Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test). A prospective study.

Magnus F Kaffarnik,Tilo Wuensch,Maciej Malinowski,Navid Ahmadi,Johann Pratschke,Johan F Lock,Martin Stockmann,Chiara Lazzeri

doi:10.1371/journal.pone.0178237

Magnus F Kaffarnik, Tilo Wuensch + Show 6 more

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https://doi.org/10.1371/journal.pone.0178237

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Abstract

AimTo investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test) and endothelin-1, TNF-α and IL-6 in septic surgical patients.Methods28 septic patients (8 female, 20 male, age range 35–80y) were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction) for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test.ResultsGroup B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10). For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005). IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001), TNF-α (-0.515; P <0.001) and IL-6 (-0.590; P <0.001).ConclusionsSepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

Highlights

The liver is a key organ in the pathophysiological response to bacterial endotoxin in sepsis
Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin1, TNF-α and IL-6
Septic shock is accompanied by increased plasma endothelin-1 (ET-1) levels

Summary

Introduction

The liver is a key organ in the pathophysiological response to bacterial endotoxin in sepsis. Patients with septic shock develop liver failure in up to 50% of the cases and liver failure indicates poor outcome in critically ill patients [1,2]. Septic shock is accompanied by increased plasma endothelin-1 (ET-1) levels. The regulation of liver perfusion during sepsis largely depends on ET-1-receptor activity. Experimental data indicate that bacterial endotoxin exposure leads to elevation of liver ET-1 due to release of tumor necrosis factor (TNF-α) and other inflammatory cytokines by Kupffer cells. These mediators bind to receptors on liver endothelial cells and cause increased liberation of ET-1. Elevated ET-1 provokes a strong sinusoidal vasoconstriction, which may lead to a microcirculatory impairment of liver parenchyma with heterogeneous perfusion, focal hypoxia and, to hepatic failure [5,6,7,8]

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