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BMC Anesthesiology
Published in: BMC Anesthesiology 1/2018

Open Access 01-12-2018 | Research article

Increased circulating microRNA-122 is associated with mortality and acute liver injury in the acute respiratory distress syndrome

Authors: Tim Rahmel, Katharina Rump, Michael Adamzik, Jürgen Peters, Ulrich H. Frey

Published in: BMC Anesthesiology | Issue 1/2018

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Abstract

Background

Acute liver injury in patients with ARDS decreases survival but early stages may be easily missed due to the lack of sufficient biomarkers signalling its onset. Accordingly, we tested in ARDS patients the hypotheses that microRNA-122, the foremost liver-related microRNA (miR), 1) is an sensitive and specific early predictor for potential liver injury and 2) analysed its impact on 30-day-survival.

Methods

We collected clinical data and analysed blood samples from 119 ARDS patients within the first 24 h of ICU admission and from 20 patients undergoing elective abdominal non-liver surgery serving as controls. Total circulating miR was isolated from serum and relative miR-122 expression was measured (using specific probes and spiked-in miR-54), as were liver function and 30-day survival. Acute liver injury was defined as a total bilirubin concentration ≥ 3.0 mg/dl, an ALT activity ≥350 U/l, and an INR ≥2.0.

Results

30-day survival of the entire ARDS-cohort was 69% but differed between patients with normal liver function (77%) and acute liver injury (19% p <  0.001). miR-122 expression was 20fold higher in non-survivors (95%-CI 0.0149–0.0768; p = 0.001) and almost 4fold greater in survivors (95%-CI: 0.0037–0.0122; p = 0.005) compared to controls (95%-CI 0.0008–0.0034) and correlated with markers of liver cell integrity/function [ALT (p <  0.001, r = 0.495), AST (p <  0.001, r = 0.537), total bilirubin (p = 0.025, r = 0.206), INR (p = 0.001, r = 0.308), and GLDH (p <  0.001, r = 0.489)]. miR-122 serum expression discriminated survivors and non-survivors (AUC: 0.78) better than total bilirubin concentration (AUC: 0.66). Multivariable Cox-regression analysis revealed both acute liver injury (HR 7.6, 95%-CI 2.9–19.8, p <  0.001) and miR-122 (HR 4.4, 95%-CI 1.2–16.1, p = 0.02) as independent prognostic factors for 30-day mortality.

Conclusions

Increased miR-122 serum expression is an early and independent risk factor for 30-day mortality in ARDS patients and potentially reveal an acute liver injury earlier than the conventional markers of liver cell integrity.
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Metadata
Title
Increased circulating microRNA-122 is associated with mortality and acute liver injury in the acute respiratory distress syndrome
Authors
Tim Rahmel
Katharina Rump
Michael Adamzik
Jürgen Peters
Ulrich H. Frey
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2018
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-018-0541-5

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