Research Article Details
| Article ID: | A26313 |
| PMID: | 20661154 |
| Source: | J Clin Gastroenterol |
| Title: | Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis. |
| Abstract: | BACKGROUND: Endotoxin is hypothesized to play an important role in the activation of inflammatory pathways associated with nonalcoholic steatohepatitis (NASH). However, demonstration of hepatic endotoxin exposure is challenging due to the inaccessibility of the portal circulation. Furthermore, reliable measurement of the relatively low endotoxin levels in plasma of patients with liver disease and subsequent interpretation remain difficult. GOALS: In this study, we used the EndoCab assay that measures endogenous antibodies to the core region of endotoxin to estimate hepatic endotoxin exposure over time. STUDY: IgG levels against endotoxin were measured in peripheral plasma obtained from 21 severely obese patients with NASH and 9 severely obese patients with healthy livers. RESULTS: Plasma IgG levels against endotoxin were significantly elevated in patients with NASH compared with patients with healthy livers (48±63 GMU/mL vs. 10±13 GMU/mL). Moreover, these IgG levels progressively increased with NASH grade (grade 1 29±37; grade 2 58±51; grade 3 84±132 GMU/mL, P<0.05). There was no relation between plasma IgG levels and NASH stage. CONCLUSIONS: Plasma IgG levels against endotoxin were found to be increased in biopsy-proven human NASH and increased with aggravated inflammation in NASH, suggesting a relationship between chronic endotoxin exposure and the severity of human NASH. |
| DOI: | 10.1097/MCG.0b013e3181e12c24 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |