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Review

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review

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Pages 517-536 | Received 16 Sep 2015, Accepted 01 Dec 2015, Published online: 25 Dec 2015

References

  • Lewis JH. The art and science of diagnosing and managing drug-induced liver injury in 2015 and beyond. Clin Gastroenterol Hepatol. 2015;13(12):2173–2189.e8.
  • Marino G, Zimmerman HJ, Lewis JH. Management of drug-induced liver disease. Curr Gastroenterol Rep. 2001;3(1):38–48.
  • Lewis JH. Drug-induced liver injury throughout the drug development life cycle: where we have been, where we are now, and where we are headed. Perspectives of a clinical hepatologist. Pharm Med. 2013;27:165–191.
  • Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950–966; quiz 967.
  • Saliba F, Samuel D. Artificial liver support: a real step forward. Minerva Med. 2015;106(1):35–43.
  • Senior JR. How can ‘Hy’s law’ help the clinician? Pharmacoepidemiol Drug Saf. 2006;15(4):235–239.
  • Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065–2076.
  • Aithal GP. Pharmacogenetic testing in idiosyncratic drug-induced liver injury: current role in clinical practice. Liver Int. 2015;35(7):1801–1808.
  • Matsumoto T, Ohno M, Azuma J. Future of pharmacogenetics-based therapy for tuberculosis. Pharmacogenomics. 2014;15(5):601–607.
  • Gunnell D, Hawton K, Murray V, et al. Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are restrictions on availability justified? J Epidemiol Community Health. 1997;51(2):175–179.
  • Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther. 2013;37(12):1132–1156.
  • Devarbhavi H, Singh R, Patil M, et al. Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury. J Gastroenterol Hepatol. 2013;28(1):161–167.
  • Hawkins MT, Lewis JH. Latest advances in predicting DILI in human subjects: focus on biomarkers. Expert Opin Drug Metab Toxicol. 2012;8(12):1521–1530.
  • Senior JR. New biomarkers for drug-induced liver injury: are they really better? What do they diagnose? Liver Int. 2014;34(3):325–327.
  • Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174(8):935–952.
  • Hayashi PH, Fontana RJ, Chalasani NP, et al. Under-reporting and poor adherence to monitoring guidelines for severe cases of isoniazid hepatotoxicity. Clin Gastroenterol Hepatol. 2015;13(9):1676–1682.e1671.
  • Hoofnagle JH, Serrano J, Knoben JE, et al. LiverTox: a website on drug-induced liver injury. Hepatology. 2013;57(3):873–874.
  • Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. Philadelphia (PA): Lippincott-Williams & Wilkins; 1999.
  • Nikolaos P. Drug hepatotoxicity. Clin Liver Dis. 2013;17(4):507–786.
  • Kaplowitz N, DeLeve LD, editors. Drug-induced liver disease. 3rd ed. London: Elsevier/Academic Press; 2013. p. 746 p.
  • Rockey DC, Seeff LB, Rochon J, 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(6):2117–2126.
  • Shapiro MA, Lewis JH. Causality assessment of drug-induced hepatotoxicity: promises and pitfalls. Clin Liver Dis. 2007;11(3):477–505, v.
  • Garcia-Cortes M, Stephens C, Lucena MI, et al. Causality assessment methods in drug induced liver injury: strengths and weaknesses. J Hepatol. 2011;55(3):683–691.
  • Aithal GP, Rawlins MD, Day CP. Accuracy of hepatic adverse drug reaction reporting in one English health region. Bmj. 1999;319(7224):1541.
  • Regev A, Seeff LB, Merz M, et al. Causality assessment for suspected DILI during clinical phases of drug development. Drug Safety. 2014;37(Suppl 1):S47–S56.
  • Avigan MI, Bjornsson ES, Pasanen M, et al. Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials. Drug Safety. 2014;37(Suppl 1):S19–S31.
