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Journal article
Clinical characteristics and HLA associations of azithromycin-induced liver injury
Alimentary pharmacology & therapeutics, Vol.60(6), pp.787-795
2024
PMID: 38988034
Abstract
Background
Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ.
Methods
The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases.
Results
Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively).
Conclusion
Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.
Details
- Title
- Clinical characteristics and HLA associations of azithromycin-induced liver injury
- Authors/Creators
- Caroline Conlon - Thomas Jefferson UniversityYi-Ju Li - Duke Clinical Research Institute, Durham, North Carolina, USAJawad Ahmad - Icahn School of Medicine at Mount SinaiHuiman Barnhart - Clinical Research InstituteRobert J Fontana - University of MichiganMarwan Ghabril - Indiana University School of MedicinePaul H Hayashi - United States Food and Drug AdministrationDavid E Kleiner - National Institutes of HealthWilliam M Lee - The University of Texas Southwestern Medical CenterVictor Navarro - Thomas Jefferson University HospitalJoseph A Odin - Icahn School of Medicine at Mount SinaiElizabeth J Phillips - Vanderbilt University Medical CenterAndrew Stolz - University of Southern CaliforniaRaj Vuppalanchi - Indiana University School of MedicineDina Halegoua-DeMarzio - Thomas Jefferson UniversityDrug‐Induced Liver Injury Network (DILIN)
- Publication Details
- Alimentary pharmacology & therapeutics, Vol.60(6), pp.787-795
- Publisher
- John Wiley & Sons Ltd.
- Grant note
- U01 DK065211 / NIDDK NIH HHS U01DK083020 / NIDDK NIH HHS U01 HG004608 / NHGRI NIH HHS U01 HG007417 / NHGRI NIH HHS U01 DK065176 / NIDDK NIH HHS U24DK065176 / NIDDK NIH HHS U01 DK083020 / NIDDK NIH HHS U01DK100928 / NIDDK NIH HHS U01 DK100928 / NIDDK NIH HHS U01 HG004438 / NHGRI NIH HHS
- Identifiers
- 991005884936707891
- Copyright
- © 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
- Murdoch Affiliation
- Research and Innovation Office; Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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