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. 2024 Jan 1;119(1):200-202.
doi: 10.14309/ajg.0000000000002454. Epub 2023 Aug 8.

HLA-B*53:01 Is a Significant Risk Factor of Liver Injury due to Phenytoin and Other Antiepileptic Drugs in African Americans

Paola Nicoletti  1 , Andrew Dellinger  2 , Yi-Ju Li  2 , Huiman Barnhart  3 , Elizabeth Phillips  4 , Naga Chalasani  5 ; Drug Induced Liver Injury Network (DILIN) investigators
Affiliations

HLA-B*53:01 Is a Significant Risk Factor of Liver Injury due to Phenytoin and Other Antiepileptic Drugs in African Americans

Paola Nicoletti et al. Am J Gastroenterol. .

Abstract

Introduction: To investigate human leukocyte antigen alleles associated with liver injury due to antiepileptic drugs (AEDs) in African Americans (AA).

Methods: In this study, 21 AA with AED drug-induced liver injury (DILI), 176 AA with DILI due to non-AEDs, and 5816 AA population controls were included.

Results: HLA-B*53:01 was significantly associated with aromatic AED-DILI (odds ratio: 4.52, 95% confidence interval: 2.42-8.44, P = 1.46 × 10 -5 ). Phenytoin DILI showed the strongest association with HLA-B*53:01 (odds ratio: 9.17; 95% confidence interval: 3.61-23.28, P = 1.1 × 10 -5 ). The HLA-B*53:01 allele was carried by 8 of 9 AA phenytoin DILI cases.

Discussion: HLA-B*53:01 is a significant risk factor of liver injury due to antiepileptics, particularly phenytoin, in AA.

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Conflict of interest statement

Disclosures: Dr. Chalasani has ongoing paid consulting activities (or had in preceding 12 months) with Madrigal, Foresite labs, Galectin, Zydus, Glaxo Smith Kline, Merck, Pfizer and Altimmune. He has grant support from Exact Sciences and DSM. These activities are not directly or significantly related to this paper. Dr. Nicoletti has ongoing paid consulting activities with Astella and Chiesi Farmaceutici. Dr. Phillips receives Royalties from UpToDate and consulting fees from Janssen, Vertex, Biocryst, Regeneron, AstraZeneca and Verve. She is co-director of IIID Pty Ltd that holds a patent for HLA-B*57:01 testing for abacavir hypersensitivity and has a patent pending for Detection of Human Leukocyte Antigen-A*32:01 in connection with Diagnosing Drug Reaction with Eosinophilia and Systemic Symptoms for vancomycin without any financial remuneration and not directly related to the submitted work. Drs. Barnhart, Dellinger, and Li have no conflicts of interests to disclose.

Comment in

References

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    1. Mullan KA, Anderson AL, Illing PT, et al. HLA-associated antiepileptic drug-induced cutaneous adverse reactions. HLA 2019; 93: 417–435. - PubMed
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    1. Hoofnagle JH, Bonkovsky HL, Phillips EJ, et al. HLA-B*35:01 and green tea-induced liver injury. Hepatology 2021; 73: 2484–2493 - PMC - PubMed

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