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Current Hepatology Reports
Published in: Current Hepatology Reports 3/2018

01-09-2018 | Drug-Induced Liver Injury (NP Chalasani and MS Ghabril, Section Editors)

Long-Term Outcomes After Drug-Induced Liver Injury

Authors: Paul H. Hayashi, Einar S. Bjornsson

Published in: Current Hepatology Reports | Issue 3/2018

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Abstract

Purpose of the Review

This review serves to update the reader on emerging data regarding a spectrum of drug-induced liver injury (DILI) outcomes that lie between complete resolution and acute liver failure. Such outcomes can range from mild chronic injury to late liver failure and mortality.

Recent Findings

Several large registries are maturing with large numbers of DILI cases thus shedding light on outcomes including chronic injury and late fatality. We cover definitions commonly used to describe resolution versus chronic injury and mortality due to DILI. We look at rates of occurrence for these different outcomes in major registries. Three specific types of chronic DILI that are illustrative but also easily missed by clinicians are also described.

Summary

A small but important proportion of DILI cases do not resolve, going on to develop chronic injury and even liver failure. Defining and recognizing these cases is a challenge because DILI is rare, and chronic injury rarer still. Large registries are beginning to define these previously overlooked long-term outcomes.
Literature
1.
Reuben A, Tillman H, Fontana RJ, Davern T, McGuire B, Stravitz RT, et al. Outcomes in adults with acute liver failure between 1998 and 2013: an observational cohort study. Ann Intern Med. 2016;164(11):724–32.CrossRef
2.
• Bjornsson E, Davidsdottir L. The long-term follow-up after idiosyncratic drug-induced liver injury with jaundice. J Hepatol. 2009;50(3):511–7. Reports rate of chronic DILI in national (Sweden) hospital database. CrossRef
3.
Andrade RJ, Lucena MI, Fernandez MC, Pelaez G, Pachkoria K, Garcia-Ruiz E, 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):512–21.CrossRef
4.
Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924–1934.e4.CrossRef
5.
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.CrossRef
6.
European Association for the Study of the Liver. Electronic address eee, Clinical practice guidelines panel, Wendon J, Panel M, Cordoba J, Dhawan A, et al. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66(5):1047–81.CrossRef
7.
Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Gines P, et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol. 2014;61(5):1038–47.CrossRef
8.
Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, et al. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology. 2015;62(1):243–52.CrossRef
9.
Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology. 2012;55(2):447–54.CrossRef
10.
Aithal PG, Day CP. The natural history of histologically proved drug induced liver disease. Gut. 1999;44(5):731–5.CrossRef
11.
Toghill PJ, Smith PG, Benton P, Brown RC, Matthews HL. Methyldopa liver damage. Br Med J. 1974;3(5930):545–8.CrossRef
12.
Goldstein GB, Lam KC, Mistilis SP. Drug-induced active chronic hepatitis. Am J Dig Dis. 1973;18(3):177–84.CrossRef
13.
Seeff LB. Drug-induced chronic liver disease, with emphasis on chronic active hepatitis. Semin Liver Dis. 1981;1(2):104–15.CrossRef
14.
• Andrade RJ, Lucena MI, Kaplowitz N, Garcia-Munoz B, Borraz Y, Pachkoria K, et al. Outcome of acute idiosyncratic drug-induced liver injury: long-term follow-up in a hepatotoxicity registry. Hepatology. 2006;44(6):1581–8. Reports rate of chronic DILI in a registry accruing cases across Spain. CrossRef
