Review article: Drug-induced liver injury - Its pathophysiology and evolving diagnostic tools

Alimentary Pharmacology and Therapeutics

Volumn 34, Issue 1, 2011, Pages 11-20

  Au, J S ^a   Navarro, V J ^a   Rossi, S ^a  

^a THOMAS JEFFERSON UNIVERSITY HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; AMINOTRANSFERASE; AMIODARONE; AMOXICILLIN PLUS CLAVULANIC ACID; BROMOBENZENE; BUPIVACAINE; CYTOCHROME P450; DIBENZODIOXIN DERIVATIVE; DICLOFENAC; DIOXIN; FLUCLOXACILLIN; GALACTOSAMINE; HLA B ANTIGEN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISONIAZID; MEVALONIC ACID; MICRORNA; PARACETAMOL; PLACEBO; PRAVASTATIN; PROCAINAMIDE; SULFONAMIDE; TETRACYCLINE; VALPROIC ACID; XIMELAGATRAN;

CLINICAL TRIAL (TOPIC); DIAGNOSTIC PROCEDURE; DRUG BLOOD LEVEL; DRUG HYPERSENSITIVITY; DRUG MEGADOSE; DRUG TISSUE LEVEL; DRUG URINE LEVEL; GENETIC ASSOCIATION; HUMAN; LIVER INJURY; LIVER TOXICITY; METABOLOMICS; NONHUMAN; PATHOPHYSIOLOGY; PHARMACOGENETICS; PRIORITY JOURNAL; PROTEOMICS; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMATIC REVIEW; TOXIC HEPATITIS; TOXICOGENETICS; TRANSCRIPTOMICS;

DRUG-INDUCED LIVER INJURY; HUMANS; LIVER; LIVER FAILURE; PHARMACEUTICAL PREPARATIONS; PHARMACOGENETICS;

EID: 79958175637     PISSN: 02692813     EISSN: 13652036     Source Type: Journal    
DOI: 10.1111/j.1365-2036.2011.04674.x     Document Type: Review

References (76)

