Digestive Diseases and Sciences

, Volume 52, Issue 10, pp 2463–2471 | Cite as

Drug-Induced Liver Injury: Review Article

  • Wissam BleibelEmail author
  • Stephen Kim
  • Karl D’Silva
  • Eric R. Lemmer
Review Article

Drug-induced liver injury (DILI) is a term that describes abnormalities in liver function tests (LFTs) related to medication intake. DILI, a subtype of hepatotoxicity, does not include hepatic injuries related to nonmedicinal compounds, including herbal, complementary, and alternative medicines [1, 2].

DILI accounts for roughly 0.1% to 3% of hospital admissions, 600 liver transplantations, and 120 deaths from liver failure in the United States each year [3, 4, 5, 6]. It is the Number 1 cause of death from acute liver failure in the country [3], and the most frequent cause of medication withdrawal from the market [7].

The liver is the central organ in the metabolism and detoxification of drugs and toxins. Consequently, drugs affect the liver more frequently than any other organ and place the liver at increased risk for toxic damage [8]. After absorption by the intestines, drugs reach the liver via the portal system. In the hepatocytes, these chemicals undergo complex metabolic...


Drug-induced liver injury Hepatotoxicity 


  1. 1.
    Velayudham LS, Farrell GC (2003) Drug-induced cholestasis. Expert Opin Drug Saf 2:287–304PubMedCrossRefGoogle Scholar
  2. 2.
    Benichou C (1990) Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 11:272–276PubMedCrossRefGoogle Scholar
  3. 3.
    Lazerow SK, Abdi MS, Lewis JH (2005) Drug-induced liver disease 2004. Curr Opin Gastroenterol 21:283–292PubMedCrossRefGoogle Scholar
  4. 4.
    Lee WM, Senior JR (2005) Recognizing drug-induced liver injury: current problems, possible solutions. Toxicol Pathol 33:155– 164PubMedCrossRefGoogle Scholar
  5. 5.
    Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279:1200–1205PubMedCrossRefGoogle Scholar
  6. 6.
    Hartleb M, Biernat L, Kochel A (2002) Drug-induced liver damage: a three-year study of patients from one gastroenterological department. Med Sci Monit 8:CR292—CR296PubMedGoogle Scholar
  7. 7.
    Lee WM (2003) Drug-induced hepatotoxicity (review). N Engl J Med 349:474–485PubMedCrossRefGoogle Scholar
  8. 8.
    Bussieres JF, Habra M (1995) Application of International Consensus Meeting Criteria for classifying drug-induced liver disorders. Ann Pharmacother 29:875–878PubMedGoogle Scholar
  9. 9.
    Park BK, Kitteringham NR, Maggs JL, Pirmohamed M, Williams DP (2005) The role of metabolic activation in drug-induced hepatotoxicity. Annu Rev Pharmacol Toxicol 45:177–202PubMedCrossRefGoogle Scholar
  10. 10.
    Gunawan B, Kaplowitz N (2004) Clinical perspectives on xenobiotic-induced hepatotoxicity. Drug Metab Rev 36:301–312PubMedCrossRefGoogle Scholar
  11. 11.
    Galan MV, Potts JA, Silverman AL, Gordon SC (2005) Hepatitis in a United States tertiary referral center. J Clin Gastroenterol 39:64–67PubMedGoogle Scholar
  12. 12.
    Duh MS, Walker AM, Kronlund KH, Jr. (1999) Descriptive epidemiology of acute liver enzyme abnormalities in the general population of central Massachusetts. Pharmacoepidemiol Drug Saf. 8:275—283CrossRefGoogle Scholar
  13. 13.
    Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, Lenoir C, Lemoine A, Hillon P (2002) Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology 36:451–455PubMedCrossRefGoogle Scholar
  14. 14.
