Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM


  • Rolf Teschke Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, D-63450 Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/ Main, Frankfurt/Main, Germany



Immunity, Autoimmunity, Hepatic immune cells, Idiosyncratic drug induced liver injury, RUCAM, Cytochrome P450, HLA B*57:01, Immune-mediated hypothesis


Idiosyncratic drug induced liver injury (iDILI) is a multifaceted and fairly well described liver disease, but there is yet some uncertainty on the role of immune systems triggering the liver injury and speculation on the cascade of immune events. Many conclusions were so far based on narratives or cases of iDILI, which did not receive the benefit of a robust causality assessment like by the Roussel Uclaf Causality Assessment Method (RUCAM). This analysis aims to clarify the cascade of immune events that lead to the liver injury by conventional drugs. For this approach, the search focused on iDILI cases with verified diagnosis by RUCAM. Most promising were parameters obtained from the blood as mirror of what happened in the liver during the injurious processes.The focus of this present analysis is on patients with RUCAM based iDILI and concomitant immune-related parameters in the blood. As an example, compelling evidence for a role of immune systems in iDILI was found for circulating mediators in the blood secreted by liver immune cells in patients under a therapy for tuberculosis, detected were also serum anti-cytochrome P450 (CYP) antibodies in patients after anesthesia with sevoflurane or desflurane and thereby reflecting their metabolism by the CYP 2E1 isoform, the occurrence of serum of autoantibodies in patients with drug induced autoimmune hepatitis (DIAIH) due to many drugs, and the role of blood and liver monocytes, which provide direct evidence for the activation of the hepatic innate immune system to the adapted immune system. In essence, patients with RUCAM based iDILI show various immunology features in the blood compatible with the role of the hepatic immune systems in patients with suspected iDILI caused by some but not all drugs.


Kobayashi T, Iwaki M, Nogami A, Yoneda M. Epidemiology and management of drug-induced liver injury: importance of the updated RUCAM. J Clin Transl Hepatol 2023; 11: 1239-1245.

Hosack T, Damry D, Biswas S. Drug-induced liver injury: a comprehensive review. Therap Adv Gastroenterol 2023; 16: 17562848231163410.

Allison R, Guraka A, Shawa IT,Tripathi G, Moritz W, Kermanizadet A. Drug induced liver injury - a 2023 update. J Toxicol Environ Health. Part B, Critical Reviews 2023: 1-26.

Ke L, Lu C, Shen R, Lu T, Ma B, Hua Y. Knowledge mapping of drug-induced liver injury: A scientometric investigation (2010-2019). Front Pharmacol 2020; 11: 842.

Danan G, Bénichou C. Causality assessment of adverse reactions to drugs—I. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries. J Clin Epidemiol 1993; 46: 1323-1330.

Bénichou C, Danan G, Flahault A. Causality assessment of adverse reactions of drugs - II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol 1993; 46: 1331-1336.

Danan G, Teschke R. RUCAM in drug and herb induced liver injury: The update. In Special Issue: Drug, Herb, and Dietary Supplement Hepatotoxicity, guest editors Rolf Teschke, Raúl J. Andrade. Int J Mol Sci 2016; 17: 14.

Díaz-Orozco L, Quiroz-Compean F, Aquino-Matus J, Teschke R, Méndez-Sánchez N. Severe DILI in a patient under polypharmacy including rosuvastatin: diagnostic challenges and lessons from a case report assessed using the updated RUCAM algorithm. Int J Gastroenterol Hepatol Dis 2022; 1: e250422203997.

Studentova H, Volakova J, Spisarova M, Zemankova A, Aiglova K, Szotkowski T, Melichar B. Severe tyrosine-kinase inhibitor induced liver injury in metastatic renal cell carcinoma patients: two case reports assessed for causality using the updated RUCAM and review of the literature. BMC Gastroenterol 2022; 22: 49.

Wurzburger R. A case of delayed hepatic injury associated with teriflunomide use as assessed for causality using the updated RUCAM. Case Reports Hepatol 2022; Article ID 6331923.

Shi X, Lao D, Xu Q, Li X, Lv Q. A case report of drug-induced liver injury after tigecycline administration: histopathological evidence and a probable causality grading as assessed by the updated RUCAM diagnostic scale. BMC Infect Dis 2022; 22: 368.

Plüß M, Tampe D, Schwörer H, Bremer SCB, Tampe B. Case report: Kinetics of humanleukocyte antigen receptor HLA-DR during liver injury induced by potassium para aminobenzoate as assessed for causality using the updated RUCAM. Front Pharmacol 2022; 13: 966910.

Abeles RD, Foxton M, Khan S, Goldin R, Smith B, Thursz MR, Verma S. Androgenicanabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature. BMJ Open Gastroenterol 2020; 7: e000549.

Tzadok R, Levy S, Aouizerate J, Shibolet O. Acute liver failure following a single dose of atezolizumab, as assessed for causality using the updated RUCAM. Case Rep Gastrointest Med 2022; 2022: 5090200.

Swanson LA, Kassab I, Tsung I, Schneider BJ, Fontana RJ. Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Front Oncol 2022; 12: 984940.

Shumar J, Ordway S, Junga Z, Sadowski B, Torres D. Memantine-induced liver injury with probable causality as assessed using the Roussel Uclaf Causality Assessment Method (RUCAM). ACG Case Rep J 2019; 6: e00184.

Danjuma MI, Almasri H, Alshokri S, Khir FK, Elmalik A, Battikh NG, Abdallah IMH, Elshafei M, Fatima H, Mohamed MFH, Maghoub Y, Hussain T, Kamal I, Anwer Z, Bidmos MA, Elzouki AN. Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. BMC Geriatr 2020; 20: 346.

Ye L, Feng Z, Huang L, Guo C, Wu X, He L, Tan W, Wang Y, Wu X, Hu B, Li T, Yang G, Chengxian G,He Q. Causality evaluation of drug-induced liver injury in newborns and children in the intensive care unit using the updated Roussel Uclaf Causality Assessment Method. Front Pharmacol 2021; 12: 790108.

Lunardelli MM, Becker MW, Ortiz GX, Blatt CR. Drug-induced liver injury causality assessment data from a crosssectional study In Brazil: A call for the use of updated RUCAM in hospital pharmacy. Rev Bras Farm Hosp Serv Saude2022; 13: 791-800.

Protzer U, Maini MK, Knolle PA. Living in the liver: hepatic infections. Nat Rev Immunol 2012; 12: 201-213. doi: 10.1038/nri3169.

Guillot A, Tacke F. Liver macrophages: Old dogmas and new insights. Hepatol Commun 2019; 3: 730-743.

Roohani S, Tacke F. Liver Injury and the macrophage issue: molecular and mechanistic facts and their clinical relevance. Int J Mol Sci 2021; 22: 7249.

Ahmed O, Robinson MW, O’Farrelly C. Inflammatory processes in the liver: divergent roles in homeostasis and pathology. Cell Mol Immunol 2021; 18: 1375-1386.

Colino CI, Lanao JM, Gutierrez-Millan C. Targeting of hepatic macrophages by therapeutic nanoparticles. Front Immunol 2020; 11: 218.

Sellau J, Puengel T, Hoenow S, Groneberg M, Tacke F, Lotter H. Monocyte dysregulation: consequences for hepatic infections. Semin Immunopathol 2021; 43: 493-506.

Robinson M, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol 2016; 13: 267-276.

Sellau J, Puengel T, Hoenow S, Groneberg M, Tacke F, Lotter H. Monocyte dysregulation: consequences for hepatic infections. Semin Immunopathol 2021; 43: 493-506.

Kamm DR, McCommis KS. Hepatic stellate cells in physiology and pathology. J Physiol 2022; 600: 1825-1837.

Kordes C, Bock HH, Reichert D, May P, Häussinger D. Hepatic stellate cells: current state and open questions. Biol Chem 2021; 402: 1021-1032.

Méndez-Sánchez N, Córdova-Gallardo J, Barranco-Fragoso B, Eslam M. Hepatic dendritic cells in the development and progression of metabolic steatohepatitis. Front Immunol 2021; 12: 641240.

Fan X, Men R, Huang C, Shen M, Wang T, Ghnewa Y, Ma Y, Ye T, Yang L. Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation. Cell Death Dis 2020; 11: 23.

