%0 Journal Article
%T Clinical characteristics and HLA associations of azithromycin-induced liver injury.
%A Conlon C
%A Li YJ
%A Ahmad J
%A Barnhart H
%A Fontana RJ
%A Ghabril M
%A Hayashi PH
%A Kleiner DE
%A Lee WM
%A Navarro V
%A Odin JA
%A Phillips EJ
%A Stolz A
%A Vuppalanchi R
%A Halegoua-DeMarzio D
%A  
%J Aliment Pharmacol Ther
%V 60
%N 6
%D 2024 Sep 10
%M 38988034
%F 9.524
%R 10.1111/apt.18160
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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).<BR><B>CONCLUSIONS: </B>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.