Advertisement

Current Hepatology Reports

, Volume 18, Issue 3, pp 274–279 | Cite as

Global Epidemiology of Drug-Induced Liver Injury (DILI)

  • Einar S. BjörnssonEmail author
Drug-Induced Liver Injury (P Hayashi, Section Editor)
  • 26 Downloads
Part of the following topical collections:
  1. Topical Collection on Drug-Induced Liver Injury

Abstract

Purpose of Review

Drug-induced liver injury (DILI) is not an uncommon liver disease in many parts of the world. DILI is one of the most common causes of acute liver failure in most countries. The current review summarizes the global epidemiology of DILI.

Recent Findings

The number need to harm in terms of DILI due to amoxicillin-clavulanate was approximately 1 out 2300, but was higher for azathioprine (1 out of 133) and infliximab (1 out of 148). A retrospective Chinese study showed the highest rate of DILI in hospitalized patients with an incidence of approximately 24 patients per 100,000 annually with a more favorable prognosis in the DILI cohort than previously reported from Europe, the USA, and Asia.

Summary

Although large DILI registries from Europe and the USA have collected much data, more prospective studies with continual enrollment are needed particularly as new therapies such as immune modulatory and oncological medications with longer half-lives and latencies come to market.

Keywords

DILI Hepatotoxicity Epidemiology Incidence Prognosis Global 

Notes

Compliance with Ethical Standards

Conflict of Interest

Einar S. Björnsson declares no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Garcia Rodriguez LA, Ruigomez A, Jick H. A review of epidemiologic research on drug-induced acute liver injury using the general practice research database in the United Kingdom. Pharmacotherapy. 1997;17:721–8.Google Scholar
  2. 2.
    de Abajo FJ, Montero D, Madurga M, Madurga M, García RL. Acute and clinically relevant drug-induced liver injury: a population based case-control study. Br J Clin Pharmacol. 2004;58:71–80.CrossRefGoogle Scholar
  3. 3.
    Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology. 2005;42:481–9.CrossRefGoogle Scholar
  4. 4.
    Björnsson B, Bergqvist A, Jerlstad P, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005;40:1095–101.CrossRefGoogle Scholar
  5. 5.
    de Valle M, Klinteberg V, Alem N, Olsson R, Björnsson E. Drug-induced liver injury in a Swedish University hospital outpatient hepatology clinic. Aliment Pharmacol Ther. 2006;24:1187–95.CrossRefGoogle Scholar
  6. 6.
    Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105:2396–404.CrossRefGoogle Scholar
  7. 7.
    Idilman R, Bektas M, Cinar K, Toruner M, Cerit ET, Doganay B, et al. The characteristics and clinical outcome of drug-induced liver injury: a single-center experience. J Clin Gastroenterol. 2010;44:e128–32.CrossRefGoogle Scholar
  8. 8.
    Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129:512–21.CrossRefGoogle Scholar
  9. 9.
    Wai C-T, Tan B-H, Chan C-L, Sutedja DS, Lee Y-M, Khor C, et al. Drug-induced liver injury at an Asian center: a prospective study. Liver Int. 2007;27:465–74.CrossRefGoogle Scholar
  10. 10.
    Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34.CrossRefGoogle Scholar
  11. 11.
    Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148:1340–52.CrossRefGoogle Scholar
  12. 12.
    Suk KT, Kim DJ, Kim CH, Park SH, Yoon JH, Kim YS, et al. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastroenterol. 2012;107:1380–7.CrossRefGoogle Scholar
  13. 13.
    Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, et al. Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology. 2002;36:451–5.CrossRefGoogle Scholar
  14. 14.
    Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25.CrossRefGoogle Scholar
  15. 15.
