692
Views
19
CrossRef citations to date
0
Altmetric
Review

Genetic risk factors in the development of idiosyncratic drug-induced liver injury

, &
Pages 153-169 | Received 29 Aug 2020, Accepted 19 Nov 2020, Published online: 14 Dec 2020

References

  • Andrade RJ, Chalasani N, Björnsson ES, et al. Drug-induced liver injury. Nat Rev Dis Primers. 2019;5(1):58.
  • Sgro C, Clinard F, Ouazir K, et al. Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology. 2002;36(2):451–455.
  • Björnsson ES, Bergmann OM, Björsson HK, et al. Incidence, presentation, and outcome in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144(7):1419–1425.
  • Reuben A, Koch DG, Lee WM, et al. Drug-induced acute liver failure: results of a U. S. multicentre prospective study. Hepatology. 2010;52(6):2065–2076.
  • LiverTox: Clinical and research information on drug-induced liver injury. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548196/ (accessed 2020 April 23)
  • Lucena MI, Andrade RJ, Kaplowitz N, et al. Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex. Hepatology. 2009;49(6):2001–2009.
  • Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcome of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–1352.
  • Devarbhavi H, Dierkhising R, Kremers WK, et al. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105(11):2396–2404.
  • Rathi C, Pipaliya N, Patel R, et al. Drug induced liver injury at a tertiary hospital in India: etiology, clinical features and predictors of mortality. Ann Hepatol. 2017;16(3):442–450.
  • Shen T, Liu Y, Shang J, et al. Incidence and etiology of drug-induced liver injury in mainland China. Gastroenterology. 2019;156(8):2230–2241.
  • Wai C, Tan BH, Chan CL, et al. Drug-induced liver injury at an Asian center: a prospective study. Liver Int. 2007;27(4):465–474.
  • Suk KT, Kim DJ, Kim CH, et al. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastrenterol. 2012;107(9):1380–1387.
  • Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbal and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399–1408.
  • Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, et al. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16(9):1495–1502.
  • McGill MR, Jaeschke H. Animal models of drug-induced liver injury. Biochim Biophys Acta Mol Basis Dis. 2019;1865(5):1031–1039.
  • Kubes P, Jenne C. Immune responses in the liver. Annu Rev Immunol. 2018;36(1):247–277.
  • Watkins PB. Idiosyncratic liver injury: challenges and approaches. Toxicol Pathol. 2005;33(1):1–5.
  • Dara L, Liu ZX, Kaplowitz N. Mechanisms of adaptation and progression in idiosyncratic drug induced liver injury, clinical implications. Liver Int. 2016;36(2):158–165.
  • Daly AK. Pharmacogenetics and human genetic polymorphisms. Biochem J. 2010;429(3):435–449.
  • Yu K, Geng X, Chen M, et al. High daily dose and being a substrate of cytochrome P450 enzymes are two important predictors of drug-induced liver injury. Drug Metab Dispos. 2014;42(4):744–750.
  • Walgren JL, Mitchell MD, Thompson DC. Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit Rev Toxicol. 2005;35(4):325–361.
  • Pachkoria K, Lucena MI, Ruiz-Cabello F, et al. Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug-induced idiosyncratic liver injury (DILI). Br J Pharmacol. 2007;150(6):808–815.
  • Zhao M, Zhang T, Li G, et al., Associations of CYP2C9 and CYP2A6 polymorphisms with the concentration of valproate and its hepatotoxin metabolites and valproate-induced hepatotoxicity. Basic Clin Pharmacol Toxicol. 2017; 121(2): 138–143.
  • Yimer G, Amogne W, Habtewold A, et al. High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia: a prospective cohort study. Pharmacogenomics J. 2012;12(6):499–506.
  • Huang Y, Chern HD, Su WJ, et al. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology. 2003;37(4):924–930.