  • Agarwal VK, McHutchison JG, Hoofnagle JH. Important elements for the diagnosis of drug-induced liver injury. Clin Gastroenterol Hepatol. 2010;8(5):463–470.
  • Lewis JH. The adaptive response (drug tolerance) helps to prevent drug-induced liver injury. Gastroenterol Hepatol. 2012;8(5):333–336.
  • FDA Drug Guidance. http://www.fda.gov/downloads/Drugs/…/Guidances/UCM174090.pdf
  • Temple R. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15(4):241–243.
  • Kaplowitz N. Rules and laws of drug hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15(4):231–233.
  • Lewis JH. ‘Hy’s law,’ the ‘Rezulin Rule,’ and other predictors of severe drug-induced hepatotoxicity: putting risk-benefit into perspective. Pharmacoepidemiol Drug Saf. 2006;15(4):221–229.
  • Andrade RJ, Lucena MI, 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.
  • Senior JR. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges. Drug Safety. 2014;37(Suppl 1):S9–17.
  • Papay JI, Clines D, Rafi R, et al. Drug-induced liver injury following positive drug rechallenge. Regul Toxicol Pharmacol. 2009;54(1):84–90.
  • Hunt CM, Papay JI, Rich DS, et al. The evaluation of drug rechallenge: the casopitant Phase III program. Regul Toxicol Pharmacol. 2010;58(3):539–543.
  • Sharma SK, Singla R, Sarda P, et al. Safety of 3 different reintroduction regimens of antituberculosis drugs after development of antituberculosis treatment-induced hepatotoxicity. Clin Infect Dis. 2010;50(6):833–839.
  • Saukkonen J. Challenges in reintroducing tuberculosis medications after hepatotoxicity. Clin Infect Dis. 2010;50(6):840–842.
  • Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the attractive hazard. Expert Opin Drug Saf. 2009;8(6):709–714.
  • Thongraung W, Lertphongpiroon W, Pungrassami P, et al. Physicians’ practices regarding management of antituberculosis drug-induced hepatotoxicity. Southeast Asian J Trop Med Public Health. 2012;43(3):724–734.
  • Senousy BE, Belal SI, Draganov PV. Hepatotoxic effects of therapies for tuberculosis. Nat Rev Gastroenterol Hepatol. 2010;7(10):543–556.
  • Lebovitz HE. Differentiating members of the thiazolidinedione class: a focus on safety. Diabetes Metab Res Rev. 2002;18(Suppl 2):S23–S29.
  • Charles EC, Olson KL, Sandhoff BG, et al. Evaluation of cases of severe statin-related transaminitis within a large health maintenance organization. Am J Med. 2005;118(6):618–624.
  • Anastasia EJ, Rosenstein RS, Bergsman JA, et al. Use of apixaban after development of suspected rivaroxaban-induced hepatic steatosis; a case report. Blood Coagul Fibrinolysis. 2015;26(6):699–702.
  • Stine JG, Lewis JH. Hepatotoxicity of antibiotics: a review and update for the clinician. Clin Liver Dis. 2013;17(4):609–642, ix.
  • Brinker AD, Wassel RT, Lyndly J, et al. Telithromycin-associated hepatotoxicity: clinical spectrum and causality assessment of 42 cases. Hepatology. 2009;49(1):250–257.
  • Dart RC, Erdman AR, Olson KR, et al. Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Philadelphia, PA). 2006;44(1):1–18.
  • Ahishali E, Boynuegri B, Ozpolat E, et al. Approach to mushroom intoxication and treatment: can we decrease mortality? Clin Res Hepatol Gastroenterol. 2012;36(2):139–145.
  • Colak S, Kandis H, Afacan MA, et al. Assessment of patients who presented to the emergency department with mushroom poisoning. Hum Exp Toxicol. 2015;34(7):725–731.
  • Chyka PA, Erdman AR, Christianson G, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Philadelphia, PA). 2007;45(2):95–131.
  • Isbister GK, Kumar VV. Indications for single-dose activated charcoal administration in acute overdose. Curr Opin Crit Care. 2011;17(4):351–357.
