Human leukocyte antigen (HLA) and other genetic risk factors in drug-induced liver injury (DILI)

Daly, AK

doi:10.1007/978-1-4939-7677-5_24

Human leukocyte antigen (HLA) and other genetic risk factors in drug-induced liver injury (DILI)

Lookup NU author(s): Professor Ann Daly ORCiD

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Abstract

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Genetic risk factors, especially HLA alleles, have been investigated widely as risk factors for DILI development. The earlier studies prior to approx. the year of 2000 suffered from a number of problems including small numbers, imprecise phenotype and limited approaches to genotype or phenotype determination. Development of national and international networks to study DILI has resulted in larger numbers of cases being recruited. In combination with development of standardized methods for causality assessment and the introduction of genome-wide association studies (GWAS) in place of the earlier candidate gene approaches, this has resulted in more consistent findings on genetic risk factors. The newer studies using GWAS have confirmed the importance of HLA alleles as risk factors for DILI and have demonstrated that while particular HLA alleles are specific to individual drug causes of DILI, some unrelated drugs show similar HLA associations. Importantly, not all forms of DILI show HLA associations, and polymorphisms in other genes, especially those relevant to drug disposition, protection against oxidative stress and the innate immune system may also be relevant to risk of DILI. Identification of additional genetic risk factors may be feasible but will require larger case numbers than those currently available. The positive predictive value of all genetic risk factors discovered to date is low, but there is potential to combine genetic data with additional patient data such as age and gender to assess the risk of developing DILI with certain drugs.