1. Ostapowicz G, Fontana RJ, Schiodt FV, 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. (Pubitemid 35440240)
2. Larry D,. Epidemiology and individual susceptibility to adverse drug reaction affecting the liver. Semin Liver Dis 2002; 22: 145-55.
3. Rowden AK, Norvell J, Eldridge DL, Kirk MA,. Updates on acetaminophen toxicity. Med Clin North Am 2005; 89: 1145-59. (Pubitemid 41446566)
4. Navarro VJ, Senior JR,. Drug related hepatotoxicity. N Engl J Med 2006; 35: 731-9.
5. Abboud G, Kaplowitz N,. Drug-induced liver injury. Drug Saf 2007; 30: 277-94. (Pubitemid 46624528)
6. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH,. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002; 287: 2215-20. (Pubitemid 34441937)
7. Grattagliano I, Bonfrate L, Diogo CV, Wang HH, Wang DQH, Portincasa P,. Biochemical mechanisms in drug-induced liver injury: certainties and doubts. World J Gastroenterol 2009; 15: 4865-76.
8. Kaplowitz N,. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov 2005; 4: 489-99. (Pubitemid 40861991)
9. Boelsterli UA,. Mechanisms of NSAID-induced hepatotoxicity: focus on nimesulide. Drug Saf 2002; 25: 633-48.
10. Russmann S, Kullak-Ublick GA, Grattagliano I,. Current concepts of mechanisms in drug-induced hepatotoxicity. Curr Med Chem 2009; 16: 3041-53.
11. Robin MA, Le Roy M, Descatoire V, Pessayer D,. Plasma membrane cytochromes P450 as neoantigens and autoimmune targets in drug-induced hepatitis. J Hepatol 1997; 26: 23-30. (Pubitemid 127777234)
12. Uetrecht J,. New concepts in immunology relevant to idiosyncratic drug reactions: the 'danger hypothesis' and innate immune system. Chem Res Toxicol 1999; 12: 387-95. (Pubitemid 29352401)
13. Park BK, Kitteringham NR, Powell H, Pirmohamed M,. Advances in molecular toxicology-towards understanding idiosyncratic drug toxicity. Toxicology 2000; 153: 39-60.
14. Matzinger P,. An innate sense of danger. Immunology 1998; 10: 399-415. (Pubitemid 28499554)
15. Luyendyk JP, Maddox JF, Cosma GN, Ganey PE, Cockerell GL, Roth RA,. Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats. J Pharmacol Exp Ther 2003; 307: 1227-34.
16. Malhi H, Gores GJ,. Cellular and molecular mechanisms of liver injury. Gastroenterology 2008; 134: 1641-54. (Pubitemid 351615416)
17. Kaplowitz N,. Biochemical and cellular mechanisms of toxic liver Injury. Semin Liver Dis 2002; 22: 137-44. (Pubitemid 34496467)
18. Kopanoff DE, Snider DE Jr, Caras GJ,. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis 1978; 117: 991-1001. (Pubitemid 8380195)
19. Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW,. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. J Am Med Assoc 1994; 271: 992-8. (Pubitemid 24099919)
20. Summers WK, Koehler AL, Marsh GM, Tachiki K, Ling A,. Long-term hepatotoxicity of tacrine. Lancet 1989; 1: 729.
21. Lee WM, Larrey D, Olsson R, et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf 2005; 28: 351-70. (Pubitemid 40545769)
22. Watkins PB, Whitcomb RW,. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998; 338: 916-7.
23. Nukaya M, Walisser JA, Moran SM, Kennedy GD, Bradfield CA,. Aryl hydrocarbon receptor nuclear translocator in hepatocytes is required for aryl hydrocarbon receptor-mediated adaptive and toxic responses in liver. Toxicol Sci 2010; 118: 554-63.
24. Aleksunes LM, Campion SN, Goedken MJ, Manautou JE,. Acquired resistance to acetaminophen hepatotoxicity is associated with induction of multidrug resistance-associated protein 4 (MRP4) in proliferating hepatocytes. Toxicol Sci 2008; 104: 261-73. (Pubitemid 352038249)
25. Chan K, Han XD, Kan YW,. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci USA 2001; 98: 4611-6. (Pubitemid 32295024)
26. Okawa H, Motohashi H, Kobayashi A, Aburatani H, Kensler TW, Yamamoto M,. Hepatocyte-specific deletion of the Keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem Biophys Res Commun 2006; 339: 79-88. (Pubitemid 41697517)
27. Shayiq RM, Roberts DW, Rothstein K, et al. Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: an explanation for high acetaminophen dosage in humans without hepatic injury. Hepatology 1999; 29: 451-63. (Pubitemid 29088449)
28. Furberg CD, Adams HP Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) research group. Circulation 1994; 90: 1679-87. (Pubitemid 24320914)
29. Bhardwaj S, Chalasani N,. Lipid-lowering agents that cause drug-induced hepatotoxicity. Clin Liver Dis 2007; 11: 597-613. (Pubitemid 47304463)
30. Kornbrust DJ, MacDonald JS, Peter CP, et al. Toxicity of the HMG-coenzyme A reductase inhibitor, lovastatin, to rabbits. J Pharmacol Exp Ther 1989; 248: 498-505. (Pubitemid 19090215)
31. Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol 1997; 80: 278-86. (Pubitemid 27330142)
32. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S). Lancet 1994; 344: 1383-9.
33. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349-57.
34. Lewis JH, Mortensen ME, Zweig S, et al. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 2007; 46: 1453-63. (Pubitemid 350155527)
35. Li AP,. 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 2002; 142: 7-23. (Pubitemid 35232550)
36. Fontana RJ, Watkins PB, Bonkovsky HL, et al. Drug-induced liver injury network (DILIN) prospective study: rationale, design and conduct. Drug Saf 2009; 32: 55-68.
37. Russman S, Jetter A, Kullak-Ublick GA,. Pharmacogenetics of drug-induced liver injury. Hepatology 2010; 52: 748-61.
38. Daly AK, Chris DP,. Genetic association studies in drug-induced liver injury. Semin Liver Dis 2009; 29: 400-11.
