Ahmad Jawad, Dellinger Andrew, Nicoletti Paola, Barnhart Huiman X, Ghabril Marwan, Fontana Robert J, Navarro Victor, Choi Gina, Hayashi Paul H, Gu Jiezhun, Kleiner David
Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Duke School of Medicine, Durham, North Carolina, USA.
Am J Gastroenterol. 2025 Apr 10. doi: 10.14309/ajg.0000000000003457.
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.
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.
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-DQA103:01 (carriage frequency 38% in cases vs 19% in controls) and HLA B57:01 (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.
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-DQA103:01 and HLA B57:01 .
氟喹诺酮类药物（FQ）具有良好的安全性，但药物性肝损伤（DILI）的风险已有详尽描述。本研究的目的是在一个大型国家登记处中确定与FQ-DILI相关的临床特征和HLA基因变异。
分析2004年至2022年期间纳入药物性肝损伤网络的FQ-DILI病例。通过Illumina MiSeq平台对HLA I类和II类等位基因进行测序。
共纳入61例病例（32例环丙沙星、22例左氧氟沙星、7例莫西沙星）。这三种药物的临床特征相似。治疗的中位持续时间为7（范围2 - 54）天，中位年龄53（范围22 - 80）岁，67%为女性。发病的中位潜伏期为12（范围2 - 1370）天，肝损伤模式为肝细胞型44%、混合型30%、胆汁淤积型26%。恢复的中位时间为65天，但13%在6个月时仍有持续性损伤，15%死亡（11%因肝衰竭）。两个HLA等位基因与肝损伤风险增加相关：HLA-DQA103:01（病例携带频率38%，对照为19%）和HLA B57:01（15% vs 6%）。病例中这两个等位基因的联合携带频率为48%，对照为24%，差异有统计学意义（P = 0.0001）。与非携带者相比，携带者的临床特征或结局无差异。
FQ-DILI是一种类效应，潜伏期短，肝损伤模式多样，具有显著的慢性化和死亡风险。与HLA-DQA103:01和HLA B57:01存在显著关联。
