Clinical and HLA associations of fluoroquinolone induced liver injury: results from the Drug-Induced Liver Injury Network

Background and Aims: Fluoroquinolones (FQ) have a favorable safety profile, but the risk of drug-induced liver injury (DILI) is well described. The aim of this study was to identify clinical features and HLA genetic variants associated with FQ-DILI in a large national registry. Methods: Analysis of FQ-DILI cases enrolled in DILIN between 2004-2022. HLA class I and II alleles were sequenced by the Illumina MiSeq platform. Results: 61 cases (32 ciprofloxacin, 22 levofloxacin, 7 moxifloxacin) were included. Clinical features between the 3 drugs were similar. The median duration of therapy was 7 (range 2-54) days; median age 53 (range 22-80) years; and 67% were female. Median latency to onset was 12 (range 2-1370) days with 44% hepatocellular, 30% mixed, and 26% cholestatic pattern of liver injury. Median time to recovery was 65 days, but 13% had persistent injury at 6 months, 15% died (11% due to liver failure). Two HLA alleles were associated with an increased risk of liver injury: HLA-DQA1*03:01 (carriage frequency (CF) 38% in cases vs 19% in controls) and HLA B*57:01 (15% vs 6%). There was a significant difference between the combined CF of the 2 alleles of 48% in cases vs 24% controls, (p = 0.0001). No clinical characteristics or outcomes were associated with carriers compared to non-carriers. Conclusion: FQ DILI is a class effect that presents with a short latency, variable pattern of liver injury, and carries a significant risk of chronicity and mortality. There is a significant association with HLA-DQA1*03:01 and HLA B*57:01 .