Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis

被引：125

作者：

Ariza, X. ^{[1
,2
,3
,4
]}

Graupera, I. ^{[1
,2
,3
,4
]}

Coll, M. ^{[3
,4
]}

Sola, E. ^{[1
,2
,3
,4
]}

Barreto, R. ^{[1
,2
,3
,4
]}

Garcia, E. ^{[5
]}

Moreira, R. ^{[1
,2
,3
,4
]}

Elia, C. ^{[1
,2
,3
,4
]}

Morales-Ruiz, M. ^{[2
,3
,4
,6
]}

Llopis, M. ^{[3
,4
]}

Huelin, P. ^{[1
,2
,3
,4
]}

Sole, C. ^{[1
,2
,3
,4
]}

Fabrellas, N. ^{[2
,3
]}

Weiss, E. ^{[7
,8
,9
,10
,11
]}

Nevens, F. ^{[12
]}

Gerbes, A. ^{[13
]}

Trebicka, J. ^{[14
]}

Saliba, F. ^{[15
]}

Fondevila, C. ^{[2
,3
,4
,16
]}

Hernandez-Gea, V. ^{[1
,2
,3
,4
,17
]}

Fernandez, J. ^{[1
,2
,3
,4
]}

Bernardi, M. ^{[18
]}

Arroyo, V. ^{[19
]}

Jimenez, W. ^{[2
,3
,4
,6
]}

Deulofeu, C. ^{[5
]}

Pavesi, M. ^{[4
]}

Angeli, P. ^{[20
]}

Jalan, R. ^{[21
]}

Moreau, R. ^{[7
,8
,9
,10
,11
]}

Sancho-Bru, P. ^{[3
,4
]}

Gines, P. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Barcelona, Hosp Clin Barcelona, Liver Unit, Barcelona, Spain

[2] Univ Barcelona, Barcelona, Spain

[3] Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain

[4] CIBEReHD, Barcelona, Spain

[5] EASL CLIF Consortium, Data Management Ctr, Barcelona, Spain

[6] Hosp Clin Barcelona, Dept Biochem & Mol Genet, Barcelona, Spain

[7] Hop Beaujon, INSERM, U1149, CRI, Clichy, France

[8] INSERM, U1149, CRI, Paris, France

[9] Univ Paris Diderot, UMRS1149, Paris, France

[10] Hop Beaujon, AP HP, Dept Hosp Univ DHU UNITY, Serv Hepatol, Clichy, France

[11] ComUE Sorbonne Paris Cite, Lab Excellence Inflamex, Paris, France

[12] Univ Leuven, KU Leuven, Univ Hosp Leuven, Div Liver & Biliopancreat Disorders, Leuven, Belgium

[13] Univ Hosp LMU Munich, Dept Internal Med 2, Liver Ctr Munich, Munich, Germany

[14] Univ Bonn, Dept Internal Med 1, Bonn, Germany

[15] Hop Paul Brousse, Villejuif, France

[16] Hosp Clin Barcelona, Hepatobiliary Surg & Liver Transplant, Barcelona, Spain

[17] Hosp Clin Barcelona, Liver Unit, Hepat Hemodynam Lab, Barcelona, Spain

[18] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy

[19] EASL CLIF Consortium, Barcelona, Spain

[20] Univ Padua, Dept Surg, Unit Hepat Emergencies & Liver Transplantat, Padua, Italy

[21] UCL, Sch Med, Inst Liver & Digest Hlth, Liver Failure Grp,Royal Free Hosp, Mortimer St, London W1N 8AA, England

来源：

JOURNAL OF HEPATOLOGY | 2016年 / 65卷 / 01期

关键词：

Lipocalin-2; NGAL; Acute-on-chronic liver failure; Biomarker; TUMOR-NECROSIS-FACTOR; EMERGENCY-DEPARTMENT; BACTERIAL-INFECTIONS; INJURY; EXPRESSION; DISEASE; SERUM; NGAL; MICE; SENSITIVITY;

D O I：

10.1016/j.jhep.2016.03.002

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Background & Aims: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. Methods: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. Results: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73) mu g/g creatinine; p < 0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28 day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r = 0.79; p < 0.001 and r = 0.67; p < 0.001), MELD (r = 0.68; p < 0.001) and Interleukin-6 (r = 0.65; p < 0.001). Conclusions: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. Lay summary: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：57 / 65

页数：9

共 35 条

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