Biomarkers for the diagnosis and management of drug-induced liver injury

Seminars in Liver Disease

Volumn 29, Issue 4, 2009, Pages 393-399

  Watkins, Paul B ^a,b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b HAMNER INSTITUTES FOR HEALTH SCIENCES   (United States)

Author keywords

Adaptation; Biomarkers; Genomics; Lymphocyte transformation test; Metabolomics; Pharmacogenetics; Proteomics; Transcriptomics

Indexed keywords

ALANINE AMINOTRANSFERASE; BILIRUBIN; BIOLOGICAL MARKER; DIHYDRALAZINE; FIALURIDINE; FLUCLOXACILLIN; HALOTHANE; HEPARIN; HLA B ANTIGEN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISONIAZID; LIVER KIDNEY MICROSOMAL ANTIBODY; MICROSOME ANTIBODY; NEFAZODONE; PARACETAMOL; TACRINE; TIENILIC ACID; TROGLITAZONE; UNCLASSIFIED DRUG; XIMELAGATRAN;

ABDOMINAL PAIN; ADAPTATION; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALZHEIMER DISEASE; ARTICLE; BILIRUBIN BLOOD LEVEL; DRUG INDUCED DISEASE; DRUG WITHDRAWAL; FATIGUE; GENETIC ASSOCIATION; HAPLOTYPE; HEPATITIS; HUMAN; JAUNDICE; LIVER FAILURE; LIVER INJURY; LYMPHOCYTE TRANSFORMATION TEST; METABOLOMICS; NAUSEA; NONHUMAN; POLYPHARMACY; PRIORITY JOURNAL; PROTEOMICS; SIDE EFFECT; TRANSCRIPTOMICS; VALIDATION PROCESS;

ANTIBODIES; BIOLOGICAL MARKERS; DIAGNOSIS, DIFFERENTIAL; DIAGNOSTIC TESTS, ROUTINE; DRUG-INDUCED LIVER INJURY; GENETIC TESTING; GENOMICS; HUMANS; LYMPHOCYTE ACTIVATION; METABOLOMICS; PREDICTIVE VALUE OF TESTS; PROGNOSIS; PROTEOMICS; REPRODUCIBILITY OF RESULTS;

EID: 70449109529     PISSN: 02728087     EISSN: 10988971     Source Type: Journal    
DOI: 10.1055/s-0029-1240008     Document Type: Article

References (61)

1. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001 69 (3) 89-95
2. Watkins P B., Seeff L B. Drug-induced liver injury: summary of a single topic clinical research conference. Hepatology 2006 43 (3) 618-631
3. Green R M., Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 2002 123 (4) 1367-1384
4. Sayuk G S., Elwing J E., Lisker-Melman M. Hepatic glycogenosis: an underrecognized source of abnormal liver function tests? Dig Dis Sci 2007 52 (4) 936-938
5. Olsson R, Wesslau C, William-Olsson T, Zettergren L. Elevated aminotransferases and alkaline phosphatases in unstable diabetes mellitus without ketoacidosis or hypoglycemia. J Clin Gastroenterol 1989 11 (5) 541-545
6. Rautou P E., Cazals-Hatem D, Moreau R et al. Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy. Gastroenterology 2008 135 (3) 840-848, 848.e1e3
7. Browning J D., Szczepaniak L S., Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004 40 (6) 1387-1395
8. Thulin P, Rafter I, Stockling K et al. PPARalpha regulates the hepatotoxic biomarker alanine aminotransferase (ALT1) gene expression in human hepatocytes. Toxicol Appl Pharmacol 2008 231 (1) 1-9
9. Watkins P B., Zimmerman H J., Knapp M J., Gracon S I., Lewis K W. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA 1994 271 (13) 992-998
10. Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov 2005 4 (6) 489-499
11. Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A. Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia. Eur J Clin Pharmacol 1989 37 (4) 415-418
12. Mitchell J R., Long M W., Thorgeirsson U P., Jollow D J. Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy. Chest 1975 68 (2) 181-190
13. Watkins P B., Whitcomb R W. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998 338 (13) 916-917
14. Lee W M., Larrey D, Olsson R et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf 2005 28 (4) 351-370
15. Torti V R., Cobb A J., Everitt J I., Marshall M W., Boorman G A., Butterworth B E. Nephrotoxicity and hepatotoxicity induced by inhaled bromodichloromethane in wild-type and p53-heterozygous mice. Toxicol Sci 2001 64 (2) 269-280
16. Shayiq R M., Roberts D W., 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 (2) 451-463
17. Aleksunes L M., Campion S N., Goedken M J., Manautou J E. Acquired resistance to acetaminophen hepatotoxicity is associated with induction of multidrug resistance-associated protein 4 (Mrp4) in proliferating hepatocytes. Toxicol Sci 2008 104 (2) 261-273
18. Ros J E., Libbrecht L, Geuken M, Jansen P L., Roskams T A. High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease. J Pathol 2003 200 (5) 553-560
19. Zimmerman H J. The spectrum of hepatotoxicity. Perspect Biol Med 1968 12 (1) 135-161
20. Bjrnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005 42 (2) 481-489
21. Andrade R J., Lucena M I., Kaplowitz N et al. Outcome of acute idiosyncratic drug-induced liver injury: long-term follow-up in a hepatotoxicity registry. Hepatology 2006 44 (6) 1581-1588
22. Pachkoria K, Lucena M I., Molokhia M et al. Genetic and molecular factors in drug-induced liver injury: a review. Curr Drug Saf 2007 2 (2) 97-112
23. Daly A K., Donaldson P T., Bhatnagar P et al, 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 (7) 816-819
24. Hoofnagle J H. Drug-induced liver injury network (DILIN). Hepatology 2004 40 (4) 773
25. Holden A. Detecting and Investigating Drug Induced Adverse Events the International Serious Adverse Event Consortium's Experience to Date. 2008. Available at: http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ ucm077482.pdf Accessed July 10, 2009
26. Webster P A., Roberts D W., Benson R W., Kearns G L. Acetaminophen toxicity in children: diagnostic confirmation using a specific antigenic biomarker. J Clin Pharmacol 1996 36 (5) 397-402
27. Davern T J. II, James L P., Hinson J A. et al, Acute Liver Failure Study Group. Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology 2006 130 (3) 687-694
28. James L P., Capparelli E V., Simpson P M. et al, Network of Pediatric Pharmacology Research Units, National Institutes of Child Health and Human Development. Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose. Clin Pharmacol Ther 2008 84 (6) 684-690
29. James L P., Letzig L, Simpson P M. et al. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos 2009 37 (8) 1779-1784
30. Hinson J A., Reid A B., McCullough S S., James L P. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev 2004 36 (3-4) 805-822
31. Cohen S D., Pumford N R., Khairallah E A. et al. Selective protein covalent binding and target organ toxicity. Toxicol Appl Pharmacol 1997 143 (1) 1-12
