Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism
Abstract 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 investigat...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Environmental Health |
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| Online Access: | https://doi.org/10.1186/s12940-024-01054-6 |
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| author | Moana Gelu-Simeon Marie-Josée Lafrance Leah Michineau Eric Saillard Jean Pierre Thomé Claude Emond Michel Samson Luc Multigner |
| author_facet | Moana Gelu-Simeon Marie-Josée Lafrance Leah Michineau Eric Saillard Jean Pierre Thomé Claude Emond Michel Samson Luc Multigner |
| author_sort | Moana Gelu-Simeon |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T19:53:09Z |
| format | Article |
| id | doaj.art-b945bc8718214513b54b987e4d66ef1d |
| institution | Directory Open Access Journal |
| issn | 1476-069X |
| language | English |
| last_indexed | 2024-04-24T19:53:09Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Environmental Health |
| spelling | doaj.art-b945bc8718214513b54b987e4d66ef1d2024-03-24T12:32:33ZengBMCEnvironmental Health1476-069X2024-03-012311910.1186/s12940-024-01054-6Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolismMoana Gelu-Simeon0Marie-Josée Lafrance1Leah Michineau2Eric Saillard3Jean Pierre Thomé4Claude Emond5Michel Samson6Luc Multigner7CHU de la Guadeloupe, Univ Antilles, Inserm, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire de GuadeloupeUniv Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire de GuadeloupeUniversité de Liège, LEAE -CART, Freshwater and Oceanic Sciences Unit of Research (FOCUS)PKSH IncUniv Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085Abstract 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.https://doi.org/10.1186/s12940-024-01054-6ChlordeconePersistent organic pollutantsLiver fibrosisReverse causality |
| spellingShingle | Moana Gelu-Simeon Marie-Josée Lafrance Leah Michineau Eric Saillard Jean Pierre Thomé Claude Emond Michel Samson Luc Multigner Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism Environmental Health Chlordecone Persistent organic pollutants Liver fibrosis Reverse causality |
| title | Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism |
| title_full | Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism |
| title_fullStr | Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism |
| title_full_unstemmed | Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism |
| title_short | Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism |
| title_sort | inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis the role of liver metabolism |
| topic | Chlordecone Persistent organic pollutants Liver fibrosis Reverse causality |
| url | https://doi.org/10.1186/s12940-024-01054-6 |
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