  • McNamara RM, Aaron CK, Gemborys M, et al. Efficacy of charcoal cathartic versus ipecac in reducing serum acetaminophen in a simulated overdose. Ann Emerg Med. 1989;18(9):934–938.
  • Saincher A, Sitar DS, Tenenbein M. Efficacy of ipecac during the first hour after drug ingestion in human volunteers. J Toxicol Clin Toxicol. 1997;35(6):609–615.
  • Christophersen AB, Levin D, Hoegberg LC, et al. Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication. Br J Clin Pharmacol. 2002;53(3):312–317.
  • Tenenbein PK, Sitar DS, Tenenbein M. Interaction between N-acetylcysteine and activated charcoal: implications for the treatment of acetaminophen poisoning. Pharmacotherapy. 2001;21(11):1331–1336.
  • Farrell SEDG, Tarabar A et al. Acetaminophen toxicity treatment & management. http://emedicine.medscape.com/article/820200-treatment#d12
  • Wolf SJ, Heard K, Sloan EP, et al. Clinical policy: critical issues in the management of patients presenting to the emergency department with acetaminophen overdose. Ann Emerg Med. 2007;50(3):292–313.
  • Buckley NA, Whyte IM, O’Connell DL, et al. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. J Toxicol Clin Toxicol. 1999;37(6):753–757.
  • Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health. 2010;7(7):2745–2788.
  • Blanusa M, Varnai VM, Piasek M, et al. Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771–2794.
  • Aaseth J, Skaug MA, Cao Y, et al. Chelation in metal intoxication–principles and paradigms. J Trace Elem Med Biol. 2015;31:260–266.
  • Cappellini MD, Pattoneri P. Oral iron chelators. Annu Rev Med. 2009;60:25–38.
  • Xia S, Zhang W, Huang L, et al. Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials. PLoS One. 2013;8(12):e82662.
  • Green JL, Heard KJ, Reynolds KM, et al. Oral and intravenous acetylcysteine for treatment of acetaminophen toxicity: a systematic review and meta-analysis. West J Emerg Med. 2013;14(3):218–226.
  • Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol. 2002;40(1):3–20.
  • Mitchell JR, Jollow DJ, Potter WZ, et al. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther. 1973;187(1):185–194.
  • Daly FF, Fountain JS, Murray L, et al. Guidelines for the management of paracetamol poisoning in Australia and New Zealand–explanation and elaboration. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. Med J Aust. 2008;188(5):296–301.
  • Bunchorntavakul C, Reddy KR. Acetaminophen-related hepatotoxicity. Clin Liver Dis. 2013;17(4):587–607, viii.
  • Smilkstein MJ, Knapp GL, Kulig KW, et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988;319(24):1557–1562.
  • Chan ST, Chan CK, Tse ML. Paracetamol overdose in Hong Kong: is the 150-treatment line good enough to cover patients with paracetamol-induced liver injury? Hong Kong Med J. 2015;21(5):389–393.
  • Bateman DN, Dear JW, Carroll R, et al. Impact of reducing the threshold for acetylcysteine treatment in acute paracetamol poisoning: the recent United Kingdom experience. Clin Toxicol (Philadelphia, PA). 2014;52(8):868–872.
  • Bari KFR. Acetaminophen overdose: what practitioners need to know. AASLD Clin Liver Dis. 2014;4(1):17–21.
  • Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet. 2014;383(9918):697–704.
  • Bebarta VS, Kao L, Froberg B, et al. A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose. Clin Toxicol (Philadelphia, PA). 2010;48(5):424–430.
  • Schmidt LE. Identification of patients at risk of anaphylactoid reactions to N-acetylcysteine in the treatment of paracetamol overdose. Clin Toxicol (Philadelphia, PA). 2013;51(6):467–472.