Taylor SA, Assis DN, Mack CL. The contribution of B cells in autoimmune liver diseases. Semin Liver Dis 2019; 39: 422-431.

Lopez-Scarim J, Nambiar SM, Billerbeck E. Studying T Cell responses to hepatotropic viruses in the liver microenvironment. Vaccines (Basel) 2023; 11: 681.

Sturm N, Thélu MA, Camous X, Dimitrov G, Ramzan M, Dufeu-Duchesne T, Bonorino P, Guillermet C, Brambilla E, Arvers P, Pernollet M, Leroy V, Zarski JP, Marche PN, Jouvin-Marche E. Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis. J Hepatol 2010; 53: 25-35.

Shetty S, Lalor PF, Adams DH. Liver sinusoidal endothelial cells - gatekeepers of hepatic immunity. Nat Rev Gastroenterol Hepatol 2018; 15: 555-567.

Ibrahim SH. Sinusoidal endotheliopathy in nonalcoholic steatohepatitis: therapeutic implications. Am J Physiol Gastrointest Liver Physiol 2021; 321: G67-G74.

Teschke R, Danan G. Review: Drug induced liver injury with analysis of alternative causes as confounding variables. Br J Clin Pharmacol 2018; 84: 1467-1477.

Huang YS, Tseng SY, Chen WW, Chang TT, Peng CY, Lo GH, Hsu CW, Hu CT, Huang YH. Clinical characteristics and outcomes of drug-induced liver injury in Taiwan: with emphasis on the impact of chronic hepatitis B infection. J Chin Med Assoc 2022; 85: 286-294.

Teschke R, Danan G. The LiverTox paradox - gaps between promised data and reality check. Diagnostics (Basel) 2021; 11: 1754.

Björnsson ES. Hepatotoxicity by drugs: the most common implicated agents.In Special Issue: Drug, Herb, and Dietary Supplement Hepatotoxicity, guest editors Rolf Teschke, Raúl J.Andrade.Int J Mol Sci 2016; 17: 224.

Björnsson ES, Hoofnagle JH. Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports. Hepatology 2016; 63: 590-603.

Teschke R, Danan G. Worldwide use of RUCAM for causality assessment in 81,856 DILI and 14,029 HILI cases published 1993-mid 2020: A comprehensive analysis. Medicines 2020; 7: 62.

Ho CM, Chen CL, Chang CH, Lee MR, Wang JY, Hu RH, Lee PH. Circulatory inflammatory mediators in the prediction of anti-tuberculous drug-induced liver injury using RUCAM for causality assessment. Biomedicines 2021; 9: 891.

Teschke R, Danan G. Advances in idiosyncratic drug induced liver injury issues: new clinical and mechanistic analysis due to Roussel Uclaf Causality Assessment Method use. In Special Issue: Molecular Toxicology of Drug Induced Liver injury,section of Molecular Toxicology. Int J Mol Sci 2023; 24: 10855.

Nicoll A, Moore D, Njoku D, Hockey B. Repeated exposure to modern volatile aesthetics may cause chronic hepatitis as well as acute liver injury. BMJ Case Rep 2012; 2012: bcr2012006543.

Bishop B, Hannah N, Doyle A, Amico F, Hockey B, Moore D, Sood S, Gorelik A, Liew D, Njoku D, Nicoll A. A prospective study of the incidence of drug-induced liver injury by the modern volatile anaesthetics sevoflurane and desflurane. Aliment Pharmacol Ther 2019; 49: 940-951.

Teschke, R, Uetrecht J. Mechanism of idiosyncratic drug induced liver injury (DILI): Unresolved basic issues. In special issue: Unresolved basic issues in hepatology, guest editors Ralf Weiskirchen, Wolfgang Stremmel. Ann Transl Med 2021; 9: 730.

Teschke, R.; Danan, G. Idiosyncratic drug induced liver injury, cytochrome P450, metabolic risk factors and lipophilicity: Highlights and controversies. Int J Mol Sci 2021; 22: 3441.

Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005; 42: 481-489.

Naseralallah LM, Aboujabal BA, Geryo NM, Al Boinin A, Al Hattab F, Akbar R, Umer W, Abdul Jabbar L, Danjuma MI. The determination of causality of drug induced liver injury in patients with COVID-19 clinical syndrome. PLoS One 2022; 17: e0268705.

