Year: 2024
Type: article
Study design: Observational Study
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.
DOI: 10.1111/apt.18160
Authors: Caroline Conlon, Yi‐Ju Li, Jawad Ahmad, Huiman Barnhart, Robert J. Fontana, Marwan Ghabril, Paul H. Hayashi, David E. Kleiner, William M. Lee, Victor Navarro, Joseph A. Odin, Elizabeth J. Phillips, Andrew Stolz, Raj Vuppalanchi, Dina Halegoua‐DeMarzio, for the Drug‐Induced Liver Injury Network (DILIN)
Institutions: Thomas Jefferson University, Duke Clinical Research Institute, Icahn School of Medicine at Mount Sinai, University of Michigan, Indiana University School of Medicine, United States Food and Drug Administration, National Institutes of Health, National Cancer Institute, The University of Texas Southwestern Medical Center, Thomas Jefferson University Hospital, Jefferson Einstein Philadelphia Hospital, Vanderbilt University Medical Center, University of Southern California
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,250
Funders: Andrea and Charles Bronfman Philanthropies, University of Southern California, Vanderbilt University, Northwestern University, Johns Hopkins University, Broad Institute, Hebrew University of Jerusalem, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Human Genome Research Institute, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: IU Clinical Center: Drug Induced Liver Injury Network, G151959291, Common and Rare Genetic Factors in an Ethnically Homogeneous Schizophrenia Cohort, G249898936, Pooled genome-wide analysis of kidney cancer risk, Coordinating Center for the Drug Induced Liver Injury Network (DILIN), G2888548701, Alzheimer's Disease Patient Registry (ADPR/ACT), G330805887, G38283659, Diverse ancestry biobank to map biomedical traits and elucidate health disparitie, G4503763930, A Center for GEI Association Studies, Genome-Wide Study of Cataract and Low HDL in the Personalized Medicine Research P, JH/CIDR Genotyping for Genome-Wide Association Studies, Mount Sinai Regional Drug Induced Liver Injury Network Site, Vanderbilt Genome-Electronic Records Project, Michigan Hepatotoxicity Clinical Research Network Renewal, Identifying Molecular Subtypes of Schizophrenia: A Novel Genomic Approach, Herbal and Dietary Supplement Induced Liver Injury in the U.S., University of North Carolina Clinical Center for DILIN, USC-UCLA Drug-Induced Liver Injury (DILI) Clinical Center, Drug Induced Liver Injury Network Data Coordinating Center
OpenAlex ID: W4400568203