15.
Fontana RJ, Hayashi PH, Gu J, Reddy KR, Barnhart H, Watkins PB, et al. Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology. 2014;147(1):96–108.e4.CrossRef
16.
•• Fontana RJ, Hayashi PH, Barnhart H, Kleiner DE, Reddy KR, Chalasani N, et al. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol. 2015;110(10):1450–9. Reports rate of chronic DILI at 12 months with quality of life data in a U.S. DILI registry. CrossRef
17.
• Bjornsson ES, Bergmann OM, Bjornsson 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. e1–3; quiz e19–20. Only population based study reporting DILI incidence and covering an entire nation (Iceland). CrossRef
18.
Zimmerman HJ. Drug-induce liver injury. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed Philadelphia: Lipponcott Williams & Wilkins. 1999:432–3.
19.
Farrell GC. Drug-induced chronic active hepatitis. In, Farrell GC. Drug-induced liver disease. Churchill Livingstone. 1994:423–38.
20.
Zimmerman HJ. Oncotherapeutic and immunosuppressive agents. In: Zimmerman HJ, editor. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lipponcott Williams & Wilkins; 1999. p. 681–7.
21.
Langman G, Hall PM, Todd G. Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol. 2001;16(12):1395–401.CrossRef
22.
Saphner T, Triest-Robertson S, Li H, Holzman P. The association of nonalcoholic steatohepatitis and tamoxifen in patients with breast cancer. Cancer. 2009;115(14):3189–95.CrossRef
23.
Mattar W, Juliar B, Gradus-Pizlo I, Kwo PY. Amiodarone hepatotoxicity in the context of the metabolic syndrome and right-sided heart failure. J Gastrointestin Liver Dis. 2009;18(4):419–23.PubMed
24.
deLemos AS, Foureau DM, Jacobs C, Ahrens W, Russo MW, Bonkovsky HL. Drug-induced liver injury with autoimmune features. Semin Liver Dis. 2014;34(2):194–204.CrossRef
25.
Amacher DE, Chalasani N. Drug-induced hepatic steatosis. Semin Liver Dis. 2014;34(2):205–14.CrossRef
26.
Reshamwala PA, Kleiner DE, Heller T. Nodular regenerative hyperplasia: not all nodules are created equal. Hepatology. 2006;44(1):7–14.CrossRef
27.
Ghabril M, Vuppalanchi R. Drug-induced nodular regenerative hyperplasia. Semin Liver Dis. 2014;34(2):240–5.CrossRef
28.
Carman N, Mack DR, Benchimol EI. Therapeutic drug monitoring in pediatric inflammatory bowel disease. Curr Gastroenterol Rep. 2018;20(5):18.CrossRef
29.
Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51(6):2193–213.CrossRef
30.
Angitapalli R, Litwin AM, Kumar PR, Nasser E, Lombardo J, Mashtare T, et al. Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer. Oncology. 2009;76(5):363–8.CrossRef
31.
Slade JH, Alattar ML, Fogelman DR, Overman MJ, Agarwal A, Maru DM, et al. Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury. Clin Colorectal Cancer. 2009;8(4):225–30.CrossRef
32.
Degott C, Feldmann G, Larrey D, Durand-Schneider AM, Grange D, Machayekhi JP, et al. Drug-induced prolonged cholestasis in adults: a histological semiquantitative study demonstrating progressive ductopenia. Hepatology. 1992;15(2):244–51.CrossRef
33.
Moradpour D, Altorfer J, Flury R, Greminger P, Meyenberger C, Jost R, et al. Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis. Hepatology. 1994;20(6):1437–41.CrossRef
34.
Olsson R, Wiholm BE, Sand C, Zettergren L, Hultcrantz R, Myrhed M. Liver damage from flucloxacillin, cloxacillin and dicloxacillin. J Hepatol. 1992;15(1–2):154–61.CrossRef
35.
