The Role of Intestinal Endotoxin in Liver Injury: A Long and Evolving History
Open accessAbstract
From the mid-1950s, it was observed that liver injury by a variety of toxins greatly sensitized the host to the effects of administered lipopolysaccharide. In the nutritional cirrhosis of choline deficiency, and in acute toxic injury as well, the need for the presence of enteric endotoxin was demonstrated. The universality of this association was striking for almost all agents associated with liver injury. In addition, the presence of endotoxemia in human liver disease was documented in the 1970s, when the hypothesis was first proposed, and correlated with the severity of the disease. Despite imposing evidence of the critical role of enteric endotoxin in liver injury, it did not excite much interest in investigators until the 1980s. With the ability to study effects of alcohol in newer delivery systems, and an increased understanding of the role of Kupffer cells in the process, the original hypothesis has been accepted. This historical review details the progress of this novel concept of disease initiation and suggests future directions to bring potential therapies to the bedside. (Hepatology 2010.)
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High circulating lipopolysaccharide levels in mice and patients with chronic liver disease and hepatocellular carcinoma demonstrate a leaky gut during multiple stages of chronic liver disease and hepatocarcinogenesis.
“High circulating LPS levels in mice and patients with CLD as well as in HCC14,24,77,78 demonstrate the presence of a leaky gut during multiple stages of CLD and hepatocarcinogenesis (FIG. 1).”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [78]
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- Authors
- Nolan, J. P.
- Affiliations
- State University of New York (US)
- Corresponding author
- Nolan, James P.
- ORCID
- Nolan, James P.
- Venue
- Hepatology
- Published
- 2010-11
- Volume
- 52
- Issue
- 5
- Pages
- 1829-1835
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2028042832
- Cited by
- 229
- References
- 45
- Citations by year
- 2025: 12 · 2024: 9 · 2023: 5 · 2022: 17 · 2021: 20 · 2020: 15 · 2019: 18 · 2018: 18 · 2017: 20 · 2016: 19 · 2015: 18 · 2014: 11 · 2013: 17 · 2012: 14
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- intestinal endotoxin, lipopolysaccharide, liver injury, endotoxemia, Kupffer cells, alcohol-induced liver injury, liver disease severity
- MeSH terms
- Animals, Disease Models, Animal, Endotoxins, Humans, Kupffer Cells, Lipopolysaccharides, Mononuclear Phagocyte System, Chemical and Drug Induced Liver Injury
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