    • Vega M, Verma M, Beswick D, Bey S, Hossack J, Merriman N, et al. The incidence of drug- and herbal and dietary supplement-induced liver injury: preliminary findings from gastroenterologist-based surveillance in the population of the state of Delaware. Drug Saf. 2017;40:783–7. An important first population-based study of DILI in the USA. CrossRefGoogle Scholar
  16. 16.
    Wei G, Bergquist A, Broomé U, Lindgren S, Wallerstedt S, Almer S, et al. Acute liver failure in Sweden: etiology and outcome. J Intern Med. 2007;262:393–401.CrossRefGoogle Scholar
  17. 17.
    Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SHB, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947–54.CrossRefGoogle Scholar
  18. 18.
    Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transplant. 2004;10:1018–23.CrossRefGoogle Scholar
  19. 19.
    Reuben A, Koch DG, Lee WM, Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76.CrossRefGoogle Scholar
  20. 20.
    Ohmori S, Shiraki K, Inoue H, Okano H, Yamanaka T, Deguchi M, et al. Clinical characteristics and prognostic indicators of drug-induced fulminant hepatic failure. Hepatogastroenterology. 2003;50:1531–4.Google Scholar
  21. 21.
    Zhao P, Wang C, Liu W, Chen G, Liu X, Wang X, et al. Causes and outcomes of acute liver failure in China. PLoS One. 2014;22(8):e80991.Google Scholar
  22. 22.
    Devarbhavi H, Patil M, Reddy VV, Singh R, Joseph T, Ganga D. Drug-induced acute liver failure in children and adults: results of a single-centre study of 128 patients. Liver Int. 2018;38:1322–9.CrossRefGoogle Scholar
  23. 23.
    Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014 Oct;60(4):1399–408.CrossRefGoogle Scholar
  24. 24.
    Navarro V, Khan I, Björnsson E, Seef LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017;65:363–73.CrossRefGoogle Scholar
  25. 25.
    Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, et al. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16:1495–502.CrossRefGoogle Scholar
  26. 26.
    •• Björnsson ES, Hoofnagle JH. Categorization of drugs implicated in causing liver injury: critical assessment based upon published case reports. Hepatology. 2016;63:590–603. Critical analysis of published case reports of DILI. Only 353 drugs marketed in the USA had convincingly been linked to liver injury. CrossRefGoogle Scholar
  27. 27.
    Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I, Stephens C, García-Cortes M, García-Muñoz B, et al. Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther. 2015 Jan;41(1):116–25.CrossRefGoogle Scholar
  28. 28.
    • Stolz A, Navarro V, Hayashi PH, Fontana RJ, Barnhart HX, Gu J, et al. Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors. Aliment Pharmacol Ther. 2019;49:1195–204. An important observational study shows that ingested products often contained anabolic steroids not identified on the label.CrossRefGoogle Scholar
  29. 29.
    Azad A, Chang P, Devuni D, Bichoupan K, Kesar V, Branch AD, et al. Real world experience of drug induced liver injury in patients undergoing chemotherapy. J Clin Gastroenterol Hepatol. 2018;2:pii: 18.  https://doi.org/10.21767/2575-7733.1000047.CrossRefGoogle Scholar
  30. 30.
    Antonazzo IC, Poluzzi E, Forcesi E, Riise T, Bjornevik K, Baldin E, et al. Liver injury with drugs used for multiple sclerosis: a contemporary analysis of the FDA Adverse Event Reporting System. Mult Scler. 2018 Sep;19:1352458518799598.Google Scholar
  31. 31.
    Björnsson ES, Gunnarsson BI, Gröndal G, Jonasson JG, Einarsdottir R, Ludviksson BR, et al. The risk of drug-induced liver injury from tumor necrosis factor (TNF)-alpha-antagonists. Clin Gastroenterol Hepatol. 2015;13:602–8.CrossRefGoogle Scholar
  32. 32.
    Björnsson E, Bergmann O, Jonasson JG, Grondal G, Gudbjornsson B, Olafsson S. Drug-induced autoimmune hepatitis: response to corticosteroids and lack of relapse after cessation of steroids. Clin Gastroenterol Hepatol. 2017;15:1635–6.CrossRefGoogle Scholar
  33. 33.
    Ricciuto A, Kamath BM, Walters TD, Frost K, Carman N, Church PC, et al. New onset autoimmune hepatitis during anti-tumor necrosis factor-alpha treatment in children. J Pediatr. 2018;194:128–35.CrossRefGoogle Scholar
  34. 34.
    Bishop B, Hannah N, Doyle A, Amico F, Hockey B, Moore D, et al. A prospective study of the incidence of drug- induced liver injury by the modern volatile anaesthetics sevoflurane and desflurane. Aliment Pharmacol Ther. 2019;49:940–51.CrossRefGoogle Scholar
  35. 35.
    Bagheri H, Michel F, Lapeyre-Mestre M, Lagier E, Cambus JP, Valdiguie P, et al. Detection and incidence of drug-induced liver injuries in hospital: a prospective analysis from laboratory signals. Br J Clin Pharmacol. 2000;50:479–84.CrossRefGoogle Scholar
  36. 36.
    Meier Y, Cavallaro M, Roos M, Pauli-Magnus C, Folkers G, Meier PJ, et al. Incidence of drug-induced liver injury in medical inpatients. Eur J Clin Pharmacol. 2005;61:135–43.CrossRefGoogle Scholar
  37. 37.
    Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, et al. Risk of acute liver injury associated with the use of drugs: a multicentre population survey. Aliment Pharmacol Ther. 2007;25:1401–9.CrossRefGoogle Scholar
  38. 38.
    Hussaini SH, O’Brien CS, Despott EJ, Dalton HR. Antibiotic therapy: a major cause of drug-induced liver injury. Eur J Gastroenterolo Hepatol. 2007;19:15–20.CrossRefGoogle Scholar
  39. 39.
    Douros A, Bronder E, Andersohn F, Klimpel A, Thomae M, Sarganas G, et al. Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study. Br J Clin Pharmacol. 2015;79:988–99.CrossRefGoogle Scholar
  40. 40.
    Friedrich ME, Akimova E, Huf W, Konstantinidis A, Papageorgiou K, Winkler D, et al. Drug-induced liver injury during antidepressant treatment: results of AMSP, a Drug Surveillance Program. Int J Neuropsychopharmacol. 2016;19:1–9.CrossRefGoogle Scholar
  41. 41.
    Baekdal M, Ytting H, Skalshøi MK. Drug-induced liver injury: a cohort study on patients referred to the Danish transplant center over a five year period. Scand J Gastroenterol. 2017;52:450–4.CrossRefGoogle Scholar
  42. 42.
    Björnsson E, Nordlinder H, Olsson R. Clinical characteristics and prognostic markers in disulfiram-induced liver injury. J Hepatol. 2006;44:791–7.CrossRefGoogle Scholar
  43. 43.
    Duh MS, Walker AM, Kronlund KH Jr. Descriptive epidemiology of acute liver enzyme abnormalities in the general population of central Massachusetts. Pharmacoepidemiol Drug Saf. 1999;8:275–83.CrossRefGoogle Scholar
  44. 44.
    Galan MV, Potts JA, Silverman AL, Gordon SC. The burden of acute nonfulminant drug-induced hepatitis in a United States tertiary referral center. J Clin Gastroenterol. 2005;39:64–7.Google Scholar
  45. 45.
    Vuppalanchi R, Liangpunsakul S, Chalasani N. Etiology of new-onset jaundice: how often is it caused by idiosyncratic drug-induced liver injury in the United States. Am J Gastroenterol. 2006;101:1–5.CrossRefGoogle Scholar
  46. 46.
    Jinjuvadia K, Kwan W, Fontana RJ. Searching for a needle in a haystack: use of ICD-9-CM codes in drug-induced liver injury. Am J Gastroenterol. 2007;102:2437–43.CrossRefGoogle Scholar
  47. 47.
    Carey EJ, Vargas HE, Douglas DD, Balan V, Byrne TJ, Harrison ME, et al. Inpatient admissions for drug-induced liver injury: results from a single center. Dig Dis Sci. 2008;53:1977–82.CrossRefGoogle Scholar
  48. 48.
    Orman ES, Conjeevaram HS, Vuppalanchi R, Freston JW, Rochon J, Kleiner DE, et al. Clinical and histopathologic features of fluoroquinolone-induced liver injury. Clin Gastroenterol Hepatol. 2011;9:517–23.CrossRefGoogle Scholar
  49. 49.
    Vuppalanchi R, Hayashi PH, Chalasani N, Fontana RJ, Bonkovsky H, Saxena R, et al. Duloxetine hepatotoxicity: a case-series from the drug-induced liver injury network. Aliment Pharmacol Ther. 2010;32:1174–83.CrossRefGoogle Scholar
  50. 50.
    Molleston JP, Fontana RJ, Lopez MJ, Kleiner DE, Gu J, Chalasani N. Drug-Induced Liver Injury Network characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study. J Pediatr Gastroenterol Nutr. 2011;53:182–9.CrossRefGoogle Scholar
  51. 51.
