hepatotoxicity
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Introduction
Toxic to the liver.
Etiology
- hepatotoxic pharmaceutical agents include:
- acetaminophen (paracetamol)* most common[3]
- allopurinol
- aminosalicylate
- amoxicillin/clavulanate (Augmentin)*
- chlorpromazine
- dapsone
- didanosine
- erythromycin estolate
- estrogens
- ethionamide
- glyburide
- halothane
- isoniazid
- ketoconazole
- methimazole
- methotrexate
- methoxyflurane
- methyldopa
- monoamine oxidase (MAO) inhibitors
- niacin (nicotinic acid)
- nifedipine
- nitrofurantoin
- phenytoin*
- propoxyphene
- propylthiouracil
- pyridium
- rifampin
- salicylates
- sulfonamides
- tamoxifen
- tetracyclines
- trimethoprim/sulfamethoxazole
- valproic acid (sodium valproate)*
- vitamin A
- zidovudine
- >= 10 events/10,000 person years
- 5-10 events/10,000 person years
Epidemiology
- single prescription medication in 73% of subjects
- dietary supplement in 9%
- more that 1 prescription medication (or a prescription plus a dietary supplement) in 18%
- most commonly implicated drug classes were antibiotics (46%) & central nervous system agents, i.e. antiseizure or psychotropic drugs (15%)
- most commonly implicated single agent was amoxicillin/clavulanate (23 cases)
- nitrofurantoin, isoniazid, & trimethoprim/sulfamethoxazole were implicated in 13 cases each
- as defined by specified patterns of serum ALT & serum ALP,
- 57% of cases hepatocellular
- 23% cholestatic
- 20% were mixed
- 69% of patients developed jaundice,
- 60% were hospitalized
- 8% died within 6 months[2]
Pathology
Complications
- hospitalization (59%)
- liver failure requiring liver transplantation (4.5%)
- acetaminophen overdose is most common cause[3]
- death (4.8%)
- persistent liver damage (19%)[6]
Differential diagnosis
- viral hepatitis, especially acute hepatitis C infection
Management
- remove offending agent
- N-acetylcysteine used to treat acute liver failure due to drug-induced liver injury (including drugs other than acetaminophen)
- treatment of drug induced hepatotoxicity in the absence of acute liver failure is supportive*
- prognosis is generally good after removal of offending agent[3]
- refer to liver transplantation center for encephalopathy, coagulopathy, or acute liver failure[3]
* other than acetaminophen
More general terms
More specific terms
Additional terms
References
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
- ↑ 2.0 2.1 2.2 Chalasani N et al. for the Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008 Dec; 135:1924. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18955056
- ↑ 3.0 3.1 3.2 3.3 3.4 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
- ↑ 4.0 4.1 Bjornsson ES et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013 Jun; 144:1419. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23419359
- ↑ Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006 Feb 16;354(7):731-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16481640
- ↑ 6.0 6.1 Fontana RJ et al. Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology 2014 Jul; 147:96 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24681128
- ↑ Ghabril M, Chalasani N, Bjornsson E Drug-induced liver injury: a clinical update. Curr Opin Gastroenterol. 2010 May;26(3):222-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20186054
- ↑ Bjornsson E Review article: drug-induced liver injury in clinical practice. Aliment Pharmacol Ther. 2010 Jul;32(1):3-13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20374223
- ↑ Verma S, Kaplowitz N. Diagnosis, management and prevention of drug-induced liver injury. Gut. 2009 Nov;58(11):1555-64. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19834119
- ↑ 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 Sep;137(3):856-64, 864.e1. Erratum in: Gastroenterology. 2013 Sep;145(3):695. Dosage error in article text. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19524577
- ↑ 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 Jul;109(7):950-66; PMID: https://www.ncbi.nlm.nih.gov/pubmed/24935270
- ↑ Hoofnagle JH, Bjornsson ES. Drug-Induced Liver Injury - Types and Phenotypes. N Engl J Med 2019; 381:264-273, July 18 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31314970 https://www.nejm.org/doi/full/10.1056/NEJMra1816149
- ↑ 13.0 13.1 13.2 Torgersen J, Mezochow AK, Newcomb CW et al Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data. JAMA Intern Med. 2024 Jun 24:e241836. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38913369 PMCID: PMC11197444 Free PMC article. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2820267