Meunier L, Larrey D.Drug-induced liver injury: Biomarkers, requirements, candidates, and validation. Special issue: Clinical drug induced liver injury: Current diagnostic and mechanistic challenges, guest editors: Rolf Teschke, Gaby Danan, James H. LewisFront Pharmacol2019; 10: 1482.

Sutti S, Rigamonti C, Vidali M, Albano E. CYP2E1 autoantibodies in liver diseases. Redox Biol 2014; 3: 72-78.

Jee A, Sernoskie SC, Uetrecht J. Idiosyncratic drug-induced liver injury: Mechanistic and clinical challenges. Int J Mol Sci 2021; 22: 2954.

Njoku DB, Mellerson JL, Talor MV, Kerr DR, Faraday NR, Outshoor I, Rose NR. Role of CYP2E1 immunoglobulin G4 subclass antibodies and complement in the pathogenesis of idiosyncratic drug-induced hepatitis, Clin Vaccine Immunol 2006; 13: 258-265.

Bourdi M, Chen W, Peter RM, Martin JL, Buters JT, Nelson SD, Pohl LR. Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem Res Toxicol 1996; 9: 1159-1166.

Kenna JG, Neuberger J, Williams R. Identification by immunoblotting of 3 halothane-induced liver microsomal polypeptide antigens recognized by antibodies in sera from patients with halothane-associated hepatitis. J Pharmacol Exp Ther 1987; 242: 733-740.

Njoku DB, Greenberg RS, Bourdi M, Borkowf CB, Dake EM, Martin JL,Pohl LR. Autoantibodies associated with volatile anesthetic hepatitis found inthe sera of a large cohort of pediatric anesthesiologists. Anesth Analgesia 2002; 94: 243-249.

Uetrecht J. Idiosyncratic drug reactions: past, present, and future. Chem Res Toxicol 2008; 21: 84-92.

Larrey D. Epidemiology and individual susceptibility to adverse drug reactions affecting the liver. Semin Liver Dis 2002; 22: 145-155.

Reike-Kunze M, Zenouzi R, Hartel J, Krech T, Weidemann S, Sterneck M, Weiler-Normann C, Lohse AW, Schramm C, Sebode M. Drug-induced liver injury at a tertiary care centre in Germany: Model for end-stage liver disease is the best predictor of outcome. Liver Int 2021; 41: 2383-2395. doi: 10.1111/liv.14985.

Yang J, Yu YL, Jin Y, Zhang Y, Zheng CQ. Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis. World J Gastroenterol 2016; 22: 7579-7586.

Uetrecht J. Mechanistic studies of idiosyncratic DILI: Clinical implications. In: Special issue: Clinical drug induced liver injury: Current diagnostic and mechanistic challenges, guest editors: Rolf Teschke, Gaby Danan, James H. Lewis. Front Pharmacol 2019; 10: 837.

Benesic A, Leitl A, Gerbes AL. Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury. Gut 2016; 65: 1555-1563.

Teschke R. Treatment of drug-induced liver injury. In Special Issue: Liver Disease and Therapy, Guest Editor: Nahum Méndez-Sánchez. Biomedicines 2023; 11: 15.

Dragoi D, Benesic A, Pichler G, Kulak NA, Bartsch HS, Gerbes AL. Proteomics analysis of monocyte-derived hepatocyte-like cells identifies Integrin Beta 3 as a specific biomarker for drug-induced liver injury by diclofenac. Front Pharmacol 2018; 9: 699.

Espinoza VE, Emmady PD. Histology, Monocytes. (Updated 2022 April 28). In: StatPearls (Internet), Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

Tan CK, Ho D, Wang LM, Kumar R. Drug-induced autoimmune hepatitis: A minireview. World J Gastroenterol 2022; 28: 2654-2666.

Licata A, Maida M, Cabibi D, Butera G, Macaluso FS, AlessiN, Caruso C, Craxì A, Almasio PL. Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: A retrospective cohort study. Dig Liver Dis 2014; 46: 1116-1120.

Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M. Ortega-Alonso A, Sanabria-Cabrera J, Gonzalez-Jimenez A, Alvarez-Alvarez I, Slim M, Jimenez-PerezM; et al. Participating clinical centres. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol 202: 75: 86-97.

de Boer YS, Kosinski AS, Urban TJ, Zhao Z, Long N, Chalasani N, Kleiner DE, Hoofnagle JH.; Drug-Induced Liver Injury Network. Features of autoimmune hepatitis in patients with drug-induced liver injury. Clin Gastroenterol Hepatol 2017; 15: 103-112.e2.

Weber S, Benesic A, Rotter I, Gerbes AL. Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug induced-liver injury from autoimmune hepatitis. Liver Int 2019; 39: 1906-1917.

Valgeirsson KB, Hreinsson JP, Björnsson ES. Increased incidence of autoimmune hepatitis is associated with wider use of biological drugs. Liver Int 2019; 39: 2341-2349.

Shelton E, Chaudrey K, Sauk J, Khalili H, Masia R, Nguyen DD, Yajnik V, Ananthakrishnan AN. New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2015; 41: 972-979.

Martínez-CasasOY, Díaz-Ramírez GS, Marín-Zuluaga JI, Muñoz-Maya O, Santos O, Donado-Gómez J.H, RestrepoGutiérrez JC. Differential characteristics in drug-induced autoimmune hepatitis. JGH Open 2018; 2: 97-104.

Yeong TT, Lim KHJ, Goubet S, Parnell N, Verma S. Natural history and outcomes in drug-induced autoimmune hepatitis. Hepatol Res 2016; 46: E79-E88.

Hisamochi A, Kage M, Ide T, Arinaga-Hino T, Amano K, Kuwahara R, Ogata K, Miyajima I, Kumashiro R, Sata M,Torimura T. An analysis of drug-induced liver injury, which showed histological findings similar to autoimmune hepatitis. J Gastroenterol 2016; 51: 597-607.

Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL, Bittencourt PL, Porta G, Boberg KM, Hofer H, Bianchi FB, Shibata M, Schra mm C, Eisenmann de Torres B, Galle PR, McFarlane I, Dienes HP, Lohse AW, and International Autoimmune Hepatitis Group. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008; 48: 169-176.

Sakulsaengprapha V, Wasuwanich P, Naraparaju G, Korotkaya Y, Thawillarp S, Oshima K, Karwowski C, Scheimann AO, Karnsakul W. Applicability of International Autoimmune Hepatitis Group (IAIGH) scoring system for autoimmune hepatitis in pediatrics. Biology 2023; 12: 479.

Devarbhavi H, Raj S, Aradya VH, Rangegowda VT, Veeranna GP, Singh R, Reddy V, Patil M. Drug-induced liver injury associated with Stevens-Johnson syndrome/toxic epidermal necrolysis: Patient characteristics, causes, and outcome in 36 cases. Hepatology 2016; 63: 993.

Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A review of diagnosis and management. Medicina 2021; 57: 895.

Su SC, Mockenhaupt M, Wolkenstein P, Dunant A, Le Gouvello S, Chen CB, Chosidow O, Valeyrie-Allanore L, Bellon T, Sekula P, Wang CW, Schumacher M, Kardaun SH, Hung SI, Roujeau JC, Chung WH. Interleukin-15 Is associated with severity and mortality in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. J Invest Dermatol 2017; 137: 1065-1073.

Nicoletti P, Aithal GP, Chamberlain TC, Coulthard S, Alshabeeb M, Grove JI, Andrade RJ, Bjornsson E, Dillon JF, Hallberg P, Lucena MI, Maitland-van der Zee AH, Martin JH, Molokhia M, Pirmohamed M, Wadelius M, Shen Y, Nelson MR, Daly AK; International Drug-Induced Liver Injury Consortium (iDILIC). Drug-induced liver injury due to Flucloxacillin: Relevance of multiple Human Leukocyte Antigen alleles. Clin Pharmacol Ther 2019; 106: 245-253.

Stephens C, López-Nevot MÁ, Ruiz-Cabello F, Ulzurrun E, Soriano G, Romero-Gómez M, Romero-Casares A, Lucena MI, Andrade RJ. HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PloS one 2013; 8: e68111.

O’Donohue J, Oien KA, Donaldson P, Underhill J, Clare M, MacSween RN, Mills PR. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut 2000; 47: 717-720.

