Conlon, CarolineLi, Yi-JuAhmad, JawadBarnhart, HuimanFontana, Robert J.Ghabril, MarwanHayashi, Paul H.Kleiner, David E.Lee, William M.Navarro, VictorOdin, Joseph A.Phillips, Elizabeth J.Stolz, AndrewVuppalanchi, RajHalegoua-DeMarzio, DinaDrug-Induced Liver Injury Network (DILIN)2024-12-112024-12-112024Conlon C, Li YJ, Ahmad J, et al. Clinical characteristics and HLA associations of azithromycin-induced liver injury. Aliment Pharmacol Ther. 2024;60(6):787-795. doi:10.1111/apt.18160https://hdl.handle.net/1805/44925Background: 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.en-USPublisher PolicyDrug-induced liver injuryCausalityChronic liver injuryAlleleArticle