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Cannabinoids and Chronic Liver Diseases.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.

SUBMITTER: Mboumba Bouassa RS

PROVIDER: S-EPMC9408890 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Cannabinoids and Chronic Liver Diseases.

Mboumba Bouassa Ralph-Sydney RS Sebastiani Giada G Di Marzo Vincenzo V Jenabian Mohammad-Ali MA Costiniuk Cecilia T CT

International journal of molecular sciences 20220820 16

Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflamma ...[more]

PMID: 36012687

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Project description:Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT < 100, 109/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.

Dataset Information

Cannabinoids and Chronic Liver Diseases.

Publications

Cannabinoids and Chronic Liver Diseases.

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