  • Hu X, Zhang M, Bai H, et al. Antituberculosis drug-induced adverse events in the liver, kidneys, and blood: clinical profiles and pharmacogenetic predictors. Clin Pharmacol Ther. 2018;104(2):326–334.
  • Heinrich MM, Zembrzuski VM, Ota MM, et al. Factors associated with ant-TB drug-induced hepatotoxicity and genetic polymorphisms in indigenous and non-indigenous populations in Brazil. Tuberculosis (Edinb).. 2016;101::15–24.
  • Sun Q, Liu HP, Zheng RJ, et al. Genetic polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and susceptibility to anti-tuberculosis drug-induced hepatotoxicity: a Chinese population-based prospective case-control study. Clin Drug Investig. 2017;37(12):1125–1136.
  • Zhang J, Zhu X, Li Y, et al. Correlation of CpG island methylation of the cytochrome P450 2E1/2D6 genes with liver injury induced by anti-tuberculosis drugs: a nested case-control study. Int J Environ Res Public Health. 2016;13(8):E776.
  • Daly AK, Aithal GP, Leathart JBS, et al. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology. 2007;132(1):272–281.
  • Acuña G, Foernzler D, Leong D, et al. Pharmacogenetic analysis of adverse drug effect reveals genetic variant for susceptibility to liver toxicity. Pharmacogenomics J. 2002;2(5):327–334.
  • Chen R, Wang J, Tang SW, et al. CYP7A1, BAAT and UGT1A1 polymorphisms and susceptibility to anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2016;20(6):812–818.
  • Wattanapokayakit S, Mushiroda T, Yanai H, et al. NAT2 slow acetylator associated with anti-tuberculosis drug-induced liver injury in Thai patients. Int J Tuberc Lung Dis. 2016;20(10):1364–1369.
  • Sharma SK, Jha BK, Sharma A, et al. Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity. Indian J Med Res. 2016;144(6):924–928.
  • Du H, Chen X, Fang Y, et al. Slow N-acetyltransferase 2 genotype contributes to anti-tuberculosis drug-induced hepatotoxicity: a meta-analysis. Mol Biol Rep. 2013;40(5):3591–3596.
  • Suvichapanich S, Fukunaga K, Zahroh H, et al. NAT2 ultra-slow acetylator and risk of anti-tuberculosis drug-induced liver injury: a genotype-based meta-analysis. Pharmacogenet Genomics. 2018;28(7):167–176.
  • Zhang M, Wang S, Wilffert B, et al. The association between the NAT2 genetic polymorphism and risk of DILI during anti-TB treatment: a systematic review and meta-analysis. Br J Clin Pharmacol. 2018;84(12):2747–2760.
  • Lucena MI, Andrade RJ, Martínez C, et al. Glutathione S-transferase M1 and T1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury. Hepatology. 2008;48(2):588–596.
  • Simon T, Becquemont L, Mary-Krause M, et al. Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther. 2000;67(4):432–437.
  • Watanabe I, Tomita A, Shimizu M, et al. A study to survey susceptible genetic factors responsible for troglitazone-associated hepatotoxicity in Japanese patients with type 2 diabetes mellitus. Clin Pharmacol Ther. 2003;73(5):435–455.
  • Alshabeeb MA, Aithal GP, Daly K. Investigation of oxidative stress-related candidate genes as risk factors for drug-induced liver injury due to co-amoxiclav. DNA Cell Biol. 2020;39(3):349–354.
  • Roy B, Chowdhury A, Kundu S, et al. Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase M1 ‘null’ mutation. J. Gastroenterol Hepatol.. 2001;16(9):1033–1037.
  • Leiro V, Fernández-Villar A, Valverde D, et al. Influence of glutathione S-transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population. Liver Int. 2008;28(6):835–839.
  • Gupta VH, Sing M, Amarapurkar DN, et al. Association of GST null genotypes with anti-tuberculosis drug induced hepatotoxicity in Western Indian population. Ann Hepatol. 2013;12(6):959–965.
