group. Related data were recorded, including gestational age, age in days, sex, and etiology, and related examinations were performed, including liver function, serum calcium, serum phosphorus, coagulation function, etiology, radiological examination, and gene detection. The serum levels of vitamins A, D, E, and K were also measured. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. Results There were significant differences in the levels of FSVs between the observation group and the control group (vitamin A: Z=-2.850, P= 0.004; vitamin D3: Z=-5.705, P < 0.001; vitamin E: Z=-5.894, P < 0.001; vitamin K: Z=-2.482, P= 0.013), and there were no significant differences in the levels of FSVs between the full-term infants and the preterm infants (all P > 0.05). Serum total bilirubin was significantly correlated with vitamins A and D3 (vitamin A: r=-0.178, P=0.038; vitamin D3: r=-0.296, P < 0.001), and serum direct bilirubin and total bile acid were significantly correlated with vitamin D3 (r=-0.328 and -0.194, both P < 0.05); serum alkaline phosphatase was significantly correlated with vitamins A and D3 (vitamin A: r=-0.282, P= 0.001; vitamin D3: r=-0.514, P < 0.001). Serum vitamin D3 level was positively correlated with serum calcium (r=0.303, P < 0.001) and phosphorus (r=0.310, P < 0.001) and was negatively correlated with alkaline phosphatase (r=-0.514, P < 0.001). There was no significant correlation between serum vitamin K level and coagulation markers (all P > 0.05), while there was a significant change in vitamin K level after treatment (Z=-5.662, P < 0.001). Conclusion The levels of FSVs in children with cholestatic liver disease are significantly lower than those in healthy infants of the same age in days. An increase in serum total bilirubin can indicate the deficiency of vitamins A and D3; increases in serum direct bilirubin and total bile acid can indicate vitamin D3 deficiency; an increase in serum alkaline phosphatase can indicate the deficiency of vitamins A and D3.
- Cholestasis /
- Vitamins /
- Infant

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表 1 两组婴儿FSVs水平比较

组别	例数	维生素A(ng/mL)	维生素D2(ng/mL)	维生素D3(ng/mL)	维生素E(μg/mL)	维生素K(ng/mL)
观察组	136	160.40(105.75~302.43)	1.06(0.50~2.57)	7.70(4.03~21.40)	6.00(2.94~8.51)	1.05(0.23~3.10)
对照组	30	213.00(146.39~354.92)	0.92(0.52~2.30)	29.81(15.21~41.79)	11.06(8.55~16.48)	7.69(0.55~276.71)
Z值		-2.850	-0.535	-5.705	-5.894	-2.482
P值		0.004	0.593	＜0.001	＜0.001	0.013

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表 2 足月与早产ICH患儿间FSVs水平比较

组别	例数	维生素A(ng/mL)	维生素D2(ng/mL)	维生素D3(ng/mL)	维生素E(μg/mL)	维生素K(ng/mL)
足月	111	159.74(114.75~230.04)	0.82(0.28~1.75)	5.86(2.88~11.64)	5.43(3.53~7.35)	92.53(6.15~300.37)
早产	25	163.95(11.27~211.22)	1.42(0.63~2.73)	8.26(4.36~15.53)	4.61(1.50~10.02)	8.27(1.32~357.32)
Z值		-0.464	-1.652	-1.517	-1.160	-1.587
P值		0.643	0.099	0.129	0.246	0.112

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表 3 胆汁淤积相关指标与FSVs水平的相关性

指标	统计值	维生素A(ng/mL)	维生素D3(ng/mL)	维生素E(μg/mL)	维生素K(ng/mL)
GGT(U/L)	r值	-0.067	-0.108	0.021	-0.012
	P值	0.437	0.212	0.812	0.887
TBil(μmol/L)	r值	-0.178	-0.296	-0.023	0.004
	P值	0.038	＜0.001	0.794	0.966
DBil(μmol/L)	r值	-0.100	-0.328	-0.012	0.021
	P值	0.245	＜0.001	0.892	0.808
TBA(μmol/L)	r值	-0.093	-0.194	0.054	0.146
	P值	0.282	0.023	0.529	0.090
ALP(U/L)	r值	-0.282	-0.514	-0.146	0.155
	P值	0.001	＜0.001	0.089	0.072