32. Antoine D J., Williams D P., Park B K. Understanding the role of reactive metabolites in drug-induced hepatotoxicity: state of the science. Expert Opin Drug Metab Toxicol 2008 4 (11) 1415-1427
33. Pichler W J., Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 2004 59 (8) 809-820
34. Merk H F. Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines. Toxicology 2005 209 (2) 217-220
35. Schreiber J, Zissel G, Greinert U, Schlaak M, Mller-Quernheim J. Lymphocyte transformation test for the evaluation of adverse effects of antituberculous drugs. Eur J Med Res 1999 4 (2) 67-71
36. Maria V A., Victorino R M. Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury. Gut 1997 41 (4) 534-540
37. Kindmark A, Jawaid A, Harbron C G. 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
38. 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
39. Watkins P B. Antimicrosomal antibodies: what are they telling us? Hepatology 1991 13 (2) 385-387
40. Beaune P H., Lecoeur S, Bourdi M et al. Anti-cytochrome P450 autoantibodies in drug-induced disease. Eur J Haematol Suppl 1996 60 89-92
41. Robin M A., Le Roy M, Descatoire V, Pessayre D. Plasma membrane cytochromes P450 as neoantigens and autoimmune targets in drug-induced hepatitis. J Hepatol 1997 26 (Suppl 1) 23-30
42. Obermayer-Straub P, Strassburg C P., Manns M P. Target proteins in human autoimmunity: cytochromes P450 and UDP- glucuronosyltransferases. Can J Gastroenterol 2000 14 (5) 429-439
43. Manns M P., Obermayer-Straub P. Cytochromes P450 and uridine triphosphate-glucuronosyltransferases: model autoantigens to study drug-induced, virus-induced, and autoimmune liver disease. Hepatology 1997 26 (4) 1054-1066
44. Homberg J C., Andre C, Abuaf N. A new anti-liver-kidney microsome antibody (anti-LKM2) in tienilic acid-induced hepatitis. Clin Exp Immunol 1984 55 (3) 561-570
45. Bourdi M, Larrey D, Nataf J et al. Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis. J Clin Invest 1990 85 (6) 1967-1973
46. Nguyen C, Rose N R., Njoku D B. Trifluoroacetylated IgG4 antibodies in a child with idiosyncratic acute liver failure after first exposure to halothane. J Pediatr Gastroenterol Nutr 2008 47 (2) 199-202
47. Beaune P, Dansette P M., Mansuy D et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc Natl Acad Sci U S A 1987 84 (2) 551-555
48. Stoevesandt O, Taussig M J., He M. Protein microarrays: high-throughput tools for proteomics. Expert Rev Proteomics 2009 6 (2) 145-157
49. McKenzie R, Fried M W., Sallie R et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 1995 333 (17) 1099-1105
50. Dykens J A., Jamieson J D., Marroquin L D. et al. In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone. Toxicol Sci 2008 103 (2) 335-345
51. Xu J J., Henstock P V., Dunn M C., Smith A R., Chabot J R., de Graaf D. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol Sci 2008 105 (1) 97-105
52. Nicholson J K., Lindon J C. Systems biology: Metabonomics. Nature 2008 455 (7216) 1054-1056
53. Clayton T A., Lindon J C., Cloarec O et al. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature 2006 440 (7087) 1073-1077
54. Cederbrant K E. Systems biology approach to ximelagatran injury. 2009. Available at: http://www.aasld.org/conferences/educationtraining/Documents/ Hepatoxicity%20Slides/Cederbrant.pdf Accessed July 10, 2009
55. O'Connell T. The application of metabolomics to acetaminophen-induced liver injury in humans. 2009. Available at: http://www.aasld.org/conferences/ educationtraining/Documents/Hepatoxicity%20Slides/Oconnell.pdf Accessed July 10, 2009
56. Blomme E A., Yang Y, Waring J F. Use of toxicogenomics to understand mechanisms of drug-induced hepatotoxicity during drug discovery and development. Toxicol Lett 2009 186 (1) 22-31
57. Bushel P R., Heinloth A N., Li J et al. Blood gene expression signatures predict exposure levels. Proc Natl Acad Sci U S A 2007 104 (46) 18211-18216
58. Wang K, Zhang S, Marzolf B et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A 2009 106 (11) 4402-4407
59. Miyamoto M, Yanai M, Ookubo S, Awasaki N, Takami K, Imai R. Detection of cell-free, liver-specific mRNAs in peripheral blood from rats with hepatotoxicity: a potential toxicological biomarker for safety evaluation. Toxicol Sci 2008 106 (2) 538-545
60. Nolan C M., Goldberg S V., Buskin S E. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA 1999 281 (11) 1014-1018
61. Institute of Medicine. Accelerating the development of biomarkers for drug safety: workshop summary. Available at: http://www.iom.edu/CMS/3740/24155/ 70596.aspx Accessed July 10, 2009