Low serum concentration of apolipoprotein A-I is an indicator of poor prognosis in cirrhotic patients with severe sepsis

Tsai, Ming Hung; Peng, Yun; Chen, Yung Chang; Lien, Jau Min; Tian, Ya‐Chung; Ji, Fang; Weng, Hsu–Huei; Chen, Pang Chi; Yang, Chih Wei; Wu, Chia‐Chen

doi:10.1016/j.jhep.2008.12.024

Cited by 61 publications

(57 citation statements)

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“…In this regard, free radicals and oxidative stress have been implicated in the pathogenesis of acute pancreatitis and have been shown to correlate with the severity of pancreatitis [30,31]. Consistent with previous reports on critically ill patients [32-34], we showed that the levels of HDL and APO A-I at admission to ICU were significantly lower in non-survivors. We also demonstrated that the levels HDL and APO A-I were significantly lower in patients with persistent OF, while the levels of TNF-α, and IL-6 were lower in those with transient OF.…”

Section: Discussionsupporting

confidence: 92%

Serum levels of apolipoprotein A-I and high-density lipoprotein can predict organ failure in acute pancreatitis

et al. 2015

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IntroductionPredicting severity of pancreatitis is an important goal. Clinicians are still searching for novel and simple biomarkers that can better predict persistent organ failure (OF). Lipoproteins, especially high-density lipoprotein (HDL), and apolipoprotein A-I (APO A-I), have been shown to have anti-inflammation effects in various clinical settings. Severe acute pancreatitis (SAP) is associated with hypo-lipoproteinemia. We studied whether the concentrations of HDL and APO A-I can predict persistent OF in patients with predicted SAP admitted to the ICU.MethodsIn 66 patients with predicted SAP, we prospectively evaluated the relationship between lipid levels, inflammatory cytokines and clinical outcomes, including persistent OF and hospital mortality. Blood samples were obtained within 24 hours of admission to the ICU.ResultsHDL and APO A-I levels were inversely correlated with various disease severity scores. Patients with persistent OF had lower levels of HDL and APO A-I, while those with transient OF had lower levels of interleukin-6, tumor necrosis factor-α and lower rates of hospital mortality. Meanwhile, hospital non-survivors had lower concentrations of HDL, and APO A-I compared to the survivors. By using the area under the receiver operating characteristic (AUROC) curve, both HDL and APO A-I demonstrated an excellent discriminative power for predicting persistent OF among all patients (AUROC 0.912 and 0.898 respectively) and among those with OF (AUROC 0.904 and 0.895 respectively). Pair-wise comparison of AUROC showed that both HDL and APO A-I had better discriminative power than C-reactive protein to predict persistent OF.ConclusionsSerum levels of HDL and APO A-I at admission to the ICU are inversely correlated with disease severity in patients with predicted SAP and can predict persistent OF in this clinical setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0832-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Serum levels of apolipoprotein A-I and high-density lipoprotein can predict organ failure in acute pancreatitis

et al. 2015

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“…The metabolic disorder is one of the hallmarks of a patient with sepsis. Plasma lipoproteins, especially HDL, are markedly reduced during sepsis, and a number of clinical studies have pointed out that low plasma HDL is a prognostic factor in severe sepsis (4,5). It has been established that HDL plays a protective role in bacterial infection by scavenging circulatory levels of LPS (6,7).…”

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Toll-like Receptor (TLR) Signaling Interacts with CREBH to Modulate High-density Lipoprotein (HDL) in Response to Bacterial Endotoxin

Dandekar¹,

Qiu²,

Kim³

et al. 2016

Journal of Biological Chemistry

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Bacterial endotoxin can induce inflammatory and metabolic changes in the host. In this study, we revealed a molecular mechanism by which a stress-inducible, liver-enriched transcription factor, cAMP-responsive element-binding protein hepatic-specific (CREBH), modulates lipid profiles to protect the liver from injuries upon the bacterial endotoxin lipopolysaccharide (LPS). LPS challenge can activate CREBH in mouse liver tissues in a toll-like receptor (TLR)/MyD88-dependent manner. Upon LPS challenge, CREBH interacts with TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase that functions as a key mediator of TLR signaling, and this interaction relies on MyD88. Further analysis demonstrated that TRAF6 mediates K63-linked ubiquitination of CREBH to facilitate CREBH cleavage and activation. CREBH directly activates expression of the gene encoding Apolipoprotein A4 (ApoA4) under LPS challenge, leading to modulation of high-density lipoprotein (HDL) in animals. CREBH deficiency led to reduced production of circulating HDL and increased liver damage upon high-dose LPS challenge. Therefore, TLR/MyD88-dependent, TRAF6-facilitated CREBH activation represents a mammalian hepatic defense response to bacterial endotoxin by modulating HDL.

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“…En esta misma línea, un estudio en pacientes cirróticos con sepsis grave observó que los casos que fallecían poseían bajos niveles de colesterol HDL y apo A-I aún después de un ajuste según funcionalidad hepática 35 . Además, este estudio mostró la asociación entre la presencia de bajos niveles de colesterol HDL y apo A-I con altos niveles de IL-6 y FNT-α, los cuales se asocian a una enfermedad más grave y caracterizada por mayor compromiso multiorgá-nico 35 .…”

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“…Además, este estudio mostró la asociación entre la presencia de bajos niveles de colesterol HDL y apo A-I con altos niveles de IL-6 y FNT-α, los cuales se asocian a una enfermedad más grave y caracterizada por mayor compromiso multiorgá-nico 35 . Importantemente, se estableció que bajos niveles de apo A-I constituyen un marcador independiente de mortalidad a 90 días con un riesgo relativo que supera los scores clínicos SOFA (sequential organ failure assessment) y MELD (model for end-stage liver disease) que indican la gravedad de la enfermedad hepática crónica.…”

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“…Importantemente, se estableció que bajos niveles de apo A-I constituyen un marcador independiente de mortalidad a 90 días con un riesgo relativo que supera los scores clínicos SOFA (sequential organ failure assessment) y MELD (model for end-stage liver disease) que indican la gravedad de la enfermedad hepática crónica. De esta forma, los niveles de colesterol HDL y de apo A-I se correlacionan con la reserva hepática y podrían ser usados como nuevos indicadores pronósticos en pacientes cirróticos ante eventuales complicaciones sépticas 35 . Adicionalmente, un estudio observacional retrospectivo en una unidad de pacientes críticos pediátricos reportó que los pacientes con meningococcemia o shock séptico por N. meningitidis presentaron niveles de colesterol total, colesterol LDL y colesterol HDL disminuidos al ingreso, destacando una mayor hipocolesterolemia en pacientes con shock séptico que finalmente fallecieron.…”

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Papel protector de las lipoproteínas de alta densidad en sepsis: aspectos básicos e implicancias clínicas

Contreras-Duarte

Varas

Awad

et al. 2014

Rev. chil. infectol.

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Low serum concentration of apolipoprotein A-I is an indicator of poor prognosis in cirrhotic patients with severe sepsis

Cited by 61 publications

References 53 publications

Serum levels of apolipoprotein A-I and high-density lipoprotein can predict organ failure in acute pancreatitis

Serum levels of apolipoprotein A-I and high-density lipoprotein can predict organ failure in acute pancreatitis

Toll-like Receptor (TLR) Signaling Interacts with CREBH to Modulate High-density Lipoprotein (HDL) in Response to Bacterial Endotoxin

Papel protector de las lipoproteínas de alta densidad en sepsis: aspectos básicos e implicancias clínicas

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