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