  • Waring WS, Stephen AF, Robinson OD, et al. Lower incidence of anaphylactoid reactions to N-acetylcysteine in patients with high acetaminophen concentrations after overdose. Clin Toxicol (Philadelphia, PA). 2008;46(6):496–500.
  • Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Philadelphia, PA). 2009;47(2):81–88.
  • Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med. 1998;31(6):710–715.
  • Baniasadi S, Eftekhari P, Tabarsi P, et al. Protective effect of N-acetylcysteine on antituberculosis drug-induced hepatotoxicity. Eur J Gastroenterol Hepatol. 2010;22(10):1235–1238.
  • Khandelwal N, James LP, Sanders C, et al. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. Hepatology. 2011;53(2):567–576.
  • Singh S, Hynan LS, Lee WM. Improvements in hepatic serological biomarkers are associated with clinical benefit of intravenous N-acetylcysteine in early stage non-acetaminophen acute liver failure. Dig Dis Sci. 2013;58(5):1397–1402.
  • Hu J, Zhang Q, Ren X, et al. Efficacy and safety of acetylcysteine in “non-acetaminophen” acute liver failure: a meta-analysis of prospective clinical trials. Clin Res Hepatol Gastroenterol. 2015;39(5):594–599.
  • Sundaram V, Shaikh OS. Acute liver failure: current practice and recent advances. Gastroenterol Clin North Am. 2011;40(3):523–539.
  • Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856–864, 864.e851.
  • Squires RH, Dhawan A, Alonso E, et al. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial. Hepatology. 2013;57(4):1542–1549.
  • Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management. Drug Safety. 1999;21(6):489–501.
  • Avancini J, Maragno L, Santi CG, et al. Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome: clinical features of 27 patients. Clin Exp Dermatol. 2015;40(8):851–859.
  • Lee T, Lee YS, Yoon SY, et al. Characteristics of liver injury in drug-induced systemic hypersensitivity reactions. J Am Acad Dermatol. 2013;69(3):407–415.
  • Teo YL, Ho HK, Chan A. Formation of reactive metabolites and management of tyrosine kinase inhibitor-induced hepatotoxicity: a literature review. Expert Opin Drug Metab Toxicol. 2015;11(2):231–242.
  • Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Safety. 2013;36(7):491–503.
  • Valle JW, Faivre S, Hubner RA, et al. Practical management of sunitinib toxicities in the treatment of pancreatic neuroendocrine tumors. Cancer Treat Rev. 2014;40(10):1230–1238.
  • Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723.
  • Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):2691–2697.
  • Ahmed T, Pandey R, Shah B, et al. Resolution of ipilimumab induced severe hepatotoxicity with triple immunosuppressants therapy. BMJ Case Rep. 2015. DOI:10.1136/bcr-2014-208102.
  • Cheng R, Cooper A, Kench J, et al. Ipilimumab-induced toxicities and the gastroenterologist. J Gastroenterol Hepatol. 2015;30(4):657–666.
  • Alla V, Abraham J, Siddiqui J, et al. Autoimmune hepatitis triggered by statins. J Clin Gastroenterol. 2006;40(8):757–761.
  • Prussick R, Shear NH. Dapsone hypersensitivity syndrome. J Am Acad Dermatol. 1996;35(2 Pt 2):346–349.
  • Lee WM, Denton WT. Chronic hepatitis and indolent cirrhosis due to methyldopa: the bottom of the iceberg? J S C Med Assoc. 1989;85(2):75–79.
  • Russo MW, Hoofnagle JH, Gu J, et al. Spectrum of statin hepatotoxicity: experience of the drug-induced liver injury network. Hepatology. 2014;60(2):679–686.
  • Bjornsson E, Talwalkar J, Treeprasertsuk S, et al. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010;51(6):2040–2048.
  • Stine JG, Chalasani N. Chronic liver injury induced by drugs: a systematic review. Liver Int. 2015;35(11):2343–2353.
  • Czaja AJ. Drug-induced autoimmune-like hepatitis. Dig Dis Sci. 2011;56(4):958–976.
