Abstract
BackgroundAcute 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.MethodsWe 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.Results30-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.ConclusionsIncreased 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.
Highlights
Acute liver injury in patients with Acute respiratory distress syndrome (ARDS) decreases survival but early stages may be missed due to the lack of sufficient biomarkers signalling its onset
Concerning markers of liver cell integrity, Aspartate aminotransferase activity (AST), Alanine aminotransferase activity (ALT), bilirubin, and GLDH were all significantly increased in ARDS non-survivors upon admission (Table 1) with bilirubin concentration showing a peak of 7.2 mg/dl in non-survivors on day 12
This study, to our knowledge, is the first to assess whether miR-122 serum levels are associated with altered survival and indicates of an acute liver injury in patients suffering from ARDS
Summary
Acute liver injury in patients with ARDS decreases survival but early stages may be missed due to the lack of sufficient biomarkers signalling its onset. Diagnostic options refer to the early detection of an acute liver injury, in patients suffering from ARDS, and comprise of standard biochemical liver tests such as transaminase activity, bilirubin concentration, or markers for liver related synthesis like the liver dependent coagulation factors [6]. In this context, bilirubin concentration is a predictor for ARDS outcome, and indicates acute liver dysfunction in ARDS patients [5]. All these tests have a low specificity to determine the presence of acute liver injury in its early phase [7,8,9] implying a need for reliable biomarkers for an early prediction
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