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A comparison of Gc globulin and neutrophil gelatinase-associated lipocalin in patients with liver disease

Introduction

Gc globulin, a hepatically synthesized actin binding protein, is known to decrease in both acute and chronic liver disease, and low levels are associated with poor prognosis. Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family of proteins, has been shown to be an early biomarker of ischaemic renal damage. We prospectively investigated the use of these proteins as markers of severity of illness and prognostication in acute and acute-on-chronic liver failure requiring intensive care.

Methods

NGAL and Gc globulin were measured on admission to our unit using a sandwich ELISA technique (AntibodyShop®) in 17 patients with acute liver failure (ALF) and 11 patients with acute-on-chronic liver disease (ACLD). Biochemical and physiological variables were collected prospectively and entered into a physiological database (ICARE). All measurements were taken on day 1 of admission. Results are expressed as the median and interquartile range.

Results

Admission parameters: serum creatinine 185 μmol/l (89–266), urine output/24 hours: 340 ml (0–1,111), APACHE II score 20 (15–25), lactate 2.6 (1.8–4.68), INR 2.6 (1.6–3.8) and AST 1,404 (124–6,349). There were significant differences between median Gc globulin in ALF patients compared with ACLD: 25 mg/l (10–50) vs 50 mg/l (25–129), P = 0.036. No significant differences were seen for NGAL. Gc globulin correlated with admission creatinine (r = 0.44, P < 0.01), INR (r = 0.68, P < 0.01), and SOFA score (r = 0.419, P < 0.01) in both patient groups. These relationships persisted when admission Gc globulin was examined in regard to day 5 parameters. Admission Gc globulin correlated with D3 urine output (r = 0.619, P < 0.001). NGAL correlated with urine output throughout the first 5 days of admission (r = -0.593 on day 1, r = -0.674 on day 3, P < 0.001) and also with SOFA score. High admission NGAL was associated with requirement for renal replacement therapy on day 3 (ROC AUC 0.91 (0.895–1.022, P < 0.001)), outperforming both admission Gc globulin and admission creatinine. A low admission Gc globulin more accurately predicted the need for haemofiltration on day 5 (AUC 0.889, 0.734–1.044, P < 0.007) than either NGAL or creatinine on admission.

There were significant differences observed for Gc globulin examining 30-day survival (transplantation from ITU being analysed as 'death'): 50 mg/l (29–94) vs 18 (4–40), respectively, AUC 0.813, P = 0.006. There were no significant differences in NGAL values between survivors and nonsurvivors for the whole group. NGAL was significantly lower in survivors than nonsurvivors in the ACLD group (AUC 0.875, P = 0.47).

Conclusion

Gc globulin and NGAL are potentially useful methods of identifying patients with a particularly poor prognosis and those needing renal replacement therapy. Further larger prospective studies are needed to elucidate their exact role not only in liver disease but also in the general ITU population.

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Portal, A., Austin, M., Bruce, M. et al. A comparison of Gc globulin and neutrophil gelatinase-associated lipocalin in patients with liver disease. Crit Care 11, P394 (2007). https://0-doi-org.brum.beds.ac.uk/10.1186/cc5554

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Keywords

  • Liver Disease
  • Renal Replacement Therapy
  • Urine Output
  • Acute Liver Failure
  • Actin Binding Protein