  • Bessone F, Lucena MI, Roma MG, et al. Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases. Liver Int. 2015. [Epub ahead of print]
  • Adar T, Mizrahi M, Pappo O, et al. Adalimumab-induced autoimmune hepatitis. J Clin Gastroenterol. 2010;44(1):e20–e22.
  • Aliberti S, Grignani G, Allione P, et al. An acute hepatitis resembling autoimmune hepatitis occurring during imatinib therapy in a gastrointestinal stromal tumor patient. Am J Clin Oncol. 2009;32(6):640–641.
  • Bilgi N, Bell K, Ananthakrishnan AN, et al. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother. 2010;44(5):926–928.
  • Mancini S, Amorotti E, Vecchio S, et al. Infliximab-related hepatitis: discussion of a case and review of the literature. Intern Emerg Med. 2010;5(3):193–200.
  • Poulin Y, Therien G. Drug-induced hepatitis and lupus during infliximab treatment for psoriasis: case report and literature review. J Cutan Med Surg. 2010;14(2):100–104.
  • Prandota J. Important role of proinflammatory cytokines/other endogenous substances in drug-induced hepatotoxicity: depression of drug metabolism during infections/inflammation states, and genetic polymorphisms of drug-metabolizing enzymes/cytokines may markedly contribute to this pathology. Am J Ther. 2005;12(3):254–261.
  • Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 889 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–1352.
  • Andrade RJ, Lucena MI, Fernandez MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129(2):512–521.
  • Bjornsson E, Jerlstad P, Bergqvist A, et al. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005;40(9):1095–1101.
  • Mohi-ud-din R, Lewis JH. Drug- and chemical-induced cholestasis. Clin Liver Dis. 2004;8(1):95–132, vii.
  • O’Brien CB, Shields DS, Saul SH, et al. Drug-induced vanishing bile duct syndrome: response to ursodiol. Am J Gastroenterol. 1996;91(7):1456–1457.
  • Mork H, Al-Taie O, Klinge O, et al. [Successful therapy of persistent androgen-induced cholestasis with ursodeoxycholic acid]. Z Gastroenterol. 1997;35(12):1087–1091.
  • Katsinelos P, Vasiliadis T, Xiarchos P, et al. Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium (Augmentin)-induced intra-hepatic cholestasis: report of two cases. Eur J Gastroenterol Hepatol. 2000;12(3):365–368.
  • Uraz S, Tahan V, Aygun C, et al. Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity. Dig Dis Sci. 2008;53(4):1071–1077.
  • Wree A, Dechene A, Herzer K, et al. Steroid and ursodesoxycholic Acid combination therapy in severe drug-induced liver injury. Digestion. 2011;84(1):54–59.
  • Tani M, Hayashi Y, Okamoto S, et al. Rapid improvement of icterus and pruritus by the oral administration of colestimide in two cases of drug-induced hepatitis. Intern Med (Tokyo, Japan). 2001;40(11):1098–1103.
  • Wong SP, Chu CM, Kan CH, et al. Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy. J Clin Rheumatol. 2009;15(8):389–392.
  • Leflunomide Monograph for Professionals. http://www.drugs.com/monograph/leflunomide.html
  • Abenavoli L, Capasso R, Milic N, et al. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010;24(10):1423–1432.
  • Gu J, Tang SJ, Tan SY, et al. An open-label, randomized and multi-center clinical trial to evaluate the efficacy of Silibinin in preventing drug-induced liver injury. Int J Clin Exp Med. 2015;8(3):4320–4327.
  • Luangchosiri C, Thakkinstian A, Chitphuk S, et al. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015;15(1):334.
  • Thyagarajan SP, Jayaram S, Gopalakrishnan V, et al. Herbal medicines for liver diseases in India. J Gastroenterol Hepatol. 2002;17(Suppl 3):S370–S376.
