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. 2023 Jun 22:61:102046.
doi: 10.1016/j.eclinm.2023.102046. eCollection 2023 Jul.

Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study

David Marti-Aguado  1   2 , Amir Gougol  1   3 , Concepcion Gomez-Medina  2 , Arsia Jamali  1 , Abdelrhman Abo-Zed  1 , Dalia Morales-Arraez  4 , Alejandro Jimenez-Sosa  5 , Keith Burns  1 , Aditi Bawa  1 , Anjara Hernández  4 , Claudia Pujol  6 , Edilmar Alvarado-Tapias  1   6   7 , Justyna Szafranska  8 , Wai Kan Chiu  1 , Ares Villagrasa  9 , Meritxell Ventura-Cots  7   9 , Haritha Gandicheruvu  1 , Paloma Lluch  2 , Hui-Wei Chen  10 , Vikrant Rachakonda  11 , Andres Duarte-Rojo  1 , Ramon Bataller  1   12
Affiliations

Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study

David Marti-Aguado et al. EClinicalMedicine. .

Abstract

Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH.

Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]).

Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24).

Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH.

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Keywords: Alcohol use disorder; Alcohol withdrawal syndrome; Alcohol-associated hepatitis; Benzodiazepines.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest regarding this manuscript.

Figures

Fig. 1
Fig. 1
Kaplan Meier curves comparing the survival between different treatment strategies to control Alcohol Withdrawal Syndrome in Alcohol-associated Hepatitis patients. The blue line corresponds to oral benzodiazepines, the green line to intravenous benzodiazepine, and the purple line to phenobarbital. Raw p-values are presented. Abbreviations: IV, Intravenous; AWS, Alcohol withdrawal syndrome.
Fig. 2
Fig. 2
Kaplan–Meier curve comparing survival between patients with (green line) and without (blue line) Alcohol Withdrawal Syndrome during hospitalization for Alcohol-associated Hepatitis. Raw p-values are presented. Abbreviations: AWS, Alcohol withdrawal syndrome.
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