•• Bonkovsky HL, Kleiner DE, Gu J, Odin JA, Russo MW, Navarro VM, et al. Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology. 2017;65(4):1267–77. Large report of DILI induced vanishing bile duct syndrome and poor outcomes. CrossRef
36.
Watanabe N, Takashimizu S, Kojima S, Kagawa T, Nishizaki Y, Mine T, et al. Clinical and pathological features of a prolonged type of acute intrahepatic cholestasis. Hepatol Res. 2007;37(8):598–607.CrossRef
37.
Chatterjee S, Richert L, Augustijns P, Annaert P. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis. Toxicol Appl Pharmacol. 2014;274(1):124–36.CrossRef
38.
Bachour-El Azzi P, Sharanek A, Abdel-Razzak Z, Antherieu S, Al-Attrache H, Savary CC, et al. Impact of inflammation on chlorpromazine-induced cytotoxicity and cholestatic features in HepaRG cells. Drug Metab Dispos. 2014;42(9):1556–66.CrossRef
39.
Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340–52. e7CrossRef
40.
Turkish A, Luo JJ, Lefkowitch JH. Ketamine abuse, biliary tract disease, and secondary sclerosing cholangitis. Hepatology. 2013;58(2):825–7.CrossRef
41.
•• Gudnason HO, Bjornsson HK, Gardarsdottir M, Thorisson HM, Olafsson S, Bergmann OM, et al. Secondary sclerosing cholangitis in patients with drug-induced liver injury. Dig Liver Dis. 2015;47(6):502–7. Series of DILI induced sclerosing cholangitis reported from an Icelandic DILI registry. CrossRef
42.
Horsley-Silva JL, Dow EN, Menias CO, Smith ML, Carballido EM, Lindor KD, et al. Docetaxel induced sclerosing cholangitis. Dig Dis Sci. 2015;60(12):3814–6.CrossRef
43.
•• Ahmad J, Rossi S, Rodgers SK, Ghabril M, Fontana R, Stolz A, et al. Sclerosing cholangitis like changes on magnetic resonance cholangiography in patients with drug induced liver injury. Clin Gastroenterol Hepatol (in press). Series of DILI induced sclerosing cholangitis reported from a U.S. DILI registry with blinded and systematic MRCP readings.
44.
Gossard AA, Angulo P, Lindor KD. Secondary sclerosing cholangitis: a comparison to primary sclerosing cholangitis. Am J Gastroenterol. 2005;100(6):1330–3.CrossRef
45.
Imam MH, Talwalkar JA, Lindor KD. Secondary sclerosing cholangitis: pathogenesis, diagnosis, and management. Clin Liver Dis. 2013;17(2):269–77.CrossRef
46.
Dikengil A, Siskind BN, Morse SS, Swedlund A, Bober-Sorcinelli KE, Burrell MI. Sclerosing cholangitis from intraarterial floxuridine. J Clin Gastroenterol. 1986;8(6):690–3.CrossRef
47.
Ludwig J, Kim CH, Wiesner RH, Krom RA. Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy? Hepatology. 1989;9(2):215–8.CrossRef
48.
Schwab GP, Wetscher GJ, Vogl W, Redmond E. Methimazole-induced cholestatic liver injury, mimicking sclerosing cholangitis. Langenbecks Arch Chir. 1996;381(4):225–7.CrossRef
49.
Seto WK, Ng M, Chan P, Ng IO, Cheung SC, Hung IF, et al. Ketamine-induced cholangiopathy: a case report. Am J Gastroenterol. 2011;106(5):1004–5.CrossRef
50.
Bjornsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology. 2005;42(2):481–9.CrossRef
51.
Hayashi PH, Fontana RJ. Clinical features, diagnosis, and natural history of drug-induced liver injury. Semin Liver Dis. 2014;34(2):134–44.CrossRef
52.
•• Hayashi PH, Rockey DC, Fontana RJ, Tillmann HL, Kaplowitz N, Barnhart HX, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66(4):1275–85. Report of long-term mortality from DILI in prospectively followed patients. CrossRef
Metadata
Title
Long-Term Outcomes After Drug-Induced Liver Injury
Authors
Paul H. Hayashi
Einar S. Bjornsson
Publication date
01-09-2018
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 3/2018
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-018-0411-0

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