  • Koga K, Kawashima S, Shibata N, et al. [Novel formulations of a liver protection drug glycyrrhizin]. Yakugaku Zasshi. 2007;127(7):1103–1114.
  • Wang GS, Han ZW. [The protective action of glycyrrhiza flavonoids against carbon tetrachloride hepatotoxicity in mice]. Yao Xue Xue Bao. 1993;28(8):572–576.
  • Papaseit E, Farre M, Lopez MJ, et al. A case of acute valproic acid poisoning treated successfully with L-carnitine. Eur J Emerg Med. 2012;19(1):57–58.
  • Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007;19(2):206–210.
  • Xiong H, Liu CT, Zhang YH, et al. [Valproic acid-induced idiosyncratic liver injury in 4 cases]. Zhonghua Er Ke Za Zhi Chin J Pediatr. 2012;50(12):890–894.
  • Shea B, Swinden MV, Ghogomu ET, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol. 2014;41(6):1049–1060.
  • Neuvonen PJ, Tokola O, Toivonen ML, et al. Methionine in paracetamol tablets, a tool to reduce paracetamol toxicity. Int J Clin Pharmacol Ther Toxicol. 1985;23(9):497–500.
  • Poirier LA. The role of methionine in carcinogenesis in vivo. Adv Exp Med Biol. 1986;206:269–282.
  • Jones AL, Hayes PC, Proudfoot AT, et al. Should methionine be added to every paracetamol tablet? Bmj. 1997;315(7103):301–304.
  • Yayla M, Halici Z, Unal B, et al. Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced acute liver toxicity in rats. Eur J Pharmacol. 2014;726:87–95.
  • Elshazly SM, El-Moselhy MA, Barakat W. Insights in the mechanism underlying the protective effect of alpha-lipoic acid against acetaminophen-hepatotoxicity. Eur J Pharmacol. 2014;726:116–123.
  • Banares R, Nevens F, Larsen FS, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2013;57(3):1153–1162.
  • Liu CT, Chen TH, Cheng CY. Successful treatment of drug-induced acute liver failure with high-volume plasma exchange. J Clin Apher. 2013;28(6):430–434.
  • Mindikoglu AL, Magder LS, Regev A. Outcome of liver transplantation for drug-induced acute liver failure in the United States: analysis of the United Network for Organ Sharing database. Liver Transpl. 2009;15(7):719–729.
  • Tillmann HL, Rockey DC. Improved prediction of the need for liver transplantation in patients with drug-induced liver injury? Gastroenterology. 2014;147(6):1441.
  • Gupta NK, Lewis JH. Review article: the use of potentially hepatotoxic drugs in patients with liver disease. Aliment Pharmacol Ther. 2008;28(9):1021–1041.
  • Kwon YS, Koh WJ, Suh GY, et al. Hepatitis C virus infection and hepatotoxicity during antituberculosis chemotherapy. Chest. 2007;131(3):803–808.
  • Sulkowski MS, Thomas DL, Mehta SH, et al. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology. 2002;35(1):182–189.
  • Lee SW, Park HJ, Kim BK, et al. Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate. Arthritis Res Ther. 2012;14(5):R232.
  • Watkins PB, Lewis JH, Kaplowitz N, et al. Clinical pattern of tolvaptan-associated liver injury in subjects with autosomal dominant polycystic kidney disease: analysis of clinical trials database. Drug Saf. 2015;38(11):1103–1113.
  • Gahr M, Kratzer W, Fuchs M, et al. Safety and tolerability of agomelatine: focus on hepatotoxicity. Curr Drug Metab. 2014;15(7):694–702.
  • Podcast: FDS. FDA limits usage of nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal glad problems. http://www.fda.gov/drugs/drugsafety/drugsafetypodcasts/ucm362820.htm
  • Mandell L, Tillotson G. Safety of fluoroquinolones: an update. Can J Infect Dis. 2002;13(1):54–61.
  • Telithromycin. (marketed as Ketek) information. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107824.htm
  • Delco F, Tchambaz L, Schlienger R, et al. Dose adjustment in patients with liver disease. Drug Safety. 2005;28(6):529–545.
