Role of angiogenic factors/cell adhesion markers in serum of cirrhotic patients with hepatopulmonary syndrome

Raevens, Sarah; Coulon, S.; Steenkiste, Christophe Van; Colman, Roos; Verhelst, Xavier; Vlierberghe, Hans Van; Geerts, Anja; Perkmann, Thomas; Horvatits, Thomas; Fuhrmann, Valentin; Colle, Isabelle

doi:10.1111/liv.12579

Cited by 26 publications

(23 citation statements)

References 27 publications

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“…Altered gut integrity due to increased intestinal permeability and bacterial translocation represent important triggers of sepsis and sepsis-related organ dysfunction [45]. Serum BA levels are able to directly trigger inflammatory processes via cytokine expression [25–27]. Conversely, BA also have anti-inflammatory and immunosuppressive properties mediated by FXR and TGR5 via modulating anti-inflammatory gene expression [17, 46, 47] Thus, BAs may have both pro- and anti-inflammatory actions depending on the time course and concentrations of serum BA levels during sepsis [48].…”

Section: Discussionmentioning

confidence: 99%

Circulating bile acids predict outcome in critically ill patients

Horvatits

Drolz

Rutter

et al. 2017

Ann. Intensive Care

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BackgroundJaundice and cholestatic hepatic dysfunction are frequent findings in critically ill patients associated with increased mortality. Cholestasis in critically ill patients is closely associated with stimulation of pro-inflammatory cytokines resulting in impaired bile secretion and subsequent accumulation of bile acids.Aim of this study was to evaluate the clinical role of circulating bile acids in critically ill patients.MethodsTotal and individual serum bile acids were assessed via high-performance liquid chromatography in 320 critically ill patients and 19 controls.ResultsTotal serum bile acids were threefold higher in septic than cardiogenic shock patients and sixfold higher than in post-surgical patients or controls (p < 0.001). Elevated bile acid levels correlated with severity of illness, renal dysfunction and inflammation (p < 0.05). Total bile acids predicted 28-day mortality independently of sex, age, serum bilirubin and severity of illness (HR 1.041, 95% CI 1.013–1.071, p < 0.005). Best prediction of mortality of total bile acids was seen in patients suffering from septic shock.ConclusionsIndividual and total BAs are elevated by various degrees in different shock conditions. BAs represent an early predictor of short-term survival in a mixed cohort of ICU patients and may serve as marker for early risk stratification in critically ill patients. Future studies should elucidate whether modulation of BA metabolism and signalling influences the clinical course and outcome in critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0272-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Circulating bile acids predict outcome in critically ill patients

Horvatits

Drolz

Rutter

et al. 2017

Ann. Intensive Care

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“…Several lines of evidence in experimental and human HPS support that vascular remodeling, endothelial dysfunction, and angiogenesis (new blood vessel formation from preexisting vessels) contribute to HPS development. In humans, single‐nucleotide polymorphisms in genes involved in the regulation of angiogenesis, including endoglin (ENG) and von Willebrand factor (vWF), are associated with the risk of HPS; and circulating levels of these factors, as well as vascular cell adhesion molecule 1, are increased in serum of patients with cirrhosis and HPS compared to those without HPS . In CBDL animals, scanning electron microscopic evaluation of pulmonary vascular casts showed, in addition to crypts representing sites of intravascular macrophage adhesion, increased microvascular density and capillary diameter, along with signs of intussusceptive angiogenesis and the presence of direct vascular communications .…”

Section: Pathogenesis Of Hps: Lessons From Experimental Modelsmentioning

confidence: 99%

Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models

Raevens

Fallon

2018

Hepatology

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Hepatopulmonary syndrome (HPS) is a relatively common and potentially severe pulmonary complication of cirrhosis with increased risk of mortality. In experimental models, a complex interaction between pulmonary endothelial cells, monocytes, and the respiratory epithelium, which produces chemokines, cytokines, and angiogenic growth factors, causes alterations in the alveolar microvasculature, resulting in impaired oxygenation. Model systems are critical for evaluating mechanisms and for preclinical testing in HPS, due to the challenges of evaluating the lung in the setting of advanced liver disease in humans. This review provides an overview of current knowledge and recent findings in the rodent common bile duct ligation model of HPS, which recapitulates many features of human disease. We focus on the concepts of endothelial derangement, monocyte infiltration, angiogenesis, and alveolar type II cell dysfunction as main contributors and potential targets for therapy.

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“…Finally, whether monocytes adhere in the lung vasculature in human HPS, via increased circulating levels of adhesion molecules, and whether inhibition of TNFα or bacterial translocation across the gastrointestinal tract alter the severity of HPS are not well defined [28,33,39,40].…”

Section: Pathogenesismentioning

confidence: 99%