39. Huang YS, Su WJ, Huang YH, et al. Genetic Polymorphisms of manganese superoxide dismutase, NAD(P)H:quinone oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury. J Hepatol 2007; 47: 128-34.
40. Spielberg SP,. In vitro assessment of pharmacogenetic susceptibility to toxic drug metabolites in humans. Fed Proc 1984; 43: 2308-13. (Pubitemid 14107560)
41. 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: 435-55. (Pubitemid 36549828)
42. Hickman D, Sim E,. N-acetyltransferase polymorphism comparison of phenotype and genotype in humans. Biochem Pharmacol 1991; 42: 1007-14.
43. Huang YS, Chern HD, Su WJ, et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for anti-tuberculosis drug-induced hepatitis. Hepatology 2002; 35: 883-9.
44. Daly AK, Aithal GP, Leathart JB, Swainsbury RA, Dang TS, Day CP,. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology 2007; 132: 272-81. (Pubitemid 46108755)
45. 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: 1603-12. (Pubitemid 38702661)
46. 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: 816-21.
47. Kindmark A, Jawaid A, Harbron CG, et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests and underlying immune pathogenesis. Pharmacogenetics J 2008; 8: 186-95. (Pubitemid 351712643)
48. Hautekeete ML, Horsmans Y, Van Waeyenberge C, et al. HLA association of amoxicillin-clavulanate-induced hepatitis. Gatreoenterology 1999; 117: 1181-6. (Pubitemid 29512678)
49. O'Donohue J, Oien KA, Donaldson P, et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut 2000; 47: 717-20.
50. 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: 1049-53.
51. Mallal S, Phillips E, Carosi G, et al. PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008; 358: 568-79. (Pubitemid 351214284)
52. Aardema MJ, MacGregor JT,. Toxicology and genetic toxicology in the new era of 'toxicogenomics;' impact of 'omics' technologies. Mutat Res 2002; 499: 13-25. (Pubitemid 34137071)
53. Amacher DE,. The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity. Toxicol Appl Pharmacol 2010; 245: 134-42.
54. Stierum R, Heijne W, Kienhuis A, van Ommen B, Groten J,. Toxicogenomics concepts and applications to study hepatic effects of food additives and chemicals. Toxicol Appl Pharmacol 2005; 207: S179-88. (Pubitemid 41265512)
55. Andersson U, Lindberg J, Wang S, et al. A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran. Biomarkers 2009; 14: 572-86.
56. Nicholson JK, Connelly J, Lindon JS, Holmes E,. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 2002; 1: 153-61. (Pubitemid 41646523)
57. O'Connell TM, Watkins PB,. The application of metabonomics to predict drug-induced liver injury. Clin Pharmacol Ther 2010; 88: 394-9.
58. Lindon JC, Keun HC, Ebbels TM, Pearce JM, Holmes E, Nicholson JK,. The consortium for metabolic toxicology (COMET): aims, activities, and achievements. Pharmacogenomics 2005; 6: 691-9. (Pubitemid 41479414)
59. Lindon JC, Nicholson JK, Holmes E, et al. Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol Appl Pharmacol 2003; 187: 137-46. (Pubitemid 36349345)
60. Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK,. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci USA 2009; 106: 14728-33.
61. Winnike JH, Li Z, Wright FA, Macdonald JM, O'Connell TM, Watkins PB,. Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans. Clin Pharmacol Ther 2010; 88: 45-51.
62. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105: 10513-8.
63. Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18: 997-1006.
64. Wang GK, Zhu JQ, Zhang JT, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010; 31: 659-66.
65. Wang K, Zhang S, Marzolf B, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009; 106: 4402-7.
66. Wetmore BA, Brees DJ, Singh R, et al. Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury. Hepatology 2010; 51: 2127-39.
67. Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 2010; 56: 1830-8.
68. Wong LL, Fan ST, Man K, et al. Identification of liver proteins and their roles associated with carbon tetrachloride-induced hepatotoxicity. Hum Exp Toxicol [Epub ahead of print].
69. Van Summeren A, Renes J, Bouwman FG, et al. Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci 2011; 120: 109-22.
70. Yamamoto T, Kikkawa R, Yamada H, Horii I,. Identification of oxidative stress-related proteins for predictive screening of hepatotoxicity using a proteomic approach. J Toxicol Sci 2005; 30: 213-27. (Pubitemid 41305779)
71. Witzmann FA, Clack JW, Geiss K, et al. Proteomic evaluation of cell preparation methods in primary hepatocyte cell culture. Electrophoresis 2002; 23: 2223-32.
72. Amacher DE, Adler R, Herath A, Townsend RR,. Use of proteomic methods to identify serum biomarkers associated with rat liver toxicity or hypertrophy. Clin Chem 2005; 51: 1796-803. (Pubitemid 41368169)
73. Ruepp SU, Tonge RP, Shaw J, Wallis N, Pognan F,. Genomics and proteomics analysis of acetaminophen toxicity in mouse liver. Toxicol Sci 2002; 65: 135-50. (Pubitemid 34092698)
74. Heijne WH, Stierum RH, Slijper M, van Bladeren PJ, van Ommen B,. Toxicogenomics of bromobenzene hepatotoxicity: a combined transcriptomics and proteomics approach. Biochem Pharmacol 2003; 65: 857-75. (Pubitemid 36293702)
75. Heijne WH, Slitt AL, van Bladeren PJ, et al. Bromobenzene-induced hepatotoxicity at the transcriptome level. Toxicol Sci 2004; 79: 411-22. (Pubitemid 38786898)
76. Schnackenberg LK, Jones RC, Thyparambil S, et al. An integrated study of acute effects of valproic acid in the liver using metabonomics, proteomics, and transcriptomics platforms. OMICS 2006; 10: 1-14.