Low‐grade endotoxemia and platelet activation in cirrhosis

Raparelli, Valeria; Basili, Stefania; Carnevale, Roberto; Napoleone, Laura; Ben, Maria Del; Nocella, Cristina; Bartimoccia, Simona; Lucidi, C.; Talerico, Giovanni; Riggio, Oliviero; Violi, Francesco

doi:10.1002/hep.28853

Cited by 115 publications

(119 citation statements)

References 33 publications

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“…In the context of AF, we previously demonstrated that adherence to Med‐diet had several beneficial effects, including a reduction of systemic oxidative stress26 and platelet activation,35 which were in turn associated with a lower rate of MACE. The novel finding of the present study is in the inverse association between adherence to Med‐diet and circulating LPS, which provides a novel insight into the putative anti‐inflammatory effect exerted by Med‐diet 31. It is interesting to note that, among the Med‐diet nutrients, fruits and legumes were those showing a striking association with lower LPS, indicating a relevant role for low‐fat‐content food in modulating circulating LPS 36…”

Section: Discussionsupporting

confidence: 50%

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

Pastori

Carnevale

Nocella

et al. 2017

JAHA

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136

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BackgroundGut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut‐derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med‐diet).Methods and ResultsThis was a prospective single‐center study including 912 AF patients treated with vitamin K antagonists (3716 patient‐years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med‐diet (n=704), and urinary excretion of 11‐dehydro‐thromboxane B2 (TxB2, n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS, respectively (log‐rank test P=0.004). Log‐LPS (hazard ratio 1.194, P=0.009), age (hazard ratio 1.083, P<0.001), and previous cerebrovascular (hazard ratio 1.634, P=0.004) and cardiac events (hazard ratio 1.822, P<0.001) were predictors of MACE. In the whole cohort, AF (versus sinus rhythm) (β 0.087, P=0.014) and low‐density lipoprotein cholesterol (β 0.069, P=0.049) were associated with circulating LPS. Furthermore, Med‐diet score (β −0.137, P<0.001) was predictive of log‐LPS, with fruits (β −0.083, P=0.030) and legumes (β −0.120, P=0.002) negatively associated with log‐LPS levels. Log‐LPS and log‐TxB2 were highly correlated (r=0.598, P<0.001). Log‐LPS (β 0.574, P<0.001) and Med‐diet score (β −0.218, P<0.001) were significantly associated with baseline urinary excretion of TxB2.ConclusionsIn this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med‐diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

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Section: Discussionsupporting

confidence: 50%

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

Pastori

Carnevale

Nocella

et al. 2017

JAHA

Self Cite

136

View full text Add to dashboard Cite

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“…However, a recent systematic review and meta‐analysis of anticoagulation in cirrhotic patients with portal vein thrombosis, therapeutic anticoagulation was not associated with major or minor bleeding with some studies even reporting lower rates of spontaneous variceal bleeding . Evidence also suggests that a hypercoagulable state persists in cirrhotic patients with thrombocytopenia, at least in part, due to a process in which lipopolysaccharide‐induced platelet sensitisation results in enhanced in vivo platelet activation . The functional effect of thrombocytopenia in cirrhosis is also influenced by intercurrent illnesses, including sepsis and acute renal impairment, both of which can impact platelet function and are commonly seen in hospitalised patients with decompensated cirrhosis .…”

Section: Discussionmentioning

confidence: 99%

Suboptimal use of pharmacological venous thromboembolism prophylaxis in cirrhotic patients

Yang

Alukaidey

Croucher

et al. 2018

Internal Medicine Journal

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“…Twenty‐four studies reported on 29 statistically significant biomarkers and association with altered IP . Two studies reported that fasting glucose had a weak positive correlation with IP (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…Two studies used both zonulin and the dual sugar test and reported a high positive correlation between the two tests ( ρ = 0.891; P = 0.05) (Table ). However, mixed evidence was reported for the strength of association between zonulin and LPS with a weak to moderate positive correlation reported ( ρ = 0.545; P < 0.001); although, one study reported LPS to independently correlate with zonulin levels ( β = 0.002; 95% CI: 0.001, 0.003; P = 0.002) (Table ). The dual sugar test was also reported to have a moderate to high positive correlation with gastroduodenal permeability according to one study ( r = 0.68; P < 0.0001, r = 0.88; P < 0.0001) …”

Section: Resultsmentioning

confidence: 99%

“…Comorbidity of chronic diseases such as diabetes, liver disease, metabolic syndrome, kidney disease and obesity were identified to increase the risk of IP . Moreover, the severity and activity of chronic health conditions including liver disease, metabolic syndrome, PCOS, coeliac disease and BMI were reported to correlate with the degree of IP. The notion that IP correlates with disease severity is further supported as the severity of particular risk factors also increase alongside the degree of IP .…”

Section: Discussionmentioning

confidence: 99%

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Risk factors associated with intestinal permeability in an adult population: A systematic review

et al. 2019

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Background Increased intestinal permeability (IP) involves the loss of integrity between the cells of the small intestine. IP has been suggested to contribute to the pathogenesis and exacerbation of many chronic diseases. Many potential risk factors for IP are proposed in contemporary literature. The purpose of this review is to identify the most significant risk factors for IP. Methods A systematic search of literature published up until September 2018 in the PubMed, EMBASE, CINAHL, and Scopus databases was conducted. Results A total of 47 articles met the inclusion criteria. Elevated levels of proinflammatory markers, dyslipidaemia, hyperglycaemia, insulin resistance, anthropometric measurements resembling obesity, advanced disease severity, comorbidity and the consumption of a Western‐style diet were identified as the strongest risk factors for altered intestinal integrity. The risk of IP increases when coupled with a multiple disease state or combined with other environmental risk factors. Furthermore, many of the identified risk factors such as anthropometric measurements and biomarkers were external from intestinal health and rather resembled a metabolic‐like condition. Conclusions This review identified a number of potential risk factors for IP, ranging from biomarkers to anthropometric measurements, demographics, dietary intake and chronic diseases. These risk factors warrant the attention of clinicians and other healthcare providers to aid the identification of potential patients at risk of altered IP. Further research needs to examine whether the identified risk factors are homogeneous with the diagnosis of IP or whether the disease state influences the association.

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Low‐grade endotoxemia and platelet activation in cirrhosis

Abstract: LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis. (Hepatology 2017;65:571-581).

Cited by 115 publications

References 33 publications

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

Suboptimal use of pharmacological venous thromboembolism prophylaxis in cirrhotic patients

Risk factors associated with intestinal permeability in an adult population: A systematic review

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