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Observational Study
. 2019 Jan;39(1):106-114.
doi: 10.1111/liv.13916. Epub 2018 Jul 30.

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients

Delphine Weil  1   2 , Jean-Paul Pais de Barros  3   4 , Guillaume Mourey  5 , Caroline Laheurte  5 , Benoit Cypriani  6 , Nicolas Badet  7 , Eric Delabrousse  7 , Emilie Grandclément  6 , Vincent Di Martino  1   2 , Philippe Saas  5 , Laurent Lagrost  3   4 , Thierry Thévenot  1   2
Affiliations
Observational Study

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients

Delphine Weil et al. Liver Int. 2019 Jan.

Abstract

Background & aims: The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage.

Methods: Plasma from 90 noninfected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by high-performance liquid chromatography coupled with mass spectrometry.

Results: 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103 ng/mL, P = 0.005). Patients with severe acute alcoholic hepatitis (n = 16; 113 vs 74 ng/mL, P = 0.012), diabetic patients (n = 22; 99 vs 70 ng/mL, P = 0.028) and those not receiving beta blockers (n = 44; 98 vs 72 ng/mL, P = 0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n = 7; 144 vs 76 ng/mL, P = 0.45) or SIRS (n = 10; 106 vs 75 ng/mL, P = 0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR = 4.39; 95%CI = 1.79-10.76) or MELD (OR = 8.24; 95%CI = 3.19-21.32) scores. Patients dying from liver insufficiency (n = 6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75 ng/mL, P = 0.089).

Conclusions: In noninfected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3-HM appears reliable to detect transient endotoxaemia and promising to manage the follow-up of cirrhotic patients.

Keywords: 3-hydroxymyristate; bacterial translocation; cirrhosis; endotoxaemia; lipopolysaccharide; portal hypertension.

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