Circulating bile acids predict outcome in critically ill patients

Horvatits, Thomas; Drolz, Andreas; Rutter, Karoline; Roedl, Kevin; Langouche, Lies; Berghe, Greet Van den; Fauler, Günter; Meyer, Brigitte; Hülsmann, Martin; Gisslinger, Heinz; Trauner, Michael; Fuhrmann, Valentin

doi:10.1186/s13613-017-0272-7

Cited by 53 publications

(49 citation statements)

References 61 publications

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“…(12,16,18) Total BAs potentially represent a feasible biomarker for severity of disease, as they predict short-time mortality independently of serum bilirubin and severity of underlying disease as reported in a recent study. (18) MicroRNAs, central regulators of posttranscription gene expression, may serve as potential biomarkers for several liver diseases. (28) However, their relevance in ICU-related liver injury remains to be determined.…”

Section: Diagnosismentioning

confidence: 85%

“…Up to 20% of patients develop cholestasis during their intensive care unit (ICU) stay . However, cholestatic alterations are more frequently found in septic shock (33%) than in cardiogenic shock (21%) or following surgery (5%), as indicated in Supporting Table …”

Section: Jaundice and Cholestatic Dysfunctionmentioning

confidence: 99%

“…BAs also have important metabolic signaling functions that regulate energy, lipid, and glucose homeostasis . BAs have both pro‐inflammatory and anti‐inflammatory properties, probably depending on serum concentrations and state of critical illness . It is under debate whether cholestasis and BA retention reflect a distinct pathophysiological condition, an expression of severity of organ failure or instead a compensatory mechanism with potential beneficial actions (e.g., through inhibitions of hepatic inducible nitric oxide synthase [iNOS] activity) (Fig.…”

Section: Jaundice and Cholestatic Dysfunctionmentioning

confidence: 99%

“…(16) Recent insights demonstrate that alterations of hepatic transport and metabolism already occur in the first hours of critical illness. (18)(19)(20) Apart from infections with gram-negative bacteria, malperfusion, retention of toxic molecules, and pathogen-associated molecular patterns contribute to cholestasis in critical illness through inflammation-mediated repression of hepatobiliary transporters and reduced canalicular contractility, resulting in impaired bile flow and BA retention. (21,22) BAs also have important metabolic signaling functions that regulate energy, lipid, and glucose homeostasis.…”

Section: Pathophysiology Of Cholestasis In the Critically Illmentioning

confidence: 99%

“…(3) Increased serum BA was significantly associated with elevated 28-day mortality in critically ill patients independently of bilirubin levels and severity of underlying disease. (18,19)…”

Section: Clinical Presentation and Course Of Diseasementioning

confidence: 99%

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Liver Injury and Failure in Critical Illness

et al. 2019

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The frequency of acquired liver injury and failure in critical illness has been significantly increasing over recent decades. Currently, liver injury and failure are observed in up to 20% of patients in intensive care units and are associated with significantly increased morbidity and mortality. Secondary forms of liver injury in critical illness are divided primarily into cholestatic, hypoxic, or mixed forms. Therefore, sufficient knowledge of underlying alterations (e.g., hemodynamic, inflammatory, or drug induced) is key to a better understanding of clinical manifestations, prognostic implications, as well as diagnostic and therapeutic options of acquired liver injury and failure. This review provides a structured approach for the evaluation and treatment of acquired liver injury and failure in critically ill patients.

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Section: Diagnosismentioning

confidence: 85%

Section: Jaundice and Cholestatic Dysfunctionmentioning

confidence: 99%

Section: Jaundice and Cholestatic Dysfunctionmentioning

confidence: 99%

Section: Pathophysiology Of Cholestasis In the Critically Illmentioning

confidence: 99%

“…(3) Increased serum BA was significantly associated with elevated 28-day mortality in critically ill patients independently of bilirubin levels and severity of underlying disease. (18,19)…”

Section: Clinical Presentation and Course Of Diseasementioning

confidence: 99%

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Liver Injury and Failure in Critical Illness

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Neutrophil Gelatinase‐Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study

et al. 2019

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Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis. (Hepatology 2019;70:319-333).A cute kidney injury (AKI) is a common complication of patients with advanced cirrhosis hospitalized for an acute decompensation. (1)(2)(3)(4)(5)(6) Importantly, the occurrence of AKI impairs prognosis. The 3-month probability of mortality after AKI is very high, ranging from 28% to 47%. (3)(4)(5)(6)(7)(8) Mortality

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Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

et al. 2019

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Critical illness is associated with a disturbed regulation of gastrointestinal hormones resulting in functional and metabolic anomalies. Fibroblast growth factor 19 (FGF19) is an ileum‐derived metabolic hormone induced by bile salts upon gallbladder emptying after enteral nutrient stimulation. Our aim was to study the nutrient‐stimulated FGF19 response in 24 patients admitted to the intensive care unit (ICU) compared with 12 healthy controls. All subjects received intraduodenal high‐lipid nutrient infusion for 120 minutes. Blood was collected every 30 minutes until 1 hour after infusion, and gallbladder emptying was studied by ultrasound. Serum levels of bile salts and FGF19 were assessed. ICU patients had significantly higher fasting bile salt serum levels compared with controls, whereas FGF19 serum levels were similar. In both groups, nutrient infusion elicited substantial bile salt elevations (P < 0.001), peaking at 90 minutes, albeit with a significantly lower peak in the ICU patients (P = 0.029). In controls, FGF19 was significantly elevated relative to baseline from 120 minutes onward (P < 0.001). In ICU patients, the FGF19 response was blunted, as reflected by significantly lower FGF19 elevations at 120, 150, and 180 minutes (P < 0.05) and significantly lower area under the curve (AUC) values compared with controls (P < 0.001). Gallbladder dysmotility was associated with the impaired FGF19 response in critical illness. The gallbladder ejection fraction correlated positively with FGF19 AUC values (ρ = +0.34, P = 0.045). In 10 of 24 ICU patients, gallbladder emptying was disturbed. These patients had significantly lower FGF19 AUC values (P < 0.001). Gallbladder emptying and the FGF19 response were respectively disturbed or absent in patients receiving norepinephrine. Conclusion: The nutrient‐stimulated FGF19 response is impaired in ICU patients, which is mechanistically linked to gallbladder dysmotility in critical illness. This may contribute to disturbed liver metabolism in these patients and has potential as a nutritional biomarker.

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Circulating bile acids predict outcome in critically ill patients

Cited by 53 publications

References 61 publications

Liver Injury and Failure in Critical Illness

Liver Injury and Failure in Critical Illness

Neutrophil Gelatinase‐Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study

Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

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