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. 2016 Mar 3;11(3):e0150440.
doi: 10.1371/journal.pone.0150440. eCollection 2016.

Plasma Glutamine Concentrations in Liver Failure

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Free PMC article

Plasma Glutamine Concentrations in Liver Failure

Gunnel Helling et al. PLoS One. .
Free PMC article

Abstract

Background: Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations.

Methods: Four different groups of patients were studies; chronic liver failure (n = 40), acute on chronic liver failure (n = 20), acute fulminant liver failure (n = 20), and post-hepatectomy liver failure (n = 20). Child-Pugh and Model for End-stage Liver Disease (MELD) scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion.

Results: All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100), severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong.

Conclusion: Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Plasma glutamine concentration in relation to the Child-Pugh score as a reflection of the degree of liver failure.
In panel A chronic liver failure (n = 40), in panel B acute-on-chronic liver insufficiency (n = 20), in panel C acute fulminant liver failure (n = 20), and in panel D on the second postoperative day following major liver resection (n = 20). Open round symbols denote alive and filled round symbols denote dead 48 months after sampling. A thick sign on symbols in panel D denotes mortality in the acute phase. Squared inclusion denotes liver transplanted. The hatched area corresponds to the reference interval for plasma glutamine concentration. The rs-values for Spearman’s rank correlations together with the P-values for statistical significance are included in all four panels. Observe the different scales of the y-axes.
Fig 2
Fig 2. Plasma glutamine concentration in relation to the MELD score as a reflection of the degree of liver failure.
In panel A chronic liver failure (n = 40), in panel B acute-on-chronic liver failure (n = 20), in panel C acute fulminant liver failure (n = 20), and in panel D on the second postoperative day following major liver resection (n = 20). Open round symbols denote alive and filled round symbols denote dead 48 months after sampling. Squared inclusion denotes liver transplanted. A thick sign on symbols in panel D denotes mortality in the acute phase. The hatched area corresponds to the reference interval for plasma glutamine concentration. The rs-values for Spearman’s rank correlations together with the P-values for statistical significance are included in all four panels. Observe the different scales of the y-axes.
Fig 3
Fig 3
Longitudinal plasma glutamine concentration during hospital stay (or until acute liver transplantation in panel C) in panel B acute-on-chronic liver failure (n = 20), in panel C acute fulminant liver failure (n = 20), and in panel D following major liver resection (n = 20). Bold lines denote ongoing IV glutamine supplementation whilst staying in the ICU. Group A, chronic liver failure, was not followed longitudinally. Observe the different scales of the y-axes. In Group B, acute on chronic liver failure (n = 20), the decompensation etiologies or reasons for ICU admission were: gastrointestinal bleeding (n = 8), severe sepsis/septic shock (n = 5), spontaneous bacterial peritonitis (n = 3), hepatorenal syndrome (n = 2), and encephalopathy West-Haven grade 4 (n = 2). Plasma glutamine concentration at ICU admission was 968 (115–4,184) μmol/L. Three patients were below and 11 patients were above the reference interval of 400–930 μmol/L. In Group C, acute fulminant liver failure (n = 20), the etiologies of liver failure were paracetamol intoxication (n = 9), ischemia (n = 4), acute viral hepatitis (n = 2), mushroom poisoning (n = 1), Wilson’s disease (n = 1), and unknown (n = 3). Plasma glutamine concentration at hospital admission was 1,116 (411–5,744) μmol/L. No patient was below and 11 patients were above the reference interval of 400–930 μmol/L. In Group D, patients undergoing liver resection (n = 20), the indications for liver resection were: metastatic colorectal cancer (n = 14), cholangiocarcinoma (n = 5) and hepatocellular cancer (n = 1). Liver resection was 50–80%, and median peroperative bleeding was 1,800 (400–20,500) mL. Four patients were admitted to the ICU during the postoperative course. Plasma glutamine concentration at transfer from recovery room to high dependency unit on day 1–2 after surgery was 717 (365–2,468) μmol/L. One patient was below and four patients were above the reference interval of 400–930 μmol/L.
Fig 4
Fig 4. Plasma glutamine concentration dichotomized above or below 930 μmol/L, the upper limit of the reference range, for the total group of patients with liver failure (n = 100).
The high out-of-normal–range values were then related to symptoms of liver failure as reflected by the Child-Pugh and MELD scores by receiver operator characteristics curves (ROC curves).

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Grant support

The study was supported by grants from the Swedish Medical Research Council (projects 04210 and 14244) and the County Council of Stockholm (projects 502033 and 511126). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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