Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism.

Autor: Gelu-Simeon M; CHU de la Guadeloupe, Univ Antilles, Inserm, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Route de Chauvel, Pointe-à-Pitre Cedex, Guadeloupe, 97159, France. moana.simeon@chu-guadeloupe.fr.; Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Guadeloupe, Pointe à Pitre, Guadeloupe, France. moana.simeon@chu-guadeloupe.fr., Lafrance MJ; Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Guadeloupe, Pointe à Pitre, Guadeloupe, France., Michineau L; Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Avenue du Professeur Léon Bernard, Rennes, F-35000, France., Saillard E; Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Guadeloupe, Pointe à Pitre, Guadeloupe, France., Thomé JP; Université de Liège, LEAE -CART, Freshwater and Oceanic Sciences Unit of Research (FOCUS), B6C, Liège, 4000, Belgium., Emond C; PKSH Inc, Crabtree, QC, Canada.; École de Santé Publique, Département de Santé Environnementale et Santé au Travail (DSEST), Université de Montréal, Montreal, QC, Canada., Samson M; Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Avenue du Professeur Léon Bernard, Rennes, F-35000, France. michel.samson@inserm.fr., Multigner L; Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Avenue du Professeur Léon Bernard, Rennes, F-35000, France.
Jazyk: angličtina
Zdroj: Environmental health : a global access science source [Environ Health] 2024 Mar 20; Vol. 23 (1), pp. 30. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1186/s12940-024-01054-6
Abstrakt: Background and Aims: Chlordecone is a persistent organochlorinated insecticide, extensively used in the French West Indies and has been contaminating the population for more than thirty years. Its potentiation effect on hepatotoxic agents has been demonstrated in animal models. We investigated the relationship between environmental exposure to chlordecone and the progression of liver fibrosis.
Methods: This study included 182 consecutive patients with chronic alcoholic hepatitis whose liver fibrosis was assessed using non-invasive methods. Measured plasma chlordecone concentrations at inclusion were used as surrogate of long-term exposure under steady-state conditions. As the pharmacokinetic processing of chlordecone is largely determined by the liver, we used a human physiologically based pharmacokinetic model to predict plausible changes in the steady-state blood chlordecone concentrations induced by liver fibrosis.
Results: With a median follow-up of 27.1 years after the onset of alcohol consumption, we found a significant decrease in the risk of advanced liver fibrosis with increasing plasma chlordecone concentration (adjusted hazard ratio = 0.56; 95% confidence interval: 0.34-0.95 for the highest vs. lowest tertile, p = 0.04). Changes induced by liver fibrosis influenced the pharmacokinetic processing of chlordecone, resulting in substantial modifications in its steady-state blood concentrations.
Conclusion: According to this human model of coexposure to alcohol, reverse causality is the most plausible explanation of this inverse association between plasma chlordecone concentrations and progression of liver fibrosis. This study underlines the importance of considering the pharmacokinetic of environmental contaminants in epidemiological studies when biomarkers of exposure are used to investigate their own impact on the liver.
Trial Registration: ClinicalTrials.gov Identifier: NCT03373396.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje