| Title: |
HLA‐B*44 Alleles and HLA‐DQA1*03:01 as Genetic Risk Factors for Drug‐Induced Liver Injury due to Fluoroquinolones. |
| Authors: |
Nicoletti, Paola; Lucena, M. Isabel; Andrade, Raul J.; Zafer, Samreen; Bjornsson, Einar S.; Hallberg, Pär; Larrey, Dominique; Molokhia, Mariam; Wadelius, Mia; Aithal, Guruprasad P.; Daly, Ann K. |
| Source: |
Liver International; Jun2026, Vol. 46 Issue 6, p1-9, 9p |
| Subject Terms: |
Histocompatibility class I antigens; Fluoroquinolones; HLA-DR antigens; Ciprofloxacin; Immunogenetics; Genetic risk score; Hepatotoxicology; Europeans |
| Abstract: |
Background and Aims: Fluoroquinolone exposure can give rise to drug‐induced liver injury. Genetic risk factors for this form of liver injury are poorly understood but some evidence suggests that HLA genes contribute. This study aimed to characterise HLA risk factors for fluoroquinolone‐induced liver injury in a European population. Methods: From the previously described iDILIC cohort, 22 cases of fluoroquinolone‐induced liver injury were identified, with most cases (n = 13) related to ciprofloxacin. Liver injury cases due to other drugs (n = 458), also from iDILIC, served as controls. HLA genotypes were imputed from genome‐wide association analysis data using SNPtoHLA. Frequency differences between cases and controls for HLA alleles, HLA amino acids and HLA families were assessed by applying a logistic regression model. Results: HLA‐significant associations were detected for HLA class I and II alleles with individual allelic associations detected for HLA‐B*44:03, HLA‐A*29:02, HLA‐C*16:01, HLA‐DQA1*03:01 and several HLA‐DRB1 alleles. Combined HLA‐B*44 alleles were associated with DILI with an odds ratio of 5.33 [95% confidence interval 2.45–11.61; p = 2.5 × 10−5]. Serine at position‐167 in HLA‐B, specific to B*44:02, B*44:03 and B*45:01, was associated with a significantly increased risk of liver injury (p = 4.7 × 10−6), but no other HLA‐B amino acids were significant. The B*44 association was also significant among ciprofloxacin cases only. Conclusions: A novel HLA‐B*44 association with fluoroquinolone‐induced liver injury has been identified and a previously reported but weaker association with HLA‐DQA1*03:01 confirmed. The B*44 findings suggest a mechanism involving inappropriate recognition of drug‐modified self peptides by serine‐167 in pocket A of the HLA‐B protein. Lay Summary: Fluoroquinolone antimicrobials may cause drug‐induced liver injury. This study describes the clinical characteristics of a European cohort involving 22 cases who developed drug‐induced liver injury after exposure to various fluoroquinolones. Certain HLA genotypes increase the risk of developing this adverse drug reaction. [ABSTRACT FROM AUTHOR] |
| : |
Copyright of Liver International is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |