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Current Drug Safety


ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Review Article

Idiosyncratic Drug-Induced Acute Liver Failure: A Challenging and Distressing Scenario

Author(s): Carla Stefania Colaci, Manuel Mendizabal and Fernando Bessone*

Volume 14, Issue 2, 2019

Page: [94 - 101] Pages: 8

DOI: 10.2174/1574886314666190215115434

Price: $65


Background: Idiosyncratic Drug Induced Liver Injury (DILI) is a rare adverse event to drugs that occasionally leads to severe liver damage, being one of the leading causes of Acute Liver Failure (ALF) in developed countries. DILI is largely a diagnosis of exclusion.

Discussion and Conclusion: Careful history of drug taking and ruling out other competing etiologies is mandatory given that DILI can present with an extremely variable phenotype. Several prognostic scores have been developed to promptly identify patients with potential risk of developing ALF. New biomarkers to diagnose and predict DILI evolution are under study and hopefully we will benefit from these novel tools in the near future.

Keywords: Hepatotoxicity, acute liver failure, liver transplant, drug hepatotoxicity, Drug-induced liver injury, hepatitis.

Graphical Abstract
Reuben A, Tillman H, Fontana RJ, et al. Outcomes in adults with acute liver failure between 1998 and 2013. Ann Intern Med 2016; 164(11): 724-32.
Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144(7): 1419-25.
Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug‐induced liver injury. Clin Pharmacol Ther 2011; 89(6): 806-15.
Fontana RJ. Acute liver failure due to drugs. Semin Liver Dis 2008; 28(2): 175-87.
Mendizabal M, Marciano S, Videla MG, et al. Changing etiologies and outcomes of acute liver failure: Perspectives from 6 transplant centers in Argentina. Liver Transpl 2014; 20(4): 483-9.
Goldberg DS, Forde KA, Carbonari DM, et al. Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system. Gastroenterology 2015; 148(7): 1353-61.
Bessone F, Nelia H, Sanchez-Ciceron A, et al. A comparative analysis of the Spanish and Latin-American prospective druginduced liver injury (DILI) networks. Hepatology 2015; 62: 504.
Hernández N, Bessone F, Sánchez A, et al. Profile of idiosyncratic drug induced liver injury in Latin America: An analysis of published reports. Ann Hepatol 2014; 13(2): 231-9.
Bessone F, Colombato L, Fassio E, Reggiardo MV, Vorobioff J, Tanno H. The spectrum of nimesulide-induced-hepatotoxicity: An overview. Antiinflamm Antiallergy Agents Med Chem 2010; 9(4): 355-65.
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): 950-66.
Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology 2015; 148(7): 1340-52.
Bessone F, Hernandez N, Mendizabal M, et al. When the creation of a consortium provides useful answers: Experience from the Latin-American DILI registry. Clin Liver Dis 2019; 13: 51-7.
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 2016; 36(2): 302-10.
Senior JR. Alanine aminotransferase: A clinical and regulatory tool for detecting liver injury-past, present, and future. Clin Pharmacol Ther 2012; 92(3): 332-9.
Danan G, Teschke R. RUCAM in drug and herb induced liver injury: The update. Int J Mol Sci 2015; 17(1): pii E14.
Benichou C, Danan G, Flahault A. Causality assessment of adverse reactions to drugs. An original model for validation of drug causality assessment methods: Case reports with positive rechallenge. J Clin Epidemiol 1993; 46(11): 1331-6.
Reuben A, Koch DG, Lee WM. Drug‐induced acute liver failure: Results of a US multicenter, prospective study. Hepatology 2010; 52(6): 2065-76.
Davern TJ, Chalasani N, Fontana RJ, et al. Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology 2011; 141(5): 1665-72.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018; 68(6): 1256-71.
Björnsson E, Talwalkar J, Treeprasertsuk S, et al. Drug‐induced autoimmune hepatitis: Clinical characteristics and prognosis. Hepatology 2010; 51(6): 2040-8.
Roberts EA, Schilsky ML. American Association for the study of the Liver Disease. Diagnosis and treatment of Wilson disease: An update. Hepatology 2008; 47(6): 2089-111.
Korman JD, Volenberg I, Balko J, et al. Screening for Wilson disease in acute liver failure: A comparison of currently available diagnostic tests. Hepatology 2008; 48(4): 1167-74.
Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the study of liver diseases position paper on acute liver failure 2011. Hepatology 2012; 55(3): 965-7.
Stravitz RT, Lefkowitch JH, Fontana RJ, et al. Autoimmune acute liver failure: Proposed clinical and histological criteria. Hepatology 2011; 53(2): 517-26.
Mendizabal M, Marciano S, Videla MG, et al. Fulminant presentation of autoimmune hepatitis: Clinical features and early predictors of corticosteroid treatment failure. Eur J Gastroenterol Hepatol 2015; 27(6): 644-8.
Flamm SL, Yang YX, Singh S, Falck-Ytter YT. AGA American Gastroenterological Association Institute guidelines for the diagnosis and management of acute liver failure. Gastroenterology 2017; 152(3): 644-7.
Herrine SK, Moayyedi P, Brown RS, Falck-Ytter YT. American Gastroenterological Association Institute technical review on initial testing and management of acute liver disease. Gastroenterology 2017; 125(3): 648-64.
Kleiner DE, Chalasani NO, Lee WM, et al. The use of liver biopsy evaluation in discrimination of idiopathic autoinmune hepatitis versus drug induced liver injury. Hepatology (Baltimore, Md) 2013; 54(3): 931-9.
Robles–Diaz M, Lucena MI, Kaplowitz N, et al. Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology 2014; 147(1): 109-18.
Hayashi PH, Rockey DC, Fontana RJ, et al. Death and liver transplantation within 2 years of onset of drug‐induced liver injury. Hepatology 2017; 66(4): 1275-85.
Tujios SR, Lee WM. Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy. Liver Int 2018; 38(1): 6-14.
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): 856-64.
European Association for the Study of the Liver, Clinical practice guidelines panel, Wendon J, et al.. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017; 66(5): 1047-81.
Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 2016; 64: 69-78.
Reddy KR, Ellerbe C, Schilsky M, et al. Determinants of outcome among patients with acute liver failure listed for liver transplantation in the United States. Liver Transpl 2016; 22(4): 505-15.
Habib S, Shaikh OS. Drug- induced acute liver failure. Clin Liver Dis 2017; 21(1): 151-62.
Robles-Díaz M, Medina-Caliz I, Stephens C, et al. Biomarkers in DILI: One more step forward. Front Pharmacol 2016; 7: 267.
Bessone F. Predicting fatalities in serious idiosyncratic drug-induced liver injury- a matter of choosing the best Hy’s law. Transl Gastroenterol Hepatol 2017; 2: 112.
Church RJ, Kullak‐Ublick GA, Aubrecht J, et al. Candidate biomarkers for the diagnosis and prognosis of drug‐induced liver injury: An international collaborative effort. Hepatology 2019; 69(2): 760-73.

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