Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA-Update with genetic correlations
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
OBJECTIVE: To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI.
METHODS: In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort.
RESULTS: Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac.
CONCLUSIONS: Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Liver international : official journal of the International Association for the Study of the Liver - (2024) vom: 07. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bonkovsky, Herbert L [VerfasserIn] |
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| Links: |
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| Themen: |
Diclofenac |
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| Anmerkungen: |
Date Revised 07.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/liv.15892 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369407962 |
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| 041 | |a eng | ||
| 100 | 1 | |a Bonkovsky, Herbert L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA-Update with genetic correlations |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 07.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a OBJECTIVE: To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI | ||
| 520 | |a METHODS: In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort | ||
| 520 | |a RESULTS: Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac | ||
| 520 | |a CONCLUSIONS: Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HLA (human leucocyte antigen) | |
| 650 | 4 | |a diclofenac | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a ibuprofen | |
| 650 | 4 | |a idiosyncratic drug-induced liver injury | |
| 650 | 4 | |a immune-mediated liver disease | |
| 700 | 1 | |a Ghabril, Marwan |e verfasserin |4 aut | |
| 700 | 1 | |a Nicoletti, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Dellinger, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Fontana, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a Barnhart, Huiman |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Jiezhun |e verfasserin |4 aut | |
| 700 | 1 | |a Daly, Ann K |e verfasserin |4 aut | |
| 700 | 1 | |a Aithal, Guruprasad P |e verfasserin |4 aut | |
| 700 | 1 | |a Phillips, Elizabeth J |e verfasserin |4 aut | |
| 700 | 1 | |a Kleiner, David E |e verfasserin |4 aut | |
| 700 | 0 | |a US DILIN Investigators |e verfasserin |4 aut | |
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