Regulatory perspectives

Drug-Induced Liver Disease

Volumn , Issue , 2013, Pages 689-712

  Avigan, Mark I ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Clinical trials; DILI biomarkers; DILI risk assessment; DILI risk management; Drug induced liver injury (DILI); FDA regulations; Postmarket DILI surveillance tools

Indexed keywords

EID: 84882575529     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-387817-5.00038-8     Document Type: Chapter

References (118)

1. Watkins P.B., Seeff L.B. Drug-induced liver injury: summary of a single topic clinical research conference. Hepatology 2006, 43:618-631.
2. Acetaminophen information. (January 13, 2011). <>; [accessed 10.08.11]. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm .
3. Reuben A., Koch D.G., Lee W.M. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010, 52:2065-2076.
4. PhRMA/FDA/AASLD. Drug-induced hepatotoxicity white paper: postmarketing considerations. <>; 2000 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ucm0914 62.pdf.
5. Olson H., Graham B., Robinson D., Thomas K., Monro K., Loaja G., et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Phamacol 2000, 32:56-67.
6. Watkins P.B. Drug safety sciences and the bottleneck in drug development. Clin Pharmacol Ther 2011, 89:788-790.
7. Chen M., Vijay V., Shi Q., Liu Z., Fang H., Tong W. FDA-approved labeling for the study of drug-induced liver injury. Drug Discovery Today 2011, 16:697-703.
8. Liver Toxicity Knowledge Database (LTKB) Benchmark Dataset. National Center for Toxicological Research. US Food and Drug Administration (FDA). <>; [accessed 10.08.11]. http://www.fda.gov/ScienceResearch/BioinformaticsTools/LiverToxicityKnow ledgeBase/ucm226811.htm.
9. Stevens J.L., Baker T.K. The future of drug safety testing: expanding the view and narrowing the focus. Drug Discovery Today 2009, 14:162-167.
10. Olson S, Robinson S, Giffin R. Institute of Medicine. Accelerating the Development of Biomarkers for Drug Safety: Workshop Summary. National Academies Press. Ibid. Watkins, P.B., Bloom, J., and Hunt, C., Biomarkers of acute idiosyncratic hepatocellular injury in clinical trials. Chapter 5, 2009. p. 42-57.
11. Temple RJ. Welcome to DILI <>; 2011 [accessed 31.10.12]. http://www.aasld.org/meetings/Documents/Hepatotoxicity%20STC/0-1_Temple. pdf.
12. Meadows M. Promoting safe and effective drugs for 100 years. <>; 2006 [accessed 10.08.11]. http://www.fda.gov/AboutFDA/WhatWeDo/History/CentennialofFDA/CentennialE ditionofFDAConsumer/ucm093787.htm.
13. FDA Guidance for Industry. Premarketing risk assessment. <>; 2005 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/UCM072002.pdf.
14. Aithal G.P., Watkins P.B., Andrade R.J., Larrey D., Molokhin M., Takikawa H., et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011, 89:806-815.
15. Senior J.R., Avigan M. Detection of hepatotoxicity during drug development: practical problems and regulatory measures. Hepatotoxicity 2007, 147-166. Permanyer Publications, Barcelona, [International Hepatology Updates. (Ed. V. Arroyo)]. R.J. Andrade (Ed.).
16. Gough A., Chapman S., Wagstaff K., Emery P., Elias E. Minocycline-induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ 1996, 312:169-172.
17. Watkins P.B., Kaplowitz N., Slattery J.T., Colonese C.R., Colucci S.V., Stewart P.W., et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006, 296:87-93.
18. Olsson R., Korsan-Bengtsen B.-M., Korsan-Bengtsen K., Lennartsson J., Waldenstrom J. Serum aminotransferases after low-dose heparin treatment. Acta Med Scand 1978, 204:229-230.
19. 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, 271:992-998.
20. Watkins P.B., Seligman P.J., Pears J.S., Avigan M.I., Senior J.R. Using controlled clinical trials to learn more about acute drug-induced liver injury. Hepatology 2008, 48:1680-1689.
21. Watkins P.B. Biomarkers for the diagnosis and management of drug-induced liver injury. Sem Liv Disease 2009, 29:393-399.
22. Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discovery 2005, 4:489-499.
23. FDA Guidance for Industry. Drug-induced liver injury: pre-marketing clinical evaluation. <>; 2009 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/UCM174090.pdf.
24. Temple R. Hepatotoxicity through the years: impact on the FDA. <>; 2001 [accessed 31.10.12]. http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ucm1221 49.pdf.
25. Reuben A. Hy's law. Hepatology 2004, 39:574-578.
26. Fontana R.J., Seeff L.B., Andrade F.J., Bjornsson E., Day C.P., Serrano J., et al. Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology 2010, 52:730-742.
27. Bjornsson E., Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005, 42:481-489.
28. Andrade R.J., Lucena M.I., Fernandez M.C., Pelaez G., Pachkoria K., Garcia-Ruiz E., Spanish Group for the Study of Drug-Induced Liver Disease, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005, 129:512-521.
29. Rosner B. The binomial distribution. Fundamentals of biostatistics 1995, 82-85. Duxbury Press, Belmont, CA. B. Rosner (Ed.).
30. Goldkind L., Laine L. A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiol Drug Saf 2006, 15:213-220.
31. Knowler W.C., Hamman R.F., Edelstein S.L., Barrett-Conner E., Ehrmann D.A., Walker E.A., et al. Prevention of type 2 diabetes with troglitazone in the diabetes prevention program. Diabetes 2005, 54:1150-1156. The Diabetes Prevention Program Research Group.
32. Graham D.J., Drinkard C.R., Shatin D. Incidence of idiopathic acute liver failure and hospitalized liver injury in patients treated with troglitazone. Am J Gastroenterol 2003, 98:175-179.
33. Gitlin N., Julie N.L., Spurr C.L., Lim K.N., Juarbe H.M. Two cases of severe clinical and histological hepatotoxicity associated with troglitazone. Ann Intern Med 1998, 129:36-38.
34. Graham D.J., Green L., Senior JR., Nourjah P. Troglitazone-induced liver failure: a case study. Am J Med 2003, 114:299-306.
35. Herrine S.K., Choudary C. Severe hepatotoxicity associated with troglitazone. Ann Intern Med 1999, 130:163-164.
36. He R. Clinical review of Exanta (ximelagatran) tablets. <>; 2004 [accessed 10.08.11]. http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4069B1_04_FDA-Backg rounder-MOR-180.pdf.
37. Gelperin K Guo T Senior J. A simple tool for finding important cases in a clinical trial. <>; 2008 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ucm0767 77.pdf.
38. Watkins P.B., Desai M., Berkowitz S.D., Peters G., Horsmans Y., Larrey D., et al. Evaluation of drug-induced serious hepatotoxicity (eDISH): application of this data organization approach to phase III clinical trials of rivaroxaban after total hip or knee replacement surgery. Drug Saf 2011, 34:243-252.
39. Senior J.R., Avigan M. Classification system for likelihood and severity of drug-induced liver injury to score clinical importance of the case. Hepatology 2008, 48:506A.
40. Senior J.R. Monitoring for hepatotoxicity: what is the predictive value of liver "function" tests?. Clin Pharmacol Ther 2009, 85:331-334.
41. Fontana R.J., Watkins P.B., Bonkovsky H.L, Chalasani N., Davern T., Serrano J., for the DILIN Study Group, et al. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf 2009, 32:55-68.
42. Brinker A.D., Wassel R.T., Lyndly J., Serrano J., Avigan M., Lee W.M., et al. Telithromycin-associated hepatotoxicity: clinical spectrum and causality assessment of 42 cases. Hepatology 2009, 49:250-257.
43. Danan G., Benichou C. Causality assessment of adverse reactions to drugs. 1. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993, 46:1323-1330.
44. Hayashi P.H. Causality assessment of drug-induced liver injury. Semin Liver Dis 2009, 29:348-356.
45. Rochon J., Protiva P., Seeff L.B., Fontana R.J., Liangpunsakul S., Watkins P.B., Drug-induced Liver Injury Network (DILIN), et al. Reliability of the Roussel Uclaf causality assessment method for assessing causality in drug-induced liver injury. Hepatology 2008, 48:1175-1183.
46. Rockey D.C., Seeff L.B., Rochon J., Freston J., Chalasani N., Bonacini M., US Drug-Induced Liver Injury Network, et al. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel-Uclaf causality assessment method. Hepatology 2010, 51:2117-2126.
47. Freston JW. Use and limitations of the RUCAM. <>; 2006 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ucm0794 46.pdf.
48. Maria V., Victorino R. Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 1997, 26:664-669.
49. Arimone Y., Bégaud B., Miremont-Salamé G., Fourrier-Réglat A., Molimard M., Moore N., et al. A new method for assessing drug causation provided agreement with experts' judgment. J Clin Epidemiol 2006, 59:308-314.
50. Théophile H., Arimone Y., Miremont-Salamé G., Moore N., Fourrier-Réglat A., Haramburu F., et al. Comparison of three methods (consensual expert judgement, algorithmic and probabilistic approaches) of causality assessment of adverse drug reactions: an assessment using reports made to a French pharmacovigilance centre. Drug Saf 2010, 33:1045-1054.
51. Rowe G., Wright G. The Delphi technique as a forecasting tool: issues and analysis. Int J Forecasting 1999, 15:353-375.
52. Senior JR. Why is the probable cause so important? <>; 2011 [accessed 10.08.11]. http://www.aasld.org/meetings/Documents/Hepatotoxicity%20STC/1A-2_Senior 11.pdf.
53. Lee WM. Characteristics of the ALF population. <>; 2011 [accessed 10.08.11]. http://www.aasld.org/meetings/Documents/Hepatotoxicity%20STC/1B-3_Lee.pd f.
54. Hadem J., Stiefel P., Bahr M.J., Tillmann H.L., Rifai K., Klempnauer J., et al. Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure. Clin Gastroenterol Hepatol 2008, 6:339-345.
55. Ostapowicz G., Fontana R.J., Schiødt F.V., Larson A., Davern T.J., Han S.H., Acute Liver Failure Study Group, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002, 137:947-954.
56. Davern T.J., Chalasani N., Fontana R.J., Hayashi P.H., Protiva P., Kleiner D.E., et al. Drug-Induced Liver Injury Network (DILIN). Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology 2011, 141(5):1665-1672.
57. Weaver J., Willy M., Avigan M. Informatic tools and approaches in postmarketing pharmacovigilance used by FDA. AAPS J 2008, 10:35-41.
58. Weaver J., La Grenade L., Kwon H., Avigan M. Finding, evaluating, and managing drug-related risks: approaches taken by the US Food and Drug Administration (FDA). Dermatol Ther 2009, 22:204-215.
59. Ahmad S.R., Goetsch R.A., Marks N.S. Spontaneous reporting in the United States. Pharmacoepidemiology 2005, 135-159. John Wiley & Sons, Ltd., West Sussex, England. 4th ed. B.L. Strom (Ed.).
60. Lee W.M., Senior J.R. Recognizing drug-induced liver injury: current problems, possible solutions. Toxicol Pathol 2005, 33:155-164.
61. Evans S.J.W., Waller P.C., Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf 2001, 10:483-486.
62. Almenoff J.S., Pattishall E.N., Gibbs T.G., DuMouchel W., Evans S.J., Yuen N. Novel statistical tools for monitoring the safety of marketed drugs. Clin Pharmacol Ther 2007, 82:157-166.
63. Eudravigilance Expert Working Group. Guideline on the use of statistical signal detection methods in the Eudravigilance data analysis system. Adopted by the Committee for Medicinal Products for Human Use (CHMP). June 26, 2008. European Medicines Agency. 7 Westferry Circus, Canary Wharf, London, UK. <>; [accessed 10.08.11]. http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_proc edural_guideline/2009/11/WC500011434.pdf.
64. Hoofnagle J. "Liver Tox"-A new resource from the National Library of Medicine. <>; 2011 [accessed 10.08.11]. http://www.aasld.org/meetings/Documents/Hepatotoxicity%20STC/1B-1_Hoofna gle.pdf.
65. Agarwal V.K., McHutchison J.G., Hoofnagle J.H., for the Drug-Induced Liver Injury Network Important elements for the diagnosis of drug-induced liver injury. Clin Gastroenterol Hepatol 2010, 8:463-470.
66. 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, 36:451-455.
67. Hussaini S.H., O'Brien C.S., Despott E.J., Dalton H.R. Antibiotic therapy: a major cause of drug-induced jaundice in southwest England. Eur J Gastroenterol Hepatol 2007, 19:15-20.
68. Jinjuvadia K., Kwan W., Fontana R.J. Searching for a needle in a haystack: use of ICD-9-CM codes in drug-induced liver injury. Am J Gastroenterol 2007, 102:2437-2443.
69. de Abajo F.J., Montero D., Madurga M., Garcia Rodriguez L.A. Acute and clinically relevant drug-induced liver injury: a population based case-control study. Br J Clin Pharmacol 2004, 58:71-80.
70. Graham D.J., Mosholder A.D., Gelperin K., Avigan M.I. Pharmacoepidemiology and risk management. Pharmacoepidemiology 2005, 515-530. John Wiley & Sons, Ltd., West Sussex, England. 4th ed. B.L. Strom (Ed.).
71. Willy M., Li Z. What is prescription labeling communicating to doctors about hepatotoxic drugs? A study of FDA approved product labeling. Pharmacoepidemiol Drug Saf 2004, 13:201-206.
72. FDA Draft Guidance. Format and content of proposed risk evaluation and mitigation strategies (REMS), REMS assessments, and proposed REMS modifications. <>; 2009 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/UCM184128.pdf.
73. Avigan M. Drug-induced liver injury: epidemiology and considerations of risk. Presentation to American Thyroid Association 2009, ; [accessed 10.08.11].
74. Graham D., Drinkard C.R., Shatin D., Tsong Y., Burgess M.J. Liver enzyme monitoring in patients treated with troglitazone. JAMA 2001, 286:831-833.
75. Walker A.M., Bortnichak E.A., Lanza L., Yood R.A. The infrequency of liver function testing in patients using nonsteroidal anti-inflammatory drugs. Arch Fam Med 1995, 4:24-29.
76. Avigan M. Case study: ximelagatran hepatotoxicity. <>; 2005 [accessed 10.08.11]. http://www.fda.gov/downloads/Drugs/ScienceResearch/../ucm080355.ppt.
77. American Thoracic Society and the Centers for Disease Control and Prevention: Joint statement Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000, 161:S221-S247.
78. 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, 281:1014-1018.
79. Actos (pioglitazone hydrochloride) FDA-approved product label (4 August 2011) <>; [accessed 20.08.11]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021073s043s0441 bl.pdf.
80. Avandia (rosiglitazone maleate). FDA-approved product label (18 May 2011), >; [accessed 20.08.11]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021071s0391bl.p df.
81. Ballet F. Hepatotoxicity in drug development: detection, significance and solutions. J Hepatol 1997, 26:26-36.
82. Daly A.K., Day C.P. Genetic association studies in drug-induced liver injury. Semin Liver Dis 2009, 29:400-411.
83. Lucena M.I., Molokhia M., Shen Y., Urban T.J., Aithal G.P., Andrade R.J., Spanish DILI Registry, EUDRAGENE, DILIN, DILIGEN, and International SAEC, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology 2011, 141:338-347.
84. Daly A.K., Donaldson P.T., Bhatnagar P., Shen Y., Pe'er I., Floratos A., for the DILIGEN study and International SAE Consortium, et al. HLA-B 5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009, 41:816-819.
85. Russman S., Jetter A., Kullak-Ublick G.A. Pharmacogenetics of drug-induced liver injury. Hepatology 2010, 52:748-761.
86. Aithal G.P., Daly A.K. Pre-empting and preventing drug-induced liver injury. Nat Genet 2010, 42:650-651.
87. Manolio T.A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A., Hunter D.J., et al. Finding the missing heritability of complex diseases. Nature 2009, 461:747-753.
88. Avigan M.I. Pharmacogenomic biomarkers of susceptibility to adverse drug reactions: just around the corner or pie in the sky?. Pers Med 2009, 6:67-78.
89. Carbamazepine. FDA information for healthcare professionals. (12 Dec 2007). <>; [accessed 20.08.11]. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPa tientsandProviders/ucm124718.htm.
90. Abacavir. FDA information for healthcare professionals. (24 July 2008). <>; [accessed 20.08.11]. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPa tientsandProviders/ucm123927.htm.
91. Tegretol (carbamazepine USP) FDA-approved product label. <>; [accessed 20.08.11]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/016608s0981bl.p df.
