Genetic factors influencing drug induced liver injury: do they have a role in prevention and diagnosis?

Kathleen E. Clare, Michael H. Miller, John F. Dillon (Lead / Corresponding author)

    Research output: Contribution to journalReview articlepeer-review

    23 Citations (Scopus)
    200 Downloads (Pure)

    Abstract

    Purpose of review: The pathogenesis of DILI is currently unknown however research has shown strong genetic associations with some DILIs. This paper describes the variant alleles uncovered by GWAS and discusses their potential role as susceptibility biomarkers.

    Recent findings: An association with HLADRB1*15:01 and amoxicillin/clavulanate DILI has been shown by a number of research groups. The presence of the HLA-B*57:01 allele has been associated with an 81-fold increased risk of flucloxacillin DILI. The HLA-B*35:02 allele has significant association with minocycline DILI.

    Summary: With the exception of abacavir for HIV therapy, no other prospective genetic screening tests have met the threshold for clinical application. This is largely because DILI incidence is too low to warrant the cost and effort associated with testing. Perhaps, with the development of personalised medicine, a panel of genes for disease susceptibility, drug efficacy and adverse reactions could be tested once off. This would change the cost effectiveness paradigm, personalise healthcare and reduce DILI risk by avoiding medications in patients with specific HLA alleles.
    Original languageEnglish
    Pages (from-to)258-264
    Number of pages7
    JournalCurrent Hepatology Reports
    Volume16
    Issue number3
    Early online date7 Aug 2017
    DOIs
    Publication statusPublished - Sept 2017

    Keywords

    • Drug induced liver injury
    • genetic association
    • biomarker
    • predisposition: amoxicillin/clavulanate
    • flucloxacillin

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