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Neutrophil gelatinase-associated lipocalin useful biomarker in ACLF

Urine neutrophil gelatinase-associated lipocalin was prevalent in patients with acute-on-chronic liver failure and correlated with prognosis, suggesting it was a successful biomarker for identifying this type of liver disease in patients with cirrhosis.

“The results of the study show that urine [neutrophil gelatinase-associated lipocalin] levels in patients with [acute-on-chronic liver failure] were significantly increased compared to those of patients without [acute-on-chronic liver failure], and among patients without [acute-on-chronic liver failure], higher levels of urine [neutrophil gelatinase-associated lipocalin] were associated with development of [acute-on-chronic liver failure],” Pere Ginès, MD, of the Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain, told Healio.com/Hepatology.

Pere Ginès

The researchers analyzed urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) of 716 patients hospitalized for complications of cirrhosis enrolled in the CANONIC study. Of these, 146 had acute-on-chronic liver failure (ACLF). LCN2 gene expression — a gene that encodes NGAL protein — was also measured in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF, to determine if it was overexpressed in the liver among the patients with ACLF.

Analyses showed patients with ACLF had increased urine NGAL (108 μg/g creatinine) compared with patients without ACLF patients (29 μg/g creatinine; P < .001). Increased urine NGAL was an independent predictor for ACLF. This association remained even after adjusting for kidney function or exclusion of variables present in ACLF definition.

In addition, urine NGAL was an independent predictor for 28-day transplant-free mortality together with MELD score and leukocyte count, with an area under the operating curve of 0.88 (0.83–0.92).

The LCN2 gene was upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin (r = 0.79) and internal normalized ratio (r = 0.67), MELD (r = 0.68) and interleukin-6 (r = 0.65; P < .001 for all).

“The hepatic gene expression of LCN2 was markedly increased in patients with ACLF compared to patients with decompensated cirrhosis without ACLF and patients with compensated cirrhosis, suggesting a contribution of hepatic expression to NGAL levels,” Ginès told Healio.com/Hepatology. 

Researchers also observed that urine NGAL improved the accuracy of MELD in the prediction of prognosis of ACLF.

“The results of the study show a significant increase of urine NGAL levels and LCN2 hepatic gene expression in patients with ACLF, indicating that urine NGAL levels are an excellent biomarker of prognosis in patients hospitalized for acute decompensation of cirrhosis and improve the prognostic accuracy of existing prognostic markers, especially MELD score,” Ginès said. “Measurement of urine NGAL may be helpful in clinical practice for decision-making in patients with cirrhosis.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.