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; Amir Gougol; Concepcion Gomez-Medina; Arsia Jamali; Abdelrhman Abo-Zed; Dalia Morales-Arraez; Alejandro Jimenez-Sosa; Keith Burns; Aditi Bawa; Anjara Hernández; Claudia Pujol; Edilmar Alvarado-Tapias; Justyna Szafranska; Wai Kan Chiu; Ares Villagrasa; Meritxell Ventura-Cots; Haritha Gandicheruvu; Paloma Lluch; Hui-Wei Chen; Vikrant Rachakonda; Andres Duarte-Rojo; Ramon Bataller

doi:10.1016/j.eclinm.2023.102046

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

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

Authors

David Marti-Aguado^{1

2}, Amir Gougol^{1

3}, Concepcion Gomez-Medina², Arsia Jamali¹, Abdelrhman Abo-Zed¹, Dalia Morales-Arraez⁴, Alejandro Jimenez-Sosa⁵, Keith Burns¹, Aditi Bawa¹, Anjara Hernández⁴, Claudia Pujol⁶, Edilmar Alvarado-Tapias^{1

6

7}, Justyna Szafranska⁸, Wai Kan Chiu¹, Ares Villagrasa⁹, Meritxell Ventura-Cots^{7

9}, Haritha Gandicheruvu¹, Paloma Lluch², Hui-Wei Chen¹⁰, Vikrant Rachakonda¹¹, Andres Duarte-Rojo¹, Ramon Bataller^{1

12}

Affiliations

¹ Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
² Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain.
³ University of California, San Francisco (UCSF), San Francisco, CA, USA.
⁴ Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain.
⁵ Statistical Consultant Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.
⁶ Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Institut de Recerca Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain.
⁷ Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
⁸ Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁹ Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁰ Allegheny General Hospital, Pittsburgh, PA, USA.
¹¹ University of California, Davis, CA, USA.
¹² Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

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.