Clinical and HLA Associations of Fluoroquinolone-Induced Liver Injury: Results From the Drug-Induced Liver Injury Network
Jawad Ahmad, Andrew Dellinger, Paola Nicoletti, Huiman X. Barnhart, Marwan Ghabril, Robert J. Fontana, Victor J. Navarro, Gina Choi, Paul H. Hayashi, Jiezhun Gu, David E. Kleiner, Drug-Induced Liver Injury Network
Abstract
INTRODUCTION: 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 DILI Network between 2004 and 2022. HLA class I and II alleles were sequenced by the Illumina MiSeq platform. RESULTS: Sixty-one 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 2-1,370) 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% because of liver failure). Two HLA alleles were associated with an increased risk of liver injury: HLA-DQA1*03:01 (carriage frequency 38% in cases vs 19% in controls) and HLA B*57:01 (15% vs 6%). There was a significant difference between the combined carriage frequency of the 2 alleles of 48% in cases vs 24% controls ( P = 0.0001). No clinical characteristics or outcomes were associated with carriers compared with noncarriers. DISCUSSION: 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 .