    Lewis JH (2002) The rational use of potentially hepatotoxic medications in patients with underlying liver disease. Expert Opin Drug Saf 1:159–172PubMedCrossRefGoogle Scholar
  15. 15.
    Aithal PG, Day CP (1999) The natural history of histologically proved drug induced liver disease. Gut 44:731–735PubMedCrossRefGoogle Scholar
  16. 16.
    Rashid M, Goldin R, Wright M (2004) Drugs and the liver. Hosp Med 65:456–461PubMedGoogle Scholar
  17. 17.
    Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P (2004) Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl 10:1018–1023PubMedCrossRefGoogle Scholar
  18. 18.
    Li AP (2002) A review of the common properties of drugs with idiosyncratic hepatotoxicity and the “multiple determinant hypothesis” for the manifestation of idiosyncratic drug toxicity. Chem Biol Interact 142:7–23PubMedCrossRefGoogle Scholar
  19. 19.
    Ju C (2005) Immunological mechanisms of drug-induced liver injury. Curr Opin Drug Discov Devel 8:38–43PubMedGoogle Scholar
  20. 20.
    Cullen JM (2005) Mechanistic classification of liver injury. Toxicol Pathol 33:6–8PubMedCrossRefGoogle Scholar
  21. 21.
    Mackay IR (1999) Immunological perspectives on chronic hepatitis: virus infection, autoimmunity and xenobiotics. Hepatogastroenterology 46:3021–3033PubMedGoogle Scholar
  22. 22.
    Kaplowitz N (2002) Biochemical and cellular mechanisms of toxic liver injury. Semin Liver Dis 22:137–144PubMedCrossRefGoogle Scholar
  23. 23.
    Holt MP, Ju C (2006) Mechanisms of drug-induced liver injury. AAPS J 8:E48–E54PubMedCrossRefGoogle Scholar
  24. 24.
    Kaplowitz N (2004) Drug-induced liver injury. Clin Infect Dis 38(Suppl 2):S44–S48PubMedCrossRefGoogle Scholar
  25. 25.
    Maddrey WC (2005) Drug-induced hepatotoxicity: 2005. J Clin Gastroenterol 39(4 Suppl 2):S83–S89PubMedCrossRefGoogle Scholar
  26. 26.
    Aithal GP (2004) Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. Expert Opin Drug Saf 3:519–523PubMedCrossRefGoogle Scholar
  27. 27.
    Russo MW, Watkins PB (2004) Are patients with elevated liver tests at increased risk of drug-induced liver injury? Gastroenterology 126:1477–1480PubMedCrossRefGoogle Scholar
  28. 28.
    Watkins PB (2005) Idiosyncratic liver injury: challenges and approaches. Toxicol Pathol 33:1–5PubMedCrossRefGoogle Scholar
  29. 29.
    Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N (1995) Fulminant hepatic failure: summary of a workshop. Hepatology 21:240–252PubMedGoogle Scholar
  30. 30.
    Amacher DE (2002) A toxicologist’s guide to biomarkers of hepatic response. Hum Exp Toxicol 21:253–262PubMedCrossRefGoogle Scholar
  31. 31.
    Hoofnagle JH (2004) Drug-induced liver injury network (DILIN). Hepatology 40:773PubMedGoogle Scholar
  32. 32.
    Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM; U.S. Acute Liver Failure Study Group (2002) Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 137:947–954PubMedGoogle Scholar
  33. 33.
    Sniderman AD (2004) Is there value in liver function test and creatine phosphokinase monitoring with statin use? Am J Cardiol 94:30F–33FPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Wissam Bleibel
    • 1
    Email author
  • Stephen Kim
    • 2
  • Karl D’Silva
    • 1
  • Eric R. Lemmer
    • 3
  1. 1.Caritas Carney Hospital/Tufts UniversityBostonUSA
  2. 2.Tufts University School of MedicineBostonUSA
  3. 3.HCC Research Program Mount Sinai School of Medicine, Division of Liver DiseasesNew YorkUSA

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