  • Bjornsson ES, Jacobsen EI, Einarsdottir R, et al. Discrepancies in liver disease labeling in the package inserts of commonly prescribed medications. Gastroenterology. 2015;148(2):269–273.
  • Lucena MI, Andrade RJ, Tognoni G, et al. Drug use for non-hepatic associated conditions in patients with liver cirrhosis. Eur J Clin Pharmacol. 2003;59(1):71–76.
  • Benson GD, Koff RS, Tolman KG. The therapeutic use of acetaminophen in patients with liver disease. Am J Ther. 2005;12(2):133–141.
  • Rossi S, Assis DN, Awsare M, et al. Use of over-the-counter analgesics in patients with chronic liver disease: physicians’ recommendations. Drug Safety. 2008;31(3):261–270.
  • Nguyen DBN, Abdelaziz D, Lewis JH. Trainees’ attitudes and preferences towards the use of over the counter analgesics in patients with chronic liver disease. Adv Pharmacoepidemiol Drug Saf. 2014;3:167. DOI:10.4172/2167-1052.1000167.
  • Zimmerman HJ, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatology. 1995;22(3):767–773.
  • Lewis JH. Clinical perspective: statins and the liver–harmful or helpful? Dig Dis Sci. 2012;57(7):1754–1763.
  • Vuppalanchi R, Teal E, Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci. 2005;329(2):62–65.
  • 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(5):1453–1463.
  • Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci. 2014;59(8):1958–1965.
  • Lewis JH. Prescribing a statin to a cirrhotic patient to reduce hepatic decompensation and improve survival: impossible you say? Dig Dis Sci. 2014;59(8):1684–1687.
  • Singh S, Singh PP, Singh AG, et al. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology. 2013;144(2):323–332.
  • Suzuki Y, Tokimatsu I, Sato Y, et al. Association of sustained high plasma trough concentration of voriconazole with the incidence of hepatotoxicity. Clin Chim Acta. 2013;424:119–122.
  • Matsumoto K, Abematsu K, Shigemi A, et al. Therapeutic drug monitoring of voriconazole in Japanese patients: analysis based on clinical practice data. J Chemother (Florence, Italy). 2015;1973947815y0000000057. [Epub ahead of print]
  • Graham GG, Day RO, Graudins A, et al. FDA proposals to limit the hepatotoxicity of paracetamol (acetaminophen): are they reasonable? Inflammopharmacology. 2010;18(2):47–55.
  • Michna E, Duh MS, Korves C, et al. Removal of opioid/acetaminophen combination prescription pain medications: assessing the evidence for hepatotoxicity and consequences of removal of these medications. Pain Medicine (Malden, MA). 2010;11(3):369–378.
  • King JP, Davis TC, Bailey SC, et al. Developing consumer-centered, nonprescription drug labeling a study in acetaminophen. Am J Prev Med. 2011;40(6):593–598.
  • Hawton K, Bergen H, Simkin S, et al. Impact of different pack sizes of paracetamol in the United Kingdom and Ireland on intentional overdoses: a comparative study. BMC Public Health. 2011;11:460.
  • Hawton K, Bergen H, Simkin S, et al. Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses. Bmj. 2013;346:f403.
  • King JP, McCarthy DM, Serper M, et al. Variability in acetaminophen labeling practices: a missed opportunity to enhance patient safety. J Med Toxicol. 2015;11(4):410–414.
  • Civan JM, Navarro V, Herrine SK, et al. Patterns of acetaminophen use exceeding 4 grams daily in a hospitalized population at a tertiary care center. Gastroenterol Hepatol. 2014;10(1):27–34.
  • Lewis JH. Drug-induced liver disease. Med Clin North Am. 2000;84(5):1275–1311, x.
  • Graham DJ, Drinkard CR, Shatin D, et al. Liver enzyme monitoring in patients treated with troglitazone. Jama. 2001;286(7):831–833.
