Clinical characteristics and HLA associations of azithromycin-induced liver injury.

Autor: Conlon C; Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Li YJ; Duke Clinical Research Institute, Durham, North Carolina, USA., Ahmad J; Icahn School of Medicine at Mount Sinai, New York, New York, USA., Barnhart H; Duke Clinical Research Institute, Durham, North Carolina, USA., Fontana RJ; University of Michigan Medical School, Ann Arbor, Michigan, USA., Ghabril M; Indiana University School of Medicine, Indianapolis, Indiana, USA., Hayashi PH; Division of Hepatology and Nutrition, Food and Drug Administration, Silver Spring, Maryland, USA., Kleiner DE; National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Lee WM; University of Texas Southwestern Medical Center, Dallas, Texas, USA., Navarro V; Jefferson Health, Einstein Medical Center, Philadelphia, Pennsylvania, USA., Odin JA; Icahn School of Medicine at Mount Sinai, New York, New York, USA., Phillips EJ; Vanderbilt University Medical Center, Nashville, Tennessee, USA., Stolz A; University of Southern California Keck School of Medicine, Los Angeles, California, USA., Vuppalanchi R; Indiana University School of Medicine, Indianapolis, Indiana, USA., Halegoua-DeMarzio D; Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2024 Sep; Vol. 60 (6), pp. 787-795. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1111/apt.18160
Abstrakt: 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.
(© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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