肝硬化患者中与维生素D相关的免疫调节

StephenW

Vitamin D-related immunomodulation in patients with liver cirrhosis

Triantos, Christosa; Kalafateli, Mariaa; Aggeletopoulou, Ioannaa,,b; Diamantopoulou, Georgiaa; Spantidea, Panagiota I.b; Michalaki, Marinac; Vourli, Georgiad; Konstantakis, Christosa; Assimakopoulos, Stelios F.e; Manolakopoulos, Spiliosf; Gogos, Charalambose; Kyriazopoulou, Venetsanac; Mouzaki, Athanasiab; Thomopoulos, KonstantinosaAuthor Information

Divisions of aGastroenterology

bHematology

cEndocrinology, Diabetes and Metabolic Diseases, Department of Internal Medicine, University Hospital of Patras, Patras

dDepartment of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens

eDepartment of Internal Medicine, University Hospital of Patras, Patras

fSecond Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece

Received 29 July 2019 Accepted 24 September 2019

Correspondence to Christos Triantos, MD, FAASLD, D. Stamatopoulou 4, Rio 26504, Patras, Greece, Tel: +306972894651; fax: +302610625382; e-mail: [email protected]
European Journal of Gastroenterology & Hepatology: July 2020 - Volume 32 - Issue 7 - p 867-876
doi: 10.1097/MEG.0000000000001597

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Abstract
Objective(s)

Increasing evidence indicates that vitamin D status is linked to severity of liver cirrhosis and patients’ survival. However, the potential role of vitamin D-related immunomodulation in hepatic decompensation and patients’ mortality in relation to vitamin D deficiency remains unknown. The aim of the current study is to evaluate the association between vitamin D status and vitamin D binding protein (VDBP) levels with serum cytokine and lipopolysaccharide binding protein (LBP) and to examine their role on disease severity and cirrhotics’ mortality.
Methods

One hundred consecutive Caucasian patients with liver cirrhosis were enrolled in the study. 25(OH)D, VDBP, and LBP concentrations were assessed by ELISA. Cytokine tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), IL-1β, IL-8, IL-10, and IL-12 levels were determined by Cytometric Bead Array.
Results

25(OH)D levels were inversely correlated with CP score, MELD, IL-6, and CP stage and VDBP levels with CP score, MELD, IL-6, IL-8, LBP, and CP stage. Cirrhotics with 25(OH)D deficiency and severe deficiency had significantly higher CP score, increased IL-6 levels and lower VDBP levels. In the multivariate analysis, the independent prognostic factors associated with patients’ survival were CP stage B [hazard ratio = 6.75; 95% confidence interval (CI) 1.32, 34.43; P = 0.022], CP stage C (hazard ratio = 7.39; 95% CI 1.41, 38.81; P = 0.018), the presence of hepatocellular carcinoma (hazard ratio = 4.50; 95% CI 1.54, 13.13; P = 0.006) and 25(OH)D levels (hazard ratio = 0.87; 95% CI 0.80, 0.95; P = 0.002).
Conclusion

The results show that vitamin D status and VDBP levels are associated with liver cirrhosis severity and patients’ mortality, possibly through a proinflammatory immune response.

StephenW

肝硬化患者中与维生素D相关的免疫调节

克里斯托萨·特里亚托斯； Mariaa的Kalafateli；阿格莱托波洛，约阿纳，b；乔治亚州Diamantopoulou；斯潘底达（Spanidea），帕纳焦塔（Panagiota）I.b；玛丽娜（Michalaki），玛丽娜（Marinac）；格鲁吉亚Vourli；克里斯托萨·康斯坦塔基斯； Assimakopoulos，Stelios F.e; Spiliosf的Manolakopoulos； Gogos，Charalambose； Venetsanac的Kyriazopoulou； Athanasiab Mouzaki；康斯坦丁萨Thomopoulos作者信息

消化内科

血液学

帕特雷大学医院内分泌科，糖尿病和代谢疾病，帕特雷

d雅典大学医学院卫生学，流行病学和医学统计学系

帕特雷大学医院内科电子学系

雅典希腊希波克拉底总医院第二内科

2019年7月29日收到2019年9月24日接受

通讯地址：希腊帕特雷，里奥26504号里约热内卢州D. Stamatopoulou 4，D. Stamatopoulou，医学博士Christos Triantos，电话：+306972894651；传真：+302610625382;电子邮件：[email protected]
《欧洲胃肠病学和肝病学杂志》：2020年7月-第32卷-第7期-第867-876页
doi：10.1097 / MEG.0000000000001597

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抽象
目标

越来越多的证据表明，维生素D的状况与肝硬化的严重程度和患者的生存率有关。然而，与维生素D相关的免疫调节在肝代偿失调和与维生素D缺乏有关的患者死亡率方面的潜在作用仍然未知。本研究的目的是评估维生素D状况和维生素D结合蛋白（VDBP）水平与血清​​细胞因子和脂多糖结合蛋白（LBP）之间的关联，并检查它们在疾病严重程度和肝硬化病死亡率中的作用。
方法

该研究连续纳入了一百名高加索肝硬化患者。通过ELISA评估25（OH）D，VDBP和LBP浓度。细胞因子肿瘤坏死因子-a（TNF-a），白细胞介素6（IL-6），IL-1β，IL-8，IL-10和IL-12水平通过Cytometric Bead Array进行测定。
结果

25（OH）D水平与CP得分，MELD，IL-6和CP阶段呈负相关，而VDBP水平与CP得分，MELD，IL-6，IL-8，LBP和CP阶段呈负相关。具有25（OH）D缺乏和严重缺乏的肝硬化患者具有明显更高的CP评分，升高的IL-6水平和更低的VDBP水平。在多因素分析中，与患者生存相关的独立预后因素为CP B期[危险比= 6.75； 95％置信区间（CI）1.32，34.43; P = 0.022]，CP期C期（危险比= 7.39； 95％CI 1.41，38.81; P = 0.018），存在肝细胞癌（危险比= 4.50; 95％CI 1.54，13.13; P = 0.006）和25 （OH）D水平（危险比= 70.87; 95％CI 0.80，0.95; P = 0.002）。
结论

结果表明，维生素D的状态和VDBP水平与肝硬化严重程度和患者的死亡率有关，可能是通过促炎性免疫反应引起的。