  • Watkins PB. Managing the risk of drug-induced liver injury. Clin Pharmacol Ther. 2013;94(6):629–631.
  • Blanchette CM, Nunes AP, Lin ND, et al. Adherence to risk evaluation and mitigation strategies (REMS) requirements for monthly testing of liver function. Drugs Context. 2015;4. pii: 212272.
  • Pollock NR, Colby D, Rolland JP. A point-of-care paper-based fingerstick transaminase test: toward low-cost “lab-on-a-chip” technology for the developing world. Clin Gastroenterol Hepatol. 2013;11(5):478–482.
  • Lee WM. Drug-induced acute liver failure. Clin Liver Dis. 2013;17(4):575–586, viii.
  • Phillips E, Mallal S. Successful translation of pharmacogenetics into the clinic: the abacavir example. Mol Diagn Ther. 2009;13(1):1–9.
  • Daly AK, Day CP. Genetic association studies in drug-induced liver injury. Drug Metab Rev. 2012;44(1):116–126.
  • Urban TJ, Daly AK, Aithal GP. Genetic basis of drug-induced liver injury: present and future. Semin Liver Dis. 2014;34(2):123–133.
  • Urban TJ, Shen Y, Stolz A, et al. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. Pharmacogenet Genomics. 2012;22(11):784–795.
  • Lee SW, Chung LS, Huang HH, et al. NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis drug-induced hepatitis. Int J Tuberc Lung Dis. 2010;14(5):622–626.
  • Tang SW, Lv XZ, Zhang Y, et al. CYP2E1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: a nested case-control study. J Clin Pharm Ther. 2012;37(5):588–593.
  • Bell LN, Vuppalanchi R, Watkins PB, et al. Serum proteomic profiling in patients with drug-induced liver injury. Aliment Pharmacol Ther. 2012;35(5):600–612.
  • Starkey Lewis PJ, Dear J, Platt V, et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology. 2011;54(5):1767–1776.
  • Roderburg C, Benz F, Vargas Cardenas D, et al. Elevated miR-122 serum levels are an independent marker of liver injury in inflammatory diseases. Liver Int. 2015;35(4):1172–1184.
  • Antoine DJ, Dear JW, Lewis PS, et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology. 2013;58(2):777–787.
  • Yang X, Salminen WF, Shi Q, et al. Potential of extracellular microRNAs as biomarkers of acetaminophen toxicity in children. Toxicol Appl Pharmacol. 2015;284(2):180–187.
  • Antoine DJ, Sabbisetti VS, Francis B, et al. Circulating kidney injury molecule 1 predicts prognosis and poor outcome in patients with acetaminophen-induced liver injury. Hepatology. 2015;62(2):591–599.
  • Momen-Heravi F, Bala S, Bukong T, et al. Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages. Nanomed Nanotechnol Biol Med. 2014;10(7):1517–1527.
  • Reddy LH, Couvreur P. Nanotechnology for therapy and imaging of liver diseases. J Hepatol. 2011;55:1461–1466.
  • Cui Y, Liu H, Ze Y, et al. Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice. Toxicol Sci. 2012;128(1):171–185.
  • Isoda K, Hasezaki T, Kondoh M, et al. Effect of surface charge on nano-sized silica particles-induced liver injury. Pharmazie. 2011;66(4):278–281.
  • Possamai LA, McPhail MJ, Khamri W, et al. The role of intestinal microbiota in murine models of acetaminophen-induced hepatotoxicity. Liver Int. 2015;35(3):764–773.
  • Goodsaid FMFF, Matters W. The predictive safety testing consortium: a synthesis of the goals, challenges and accomplishments of the Critical Path. Drug Disc Today Technol. 2007;4(2):47–50.
  • (iSAEC). The international serious adverse event consortium. www.saeconsortium.org
  • The DILI-sim initiative and DILIsym software. http://dilisym.com

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