    Ghabril M, Bonkovsky HL, Kum C, Davern T, Hayashi PH, Kleiner DE, et al. Liver injury from tumor necrosis factor-α antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol. 2013;11(5):558–64.CrossRefGoogle Scholar
  52. 52.
    Russo MW, Hoofnagle JH, Gu J, Fontana RJ, Barnhart H, Kleiner DE, et al. The spectrum of statin hepatotoxicity: experience of the drug induced liver injury network. Hepatology. 2014;60(2):679–8.CrossRefGoogle Scholar
  53. 53.
    Martinez MA, Vuppalanchi R, Fontana RJ, Stolz A, Kleiner DE, Hayashi PH, et al. Clinical and histologic features of azithromycin-induced liver injury. Clin Gastroenterol Hepatol. 2015;13(2):369–76.CrossRefGoogle Scholar
  54. 54.
    Alqahtani SA, Kleiner DE, Ghabril M, Gu J, Hoofnagle JH, Rockey DC. Drug-Induced Liver Injury Network Study Investigators. Identification and characterization of cefazolin-induced liver injury. Clin Gastroenterol Hepatol. 2015;13(7):1328–36.CrossRefGoogle Scholar
  55. 55.
    Goldberg DS, Forde KA, Carbonari DM, Lewis JD, Leidl KB, Reddy KR, et al. Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system. Gastroenterology. 2015;148:1353–61.CrossRefGoogle Scholar
  56. 56.
    Ettel M, Gonzalez GA, Gera S, Eze O, Sigal S, Park JS, et al. Frequency and pathological characteristics of drug-induced liver injury in a tertiary medical center. Hum Pathol. 2017;68:92–8.CrossRefGoogle Scholar
  57. 57.
    Takikawa H, Murata Y, Horiike N, Fukui H, Onji M. Drug-induced liver injury in Japan: an analysis of 1676 cases between 1997 and 2006. Hepatol Res. 2009;39:427–31.CrossRefGoogle Scholar
  58. 58.
    Kwon H, Lee SH, Kim SE, Lee JH, Jee YK, Kang HR, et al. Spontaneously reported hepatic adverse drug events in Korea: multicenter study. J Korean Med Sci. 2012;27:268–73.CrossRefGoogle Scholar
  59. 59.
    Ou P, Chen Y, Li B, Zhang M, Liu X, Li F, et al. Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital. Springerplus. 2015;4:802.  https://doi.org/10.1186/s40064-015-1600-8.eCollection2015.CrossRefGoogle Scholar
  60. 60.
    •• Zhou Y, Yang L, Liao Z, He X, Zhou Y, Guo H. Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients. Eur J Gastroenterol Hepatol. 2013;25:825–9. The largest DILI cohorted reported to date. Patients had better prognosis than previously reported in other DILI cohorts. CrossRefGoogle Scholar
  61. 61.
    Wang GQ, Deng YQ, Hou FQ. Overview of drug-induced liver injury in China. Clin Liver Dis. 2014;4:26–9.CrossRefGoogle Scholar
  62. 62.
    Sobhonslidsuk A, Poovorawan K, Soonthornworasiri N, Pan-Ngum W, Phaosawasdi K. The incidence, presentation, outcomes, risk of mortality and economic data of drug-induced liver injury from a national database in Thailand: a population-base study. BMC Gastroenterol. 2016;16:135.CrossRefGoogle Scholar
  63. 63.
    Jaiprakash H, Narayana S, Mohanraj J. Drug-induced hepatotoxicity in a tertiary care hospital in rural South India. N Am J Med Sci. 2012;4:90–3.CrossRefGoogle Scholar
  64. 64.
    Lee CH, Wang JD, Chen PC. Case-crossover design: an alternative strategy for detecting drug-induced liver injury. J Clin Epidemiol. 2012;65:560–7.CrossRefGoogle Scholar
  65. 65.
    Rathi C, Pipaliya N, Patel R, Ingle M, Phadke A, Sawant P. Drug induced liver injury at a tertiary hospital in India: etiology, clinical features and predictors of mortality. Ann Hepatol. 2017;16:442–50.CrossRefGoogle Scholar
  66. 66.
    Devarbhavi H. Ayurvedic and herbal medicine-induced liver injury: it is time to wake up and take notice. Indian J Gastroenterol. 2018;37:5–7.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculty of Medicine, University of IcelandThe National University Hospital of IcelandReykjavikIceland
  2. 2.Department of Internal Medicine and Division of Gastroenterology and HepatologyThe National University Hospital of IcelandReykjavikIceland
  3. 3.Faculty of MedicineThe National University Hospital of IcelandReykjavikIceland

Personalised recommendations