Low‐grade endotoxemia and platelet activation in cirrhosis
Open accessAbstract
Patients with cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial lipopolysaccharide (LPS) is implicated in platelet activation. In a cross‐sectional study, conducted in an ambulatory care clinic and hospital, comparing 69 cirrhosis patients and 30 controls matched for sex, age, and atherosclerotic risk factors, serum levels of LPS, soluble cluster of differentiation 40 ligand and p‐selectin (two markers of platelet activation), and zonulin (a marker of gut permeability) were investigated. Ex vivo and in vitro studies were also performed to explore the effect of LPS on platelet activation. Compared to controls, cirrhosis patients displayed higher serum levels of LPS (6.0 [4.0‐17.5] versus 57.4 [43.4‐87.2] pg/mL, P < 0.0001), soluble cluster of differentiation 40 ligand (7.0 ± 2.2 versus 24.4 ± 13.3 ng/mL, P < 0.0001), soluble p‐selectin (14.2 ± 4.05 versus 33.2 ± 15.2 ng/mL, P < 0.0001), and zonulin (1.87 ± 0.84 versus 2.54 ± 0.94 ng/mL, P < 0.006). LPS significantly correlated with zonulin (r = 0.45, P < 0.001). Ex vivo studies showed that platelets from cirrhosis patients were more responsive to the agonists independently from platelet count; this phenomenon was blunted by incubation with an inhibitor of Toll‐like receptor 4. In vitro study by normal platelets showed that LPS alone (50‐150 pg/mL) did not stimulate platelets but amplified platelet response to the agonists; Toll‐like receptor 4 inhibitor blunted this effect. Conclusion: LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis. (H epatology 2017;65:571‐581).
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Blood endotoxin levels are elevated during infections, gut inflammation, gum disease, and neurodegenerative disease.
“but are elevated during infections, gut inflammation, gum disease and neurodegenerative disease.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [11]
Peripheral diseases that elevate blood endotoxin, such as sepsis, AIDS and liver failure, also result in neurodegeneration.
“Peripheral diseases that elevate blood endotoxin, such as sepsis, AIDS and liver failure, also result in neurodegeneration.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [11]
Serious liver disease increases peripheral blood endotoxin to potentially toxic levels (60-80 pg/ml in cirrhosis).
“So, serious liver disease increases peripheral blood endotoxin to potentially toxic levels (60–80 pg/ml in cirrhosis) [11, 41].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [11]
Serum endotoxin levels are elevated in patients with severe autism, liver cirrhosis, diabetes, cardiovascular disease, chronic infection and ageing, amyotrophic lateral sclerosis and Alzheimer's disease.
“Serum endotoxin levels are elevated in patients with severe autism [30], liver cirrhosis [11], diabetes [31], cardiovascular disease [8], chronic infection and ageing [32], amyotrophic lateral sclerosis and Alzheimer’s disease [10].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [11]
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- Authors
- Raparelli, V., Basili, S., Carnevale, R., Napoleone, L., Del Ben, M., Nocella, C., Bartimoccia, S., Lucidi, C., Talerico, G., Riggio, O., & Violi, F.
- Affiliations
- Sapienza University of Rome (IT)
- Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy
- Corresponding author
- Violi, Francesco
- ORCID
- Venue
- Hepatology
- Published
- 2016-11-05
- Volume
- 65
- Issue
- 2
- Pages
- 571-581
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2521181071
- Cited by
- 142
- References
- 32
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 11 · 2023: 27 · 2022: 12 · 2021: 17 · 2020: 16 · 2019: 16 · 2018: 15 · 2017: 7 · 2016: 2
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- liver cirrhosis, endotoxemia, lipopolysaccharide, platelet activation, soluble CD40 ligand, P-selectin, zonulin, intestinal permeability, TLR4, thrombotic complications, bacterial endotoxin
- MeSH terms
- Adult, Aged, Cross-Sectional Studies, Female, Humans, Lipopolysaccharides, Liver Cirrhosis, Male, Middle Aged, Platelet Count, Reference Values, Severity of Illness Index, Platelet Activation, Case-Control Studies, Statistics, Nonparametric, P-Selectin, Endotoxemia
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