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参考文献(15)

[1]	FAWAZ R, BAUMANN U, EKONG U, et al. Guideline for the evaluation of cholestatic jaundice in infants: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition[J]. J Pediatr Gastroenterol Nutr, 2017, 64(1): 154-168. DOI: 10.1097/MPG.0000000000001334.
[2]	CHEN HL, WU SH, HSU SH, et al. Jaundice revisited: Recent advances in the diagnosis and treatment of inherited cholestatic liver diseases[J]. J Biomed Sci, 2018, 25(1): 75. DOI: 10.1186/s12929-018-0475-8.
[3]	GONCALVES A, ROI S, NOWICKI M, et al. Fat-soluble vitamin intestinal absorption: Absorption sites in the intestine and interactions for absorption[J]. Food Chem, 2015, 172: 155-160. DOI: 10.1016/j.foodchem.2014.09.021.
[4]	YEUNG CY. Fat-soluble vitamin deficiency in pediatric patients with chronic liver disease[J]. Pediatr Neonatol, 2019, 60(1): 1-2. DOI: 10.1016/j.pedneo.2019.01.003.
[5]	SHEN YM, WU JF, HSU HY, et al. Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis[J]. J Pediatr Gastroenterol Nutr, 2012, 55(5): 587-591. DOI: 10.1097/MPG.0b013e31825c9732.
[6]	MOREIRA-SILVA H, MAIO I, BANDEIRA A, et al. Metabolic liver diseases presenting with neonatal cholestasis: At the crossroad between old and new paradigms[J]. Eur J Pediatr, 2019, 178(4): 515-523. DOI: 10.1007/s00431-019-03328-5.
[7]	OKANO Y, OHURA T, SAKAMOTO O, et al. Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2[J]. Mol Genet Metab, 2019, 127(3): 175-183. DOI: 10.1016/j.ymgme.2019.06.004.
[8]	ABDEL-RAHMAN N, SHARAWY MH, MEGAHED N, et al. Vitamin D3 abates BDL-induced cholestasis and fibrosis in rats via regulating Hedgehog pathway[J]. Toxicol Appl Pharmacol, 2019, 380: 114697. DOI: 10.1016/j.taap.2019.114697.
[9]	MARCHILI MR, SANTORO E, MARCHESI A, et al. Vitamin K deficiency: A case report and review of current guidelines[J]. Ital J Pediatr, 2018, 44(1): 36. DOI: 10.1186/s13052-018-0474-0.
[10]	AKIYAMA H, OKAMURA Y, NAGASHIMA T, et al. Intracranial hemorrhage and vitamin K deficiency associated with biliary atresia: Summary of 15 cases and review of the literature[J]. Pediatr Neurosurg, 2006, 42(6): 362-367. DOI: 10.1159/000095566.
[11]	LEVY DS, GREWAL R, LE TH. Vitamin K deficiency: An emerging player in the pathogenesis of vascular calcification and an iatrogenic consequence of therapies in advanced renal disease[J]. Am J Physiol Renal Physiol, 2020, 319(4): f618-f623. DOI: 10.1152/ajprenal.00278.2020.
[12]	FREUND C, GOTTHARDT DN. Vitamin A deficiency in chronic cholestatic liver disease: Is vitamin A therapy beneficial?[J]. Liver Int, 2017, 37(12): 1752-1758. DOI: 10.1111/liv.13433.
[13]	ULATOWSKI LM, MANOR D. Vitamin E and neurodegeneration[J]. Neurobiol Dis, 2015, 84: 78-83. DOI: 10.1016/j.nbd.2015.04.002.
[14]	DONG R, SUN S, LIU XZ, et al. Fat-soluble vitamin deficiency in pediatric patients with biliary atresia[J]. Gastroenterol Res Pract, 2017, 2017: 7496860. DOI: 10.1155/2017/7496860.
[15]	VENKAT VL, SHNEIDER BL, MAGEE JC, et al. Total serum bilirubin predicts fat-soluble vitamin deficiency better than serum bile acids in infants with biliary atresia[J]. J Pediatr Gastroenterol Nutr, 2014, 59(6): 702-707. DOI: 10.1097/MPG.0000000000000547.