  • Monteiro TP, El-Jaick KB, Jeovanio-Silva AL, et al. The roles of GSTM1 and GSTT1 null genotypes and other predictors in anti-tuberculosis drug-induced liver injury. 2012;37(6):712–718.J. Clin Pharm Ther.
  • Chatterjee S, Lyle N, Mandal A, et al. GSTT1 and GSTM1 gene deletions are not associated with hepatotoxicity caused by antitubercular drugs. J Clin Pharm Ther. 2010;35(4):465–470.
  • Bhattacharjee P, Paul S, Banerjee M, et al. Functional compensation of glutathione S-transferase M1 (GSTM1) null by another GST superfamily member, GSTM2. Sci Rep. 2013;3:2704.
  • Lucena MI, García-Martín E, Andrade RJ, et al. Mitochondrial superoxide dismutase and glutathione peroxidase in idiosyncratic drug-induced liver injury. Hepatology. 2010;52(1):303–312.
  • Richie MD, Haas DW, Motsinger AA, et al. Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity. Clin Infect Dis. 2006;43(6):779–782.
  • Haas DW, Bartlett JA, Andersen JW, et al. Pharmacogenetics of nevirapine-associated hepatotoxicity: an adult AIDS clinical trials group collaboration. Clin Infect Dis. 2006;43(6):783–786.
  • Ciccacci C, Borgiani P, Ceffa S, et al. Nevirapine-induced hepatotoxicity and pharmacogenetics: a retrospective study in a population from Mozambique. Pharmacogenomics. 2010;11(1):23–31.
  • Fung KL, Gottesman MM. A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim Biophys Acta. 2009;1794(5):860–871.
  • Fukunaga K, Nakagawa H, Ishikawa T, et al. ABCB1 polymorphism is associated with atorvastatin-induced liver injury in Japanese population. BMC Genet. 2016;17(1):79.
  • Ulzurrun E, Stephens C, Ruiz-Cabello F, et al. Selected ABCB1, ABCB4 and ABCC2 polymorphisms do not enhance the risk of drug-induced hepatotoxicity in a Spanish cohort. PLoS One. 2014;9(4):e94675.
  • Wolking S, Schaeffeler E, Lerche H, et al. Impact of genetic polymorphisms of ABCB1 (MDR1, P-glycoprotein) on drug disposition and potential clinical implications: update of the literature. Clin Pharmacokinet. 2015;54(7):709–735.
  • Choi JH, Ahn BM, Yi J, et al. MRP2 haplotypes confer differential susceptibility to toxic liver injury. Pharmacogenet Genomics. 2007;17(6):403–415.
  • Kim S-H, Kim S-H, Lee J-H, et al. Polymorphisms in drug transporter genes (ABCB1, SLCO1B1 and ABCC2) and hepatitis induced by antituberculosis drugs. Tuberculosis (Edinb).. 2012;92(1):100–104.
  • Urban TJ, Shen Y, Stolz A, et al. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. Pharmacogenet Genomics. 2012;22(11):784–795.
  • Hirano M, Maeda K, Hayashi H, et al. Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther. 2005;314(2):876–882.
  • Henkel SA, Squires JH, Ayers M, et al. Expanding etiology of progressive familial intrahepatic cholestasis. World J Hepatol. 2019;11(5):450–463.
  • Lang C, Meier Y, Stieger B, et al. Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogenet Genomics. 2007;17(1):47–60.
  • Ulzurrun E, Stephens C, Crespo E, et al. Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug-induced liver injury. Liver Int. 2013;33(9):1378–1385.
  • Kagawa T, Hirose S, Arase Y, et al. No contribution of the ABCB11 p.444A polymorphism in Japanese patients with drug-induced cholestasis. Drug Metab Dispos. 2015;43(5):691–697.