92. Ziagen (abacavir sulfate) FDA-approved product label (19 December 2008) <>; [accessed 20.08.11]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020977s019,0209 78s0221bl.pdf.
93. Stewart J.D., Horvath R., Baruffini E., Ferrero I., Bulst S., Watkins P.B., et al. Polymerase γ gene POLG determines the risk of sodium valproate-induced liver toxicity. Hepatology 2010, 52:1791-1796.
94. Cohen B.H., Naviaux R.K. The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders. Methods 2010, 51:364-373.
95. Krahenbuhl S., Brandner S., Kleinle S., Liechti S., Straumann D. Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure. Liver 2000, 20:346-348.
96. Foundation for the National Institutes of Health Biomarkers Consortium. <>; [accessed 20.08.11]. http://www.biomarkersconsortium.org/.
97. FDA Critical Path Initiative. >; [accessed 20.08.11]. http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/ default.htm.
98. FDA Draft Guidance for Industry. Clinical pharmacogenomics: premarketing evaluation in early phase clinical studies. <>; 2011 [accessed 20.08.11]. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/UCM243702.pdf.
99. FDA Draft Guidance for Industry. Pharmacogenomic data submissions. <>; 2005 [accessed 20.08.11]. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/ucm079849.pdf.
100. FDA Draft Guidance for Industry. Qualification process for drug development tools. <>; 2010 [accessed 20.08.11]. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/UCM230597.pdf.
101. CDER Biomarker Qualification Program. <>; [accessed 28.02.12]. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentTools QualificationProgram/ucm284076.htm.
102. Meyer B.M. The Food and Drug Administration Amendment Act of 2007: drug safety and health-system pharmacy implications. Am J Health Syst Pharm 2009, 66:S3-S5.
103. FDA: Drug Safety Communications. <>; [accessed 20.08.11]. http://www.fda.gov/Drugs/DrugSafety/ucm199082.htm.
104. Murphy S., Roberts R. "Black box" 101: how the Food and Drug Administration evaluates, communicates and manages drug benefit/risk. J Allergy Clin Immunol 2006, 117:34-39.
105. FDA Drug Safety Communication (4 March 2011): Removal of liver injury warning in Letairis (ambrisentan) product label. <>; [accessed 20.08.11]. http://www.fda.gov/Drugs/DrugSafety/ucm245852.htm.
106. FDA Drug Safety Communication (28 February 2012): Safety label changes to cholesterol-lowering statin drugs. <>; [accessed 29.02.12]. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm.
107. Product label for Zocor (simvastatin). (Approved 06 October 2011). <>; [accessed 19.10.11]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019766s0831bl.p df.
108. Russo M.W., Scobey M., Bonkovsky H.L. Drug-induced liver injury associated with statins. Semin Liver Dis 2009, 29:412-422.
109. Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 2005, 41:690-695.
110. Bhardwaj S.S., Chalasani N. Lipid lowering agents that cause drug-induced hepatotoxicity. Clin Liver Dis 2007, 11:597-613.
111. Navarro V.J. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009, 29:373-382.
112. Dietary Supplement Health and Education Act of 1994 (DSHEA): FDA role. <>; [accessed 20.08.11]. http://www.fda.gov/food/dietarysupplements/default.htm.
113. Uetrecht J. Immunoallergic drug-induced liver injury in humans. Semin Liver Dis 2009, 29:383-392.
114. Tobon G.J., Cañas C., Jaller J.J., Restrepo J.C., Anaya J.M. Serious liver disease induced by infliximab. Clin Rheumatol 2007, 26:578-581.
115. Mancini S., Amorotti D., Vecchio S., Ponz de Leon M., Roncucci L. Infliximab-related hepatitis: discussion of a case and review of the literature. Intern Emerg Med 2010, 5:193-200.
116. Bezabeh S., Flowers C.M., Kortepeter C., Avigan M. Clinically significant liver injury in patients treated with natalizumab. Aliment Pharmacol Ther 2010, 31:1028-1035.
117. Duchini A. Autoimmune hepatitis and interferon beta-1a for multiple sclerosis. Am J Gastroenterol 2002, 97:767-768.
118. Esteve M., Saro C., González-Huix F., Suarez F., Forné M., Viver J.M. Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut 2004, 53:1363-1365.