Effects of prazosin treatment on liver enzymes are moderated by alcohol withdrawal symptoms in individuals with alcohol use disorder.

alcohol use disorder alcohol withdrawal aspartate transaminase gamma-glutamyltransferase prazosin

Journal

Alcohol, clinical & experimental research
ISSN: 2993-7175
Titre abrégé: Alcohol Clin Exp Res (Hoboken)
Pays: United States
ID NLM: 9918609780906676

Informations de publication

Date de publication:
23 Jan 2024
Historique:
revised: 19 12 2023
received: 09 10 2023
accepted: 23 12 2023
medline: 23 1 2024
pubmed: 23 1 2024
entrez: 23 1 2024
Statut: aheadofprint

Résumé

Alcohol use disorder (AUD) is associated with significant liver pathology marked by elevated liver enzymes. Prazosin, an alpha1-noradrenergic antagonist significantly improves alcohol drinking outcomes in individuals with alcohol withdrawal symptoms (AW), but effects on liver enzymes are unknown. We assessed the effects of prazosin treatment on the liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), and gamma-glutamyltransferase (GGT) in individuals with AUD. Participants (N=100) with AUD were enrolled in a 12-week randomized controlled trial and received either placebo or 16 mg/day of prazosin. Whole blood was drawn from 92 participants to measure liver enzyme levels every 4 weeks, and severity of AW was assessed weekly. Analysis predicting liver function outcomes used linear mixed effects models. Controlling for alcohol consumption, a significant AW × treatment effect was seen for ALT (p < 0.05), AST (p < 0.05) and GGT (p < 0.01). Additionally, AST (b = 0.2, p < 0.01), ALT (b = 0.2, p < 0.05), and GGT (b = 0.3, p < 0.01) were elevated in individuals with higher AW in the placebo but not in the prazosin group (AST: p > 0.66; ALT: p > 0.65). Only in the prazosin group were lower GGT levels associated with higher withdrawal severity (b = -0.16, p < 0.05). We found an interaction of alcohol withdrawal symptoms and prazosin treatment on liver enzyme levels, which were not influenced by week in the trial or the amount of alcohol consumed. Together, these findings suggest that prazosin treatment reduces liver enzymes over the course of AUD treatment among individuals with significant AW, though replication to establish clinical utility is needed.

Sections du résumé

BACKGROUND BACKGROUND
Alcohol use disorder (AUD) is associated with significant liver pathology marked by elevated liver enzymes. Prazosin, an alpha1-noradrenergic antagonist significantly improves alcohol drinking outcomes in individuals with alcohol withdrawal symptoms (AW), but effects on liver enzymes are unknown. We assessed the effects of prazosin treatment on the liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), and gamma-glutamyltransferase (GGT) in individuals with AUD.
METHODS METHODS
Participants (N=100) with AUD were enrolled in a 12-week randomized controlled trial and received either placebo or 16 mg/day of prazosin. Whole blood was drawn from 92 participants to measure liver enzyme levels every 4 weeks, and severity of AW was assessed weekly. Analysis predicting liver function outcomes used linear mixed effects models.
RESULTS RESULTS
Controlling for alcohol consumption, a significant AW × treatment effect was seen for ALT (p < 0.05), AST (p < 0.05) and GGT (p < 0.01). Additionally, AST (b = 0.2, p < 0.01), ALT (b = 0.2, p < 0.05), and GGT (b = 0.3, p < 0.01) were elevated in individuals with higher AW in the placebo but not in the prazosin group (AST: p > 0.66; ALT: p > 0.65). Only in the prazosin group were lower GGT levels associated with higher withdrawal severity (b = -0.16, p < 0.05).
CONCLUSIONS CONCLUSIONS
We found an interaction of alcohol withdrawal symptoms and prazosin treatment on liver enzyme levels, which were not influenced by week in the trial or the amount of alcohol consumed. Together, these findings suggest that prazosin treatment reduces liver enzymes over the course of AUD treatment among individuals with significant AW, though replication to establish clinical utility is needed.

Identifiants

pubmed: 38258493
doi: 10.1111/acer.15263
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIMH NIH HHS
ID : R25MH071584-14
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01-AA020504
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01-AA029113
Pays : United States

Informations de copyright

© 2024 Research Society on Alcohol.

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Auteurs

Bradford S Martins (BS)

Yale Stress Center, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

Nia Fogelman (N)

Yale Stress Center, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

Marshall Tate (M)

Yale Stress Center, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

Gretchen H Hermes (GH)

Yale Stress Center, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

Rajita Sinha (R)

Yale Stress Center, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

Classifications MeSH