  • Chen R, Wang J, Tang S, et al. Role of polymorphic bile salt export pump (BSEP, ABCB11) transporters in anti-tuberculosis drug-induced liver injury in a Chinese cohort. Sci Rep. 2016;6(1):27750.
  • Dröge C, Bonus M, Baumann U, et al. Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants. J Hepatol. 2017;67(6):1253–1264.
  • Hautekeete ML, Horsmans Y, Van Waeyenberge C, et al., HLA association of amoxicillin-clavulanate-induced hepatitis. Gastroenterology. 1999; 117(5): 1181–1186.
  • O’Donohue J, Oien KA, Donaldson P, et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut. 2000;47(5):717–720.
  • Donaldson PT, Daly AK, Henderson J, et al. Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury. J Hepatol. 2010;53(6):1049–1053.
  • Stephens C, López-Nevot MÁ, Ruiz-Cabello F, et al. HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PLoS One. 2013;8(7):e68111.
  • Andrade RJ, Lucena MI, Alonso A, et al. HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease. Hepatology. 2004;39(6):1603–1612.
  • Sharma SK, Balamurugan A, Saha PK, et al. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002;166(7):916–919.
  • Petros Z, Kishikawa J, Makonnen E, et al. HLA-B*57 allele is associated with concomitant anti-tuberculosis and antiretroviral drugs induced liver toxicity in Ethiopians. Front Pharmacol. 2017;8:90.
  • Ocete-Hita E, Salmerón-Fernández M, Urrutia-Maldonado E, et al. Analysis of immunogenetic factors in idiosyncratic drug-induced liver injury in the pediatric population. J Pediatr Gastroenterol Nutr. 2017;64(5):742–747.
  • Li C, Rao T, Chen X, et al. HLA-B*35:01 allele is a potential biomarker for predicting Polygonum multiflorum-induced liver injury in humans. Hepatology. 2019;70(1):346–357.
  • Yang WN, Pang LL, Zhou JY, et al. Single-nucleotide polymorphisms of HLA and Polygonum multiflorum-induced liver injury in the Han Chinese population. World J Gastroenterol. 2020;26(12):1329–1339.
  • Li YJ, Phillips E, Dellinger A, et al. HLA-B*14:01 and HLA-B*35:01 are associated with trimethoprim-sulfamethoxazole induced liver injury. Hepatology. 2020. in press. DOI: 10.1002/hep.31258).
  • Nicoletti P, Aithal GP, Bjornsson ES, et al. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology. 2017;152(5):1078–1089.
  • Hirata K, Takagi H, Yamamoto M, et al. Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J. 2008;8(1):29–33.
  • Lucena MI, Molokhia M, Shen Y, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011;141(1):338–347.
  • Nicoletti P, Barrett S, McEvoy L, et al. Shared genetic risk factors across carbamazepine-induced hypersensitivity reactions. Clin Pharmacol Ther. 2019;106(5):1028–1036.
  • Urban TJ, Nicoletti P, Chalasani N, et al. Minocycline hepatotoxicity: clinical characterization and identification of HLA-B*35:02 as a risk factor. J Hepatol. 2017;67(1):137–144.
  • Bruno CD, Fremd B, Church RJ, et al. HLA associations with infliximab-induced liver injury. Pharmacogenomics J. 2020;20(5):681–686. in press.
  • Daly AK, Donaldson PT, Bhatnagar P, et al., HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009; 41(7): 816–819.
  • Nicoletti P, Aithal GP, Chamberlain TC, et al. Drug-induced liver injury due to flucloxacillin: relevance of multiple human leukocyte antigen alleles. Clin Pharmacol Ther. 2019;106(1):245–253.
  • Illing PT, Vivian JP, Dudek NL, et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. 2012;486(7404):554–558.
  • Monshi MM, Faulkner L, Gibson A, et al. Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T cells provides the immunological basis for flucloxacillin-induced liver injury. Hepatology. 2013;57(2):727–739.