Devarbhavi H, Patil M, Menon M. Association of human leukocyte antigen-B*13: 01 with dapsone-induced liver injury. Brit J Clin Pharmacol 2022; 88: 1369-1372.

Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, Barnhart HX, Bondon-Guitton E, Hayashi PH, Bessone F, Carvajal A, Cascorbi I, Cirulli ET, Chalasani N, Conforti A, Coulthard SA, Daly MJ, Day CP, Dillon JF, Fontana RJ, Grove JI, Hallberg P, Hernández N, Ibáñez L, Kullak-Ublick GA, Laitinen T, Larrey D, Lucena MI, Maitland-van der Zee AH, Martin JH, Molokhia M, Pirmohamed M, Powell EE, Qin S, Serrano J, Stephens C, Stolz A, Wadelius M, Watkins PB, Floratos A, Shen Y, Nelson MR, Urban TJ, Daly AK; International Drug-Induced Liver Injury Consortium, Drug-Induced Liver Injury Network Investigators, and International Serious Adverse Events Consortium. 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: 1078-1089.

Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, Daly MJ, Goldstein DB, John S, Nelson MR, Graham J, Park BK, Dillon JF, Bernal W, Cordell HJ, Pirmohamed M, Aithal GP, Day CP; DILIGEN Study; International SAE Consortium. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009; 41: 816-819.

Monshi MM, Faulkner L, Gibson A, Jenkins RE, Farrell J, Earnshaw CJ, Alfirevic A, Cederbrant K, Daly AK, French N, Pirmohamed M, Park BK, Naisbitt DJ. 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: 727-739.

Teixeira M, Macedo S, Batista T, Martins S, Correia A, Matos LC. Flucloxacillin-induced hepatotoxicity: association with HLA-B*5701. Rev Assoc Med Bras 2020; 66: 12-17.

Nicoletti P, Werk AN, Sawle A, Shen Y, Urban TJ, Coulthard SA, Bjornsson ES, Cascorbi I, Floratos A, Stammschulte T, Gundert-Remy U, Nelson MR, Aithal GP, Daly AK; International Drug-induced Liver Injury Consortium. HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenet Genomics 2016; 26: 218-224.

Bruno CD, Fremd B, Church RJ, Daly AK, Aithal GP, Björnsson ES, Larrey D, Watkins PB, Chow CR. HLA associations with infliximab-induced liver injury. Pharmacogenomics J 2020; 20: 681-686.

Li X, Jin S, Fan Y, Fan X, Tang Z, Cai W, Yang J, Xiang X. Association of HLA-C*03: 02 with methimazole-induced liver injury in Graves' disease patients. Biomed Pharmacother 2019; 117: 109095.

Urban TJ, Nicoletti P, Chalasani N, Serrano J, Stolz A, Daly AK, Aithal GP, Dillon J, Navarro V, Odin J, Barnhart H, Ostrov D, Long N, Cirulli ET, Watkins PB, Fontana RJ; Drug-Induced Liver Injury Network (DILIN); Pharmacogenetics of Drug-Induced Liver Injury group (DILIGEN); International Serious Adverse Events Consortium (iSAEC). Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35: 02 as a risk factor. J Hepatol 2017; 67: 137.

Daly AK, Björnsson ES, Lucena MI, Andrade RJ. Drug-induced liver injury due to nitrofurantoin: Similar clinical features, but different HLA risk alleles in an independent cohort. J Hepatol 2023; 78: e165-e182.

Li YJ, Phillips EJ, Dellinger A, Nicoletti P, Schutte R, Li D, Ostrov DA, Fontana RJ, Watkins PB, Stolz A, Daly AK, Aithal GP, Barnhart H, Chalasani N; Drug-induced Liver Injury Network. Human Leukocyte Antigen B*14: 01 and B*35: 01 are associated with trimethoprim-sulfamethoxazole induced liver injury. Hepatology 2021; 73: 268-281.

Daly AK. Genetics of drug-induced liver injury: Current knowledge and future prospectives. Clin Transl Sci 2023; 16: 37-42.

Teschke R, Danan G. HLA genetics in idiosyncratic drug induced liver injury cases with evidence based on RUCAM. Int J Mol Sci 2023 in press.