  • Xu CF, Johnson T, Wang X, et al. HLA-B*57:01 confers susceptibility to pazopanib-associated liver injury in patients with cancer. Clin Cancer Res. 2016;22(6):1371–1377.
  • Singer JB, Lewitzky S, Leroy E, et al. A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet. 2010;42(8):711–714.
  • Kindmark A, Jawaid A, Harbron CG, et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J. 2008;8(3):186–195.
  • Spraggs CF, Budde LR, Briley LP, et al. HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. J Clin Oncol. 2011;29(6):667–673.
  • Parham LR, Briley LP, Li L, et al. Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01. Pharmacogenetics J. 2016;16(2):180–185.
  • Nicoletti P, Werk AN, Sawle A, et al. HLA-DRB1*16:01-DQB1*05:02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenet Genomics. 2016;26(5):218–224.
  • Nicoletti P, Devarbhavi H, Goel A, et al. Genome-wide association study (GWAS) to identify genetic risk factors that increase susceptibility to anti-tuberculosis drug-induced liver injury (ATDILI). Hepatology. 2017;66(S1):25A.
  • Cirulli ET, Nicoletti P, Abramson K, et al. A missense variant in PTPN22 is a risk factor for drug-induced liver injury. Gastroenterology. 2019;156(6):1707–1716.
  • Brownlie RJ, Zamoyska R, Salmond RJ. Regulation of autoimmune and anti-tumour T-cell responses by PTPN22. Immunology. 2018;154(3):377–382.
  • Spalinger MR, Schmidt TS, Schwarzfischer M, et al. Protein tyrosine phosphatase non-receptor type 22 modulates colitis in a microbiota-dependent manner. J Clin Invest. 2019;129(6):2527–2541.
  • Suvichapanich S, Wattanapokayakit S, Mushiroda T, et al. Genomewide association study confirming the association of NAT2 with susceptibility to antituberculosis drug-induced liver injury in Thai patients. Antimicrob Agents Chemother. 2019;63(8):e02692–18.
  • Petros Z, Lee MM, Takahashi A, et al. Genome-wide association and replication study of anti-tuberculosis drugs-induced liver toxicity. BMC Genomics. 2016;17(1):755.
  • Pan H, Yang M, Lu L, et al. Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population. Pharmacogenet Genomics. 2019;29(4):84–90.
  • Petros Z, Lee MT, Takahashi A, et al. Genome-wide association and replication study of hepatotoxicity induced by antiretrovirals alone or with concomitant anti-tuberculosis drugs. OMICS. 2017;21(4):207–216.
  • Cao S, Wang C, Ma H, et al. Genome-wide association study on platinum-induced hepatotoxicity in non-small cell lung cancer patients. Sci Rep. 2015;5:(1):11556.
  • Kowalec K, Wright GEB, Drögemöller BI, et al. Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis. Nat Genet. 2018;50(8):1081–1085.
  • Liu Y, Fernandez CA, Smith C, et al. Genome-wide study links PNPLA3 variant with elevated hepatic transaminase after acute lymphoblastic leukemia therapy. Clin Pharmacol Ther. 2017;102(1):131–140.
  • Speliotes EK, Yerges-Armstrong LM, Wu J, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7(3):e1001324.
  • Chambers JC, Zhang W, Sehmi J, et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet. 2011;43(11):1131–1138.
  • Bonkovsky HL, Severson T, Nicoletti P, et al., Genetic polymorphisms implicated in nonalcoholic liver disease or selected other disorders have no influence on drug-induced liver injury. Hepatol Commun. 2019; 3(8): 1032–1035.
  • Wang F-J, Wang Y, Niu T, et al. Update meta-analysis of the CYP2E1 RsaI/PstI and DraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies. J Clin Pharma Ther.. 2016;41(3):334–340.
  • Lazarska KE, Dekker SJ, Vermeulen NP, et al. Effect of UGT2B7*2 and CYP2C8*4 polymorphisms on diclofenac metabolism. Toxicol Lett. 2018;284:70–78.
  • Wuillemin N, Adam J, Fontana S, et al. HLA haplotype determines hapten or p-i T cell reactivity to flucloxacillin. J Immunol. 2013;190(10):4956–4964.
  • Yaseen FS, Saide K, Kim SH, et al., Promiscuous T-cell response to drugs and drug-haptens. J Allergy Clin Immunol. 2015; 136(2): 474–476.
  • Kim SH, Saide K, Farrell J, et al. Characterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induced liver injury. Hepatology. 2015;62(3):887–899.
  • Tailor A, Meng X, Adair K, et al. HLA DRB1*15:01-DQB1*06:02-restricted human CD4+ T-cells are selectively activated with amoxicillin-peptide adducts. Toxicol Sci. 2020;178(1):115–126. in press.
  • Usui T, Tailor A, Faulkner L, et al. HLA-A*33:03-restricted activation of ticlopidine-specific T-cells from human donors. Chem Res Toxicol. 2018;31(10):1022–1024.
  • Yun J, Marcaida MJ, Eriksson KK, et al. Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01. J Immunol. 2014;192(7):2984–2993.
  • Thomson PJ, Illing PT, Farrell J, et al. Modification of the cyclopropyl moiety of abacavir provides insight into the structure activity relationship between HLA-B*57:01 binding and T-cell activation. Allergy. 2020;75(3):636–647.
  • Alfirevic A, Pirmohamed M. Predictive genetic testing for drug-induced liver injury: considerations of clinical utility. Clin Pharmacol Ther. 2012;92(3):376–380.
  • Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–579.
  • U.S. Food & Drug Administration. Drug safety and availability. Medication guides: Ziagen. Available from:https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf#page=27 (accessed 2020 April 23)
  • European Medicines Agency. Medicines. Human. Ziagen. Available from:https://www.ema.europa.eu/en/documents/overview/ziagen-epar-summary-public_en.pdf (accessed 2020 April 23)
  • Kaliyaperumal K, Grove JI, Delahay RM, et al., Pharmacogenomics of drug-induced liver injury (DILI): molecular biology to clinical applications. J Hepatol. 2018; 69(4): 948–957.
  • European Association for the Study of the Liver. EASL clinical practice guidelines: autoimmune hepatitis. J Hepatol. 2015;63(4):971–1004.
  • Czaja AJ, Kruger M, Santrach PJ, et al. Genetic distinction between types 1 and 2 autoimmune hepatitis. Am J Gastroenterol. 1997;92(12):2197–2200.
  • Stephens C, Castiella A, Gomez-Moreno EM, et al. Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles. Pharmacogenet Genomics. 2016;26(9):414–422.
  • de Boer YS, van Gerven NM, Zwiers A, et al. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1. Gastroenterology. 2014;147(2):443–452.
  • Umemura T, Katsuyama Y, Yoshizawa K, et al. Human leukocyte antigen class II haplotypes affect clinical characteristics and progression of type 1 autoimmune hepatitis in Japan. PLoS One. 2014;9(6):e100565.
  • Lim YS, Oh HB, Choi SE, et al. Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLA-DRB1 molecule. J Hepatol. 2008;48(1):133–139.
  • Tam V, Patel N, Turcotte M, et al. Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019;20(8):467–484.
  • Czaja AJ. Epigenetic changes and their implications in autoimmune hepatitis. Eur J Clin Invest. 2018;48(4):e12899.
  • Koido M, Kawakami E, Fukumura J, et al. Polygenic architecture informs potential vulnerability to drug-induced liver injury. Nat Med. 2020;26(10):1541–1548.
  • Adolph TE, Grander C, Moschen AR, et al. Liver-microbiome axis in health and disease. Trends Immunol. 2018;39(9):712–723.
  • Ali OH, Berner F, Bomze D, et al. Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors. Eur J Cancer. 2019;107:8–14.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.