Emergency: requires immediate attention
Drug-induced hepatotoxicity
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Synopsis

Hepatotoxicity is a possible consequence of ingestion of any medication including pharmacologic agents, complementary and alternative medications (CAMs), and industrial toxins. Drug-induced hepatotoxicity refers to liver injury resulting from drug ingestion. Patients can present with a range of symptoms; many are asymptomatic while others have sequelae of acute liver failure. Drug-induced liver injury can lead to hepatocellular injury (primarily transaminase elevation), cholestatic injury (alkaline phosphatase, primarily total / direct bilirubin elevation), or a mixed pattern. This determination is often made based on laboratory abnormalities. Any injury pattern can lead to liver failure, characterized by impairment in the liver's synthetic function (thrombocytopenia, coagulopathy).
Drug-induced hepatoxicity can be direct (eg, acetaminophen, niacin, aspirin, cocaine, intravenous [IV] amiodarone, IV methotrexate, chemotherapy), idiosyncratic (eg, amoxicillin-clavulanate, cephalosporins, isoniazid, nitrofurantoin, minocycline, fluoroquinolones, macrolide antibiotics), or indirect (eg, antineoplastic agents, glucocorticoids, certain monoclonal antibodies, protein kinase inhibitors).
Hallmarks of therapy include removal of the offending agent and supportive care. Particular drug-related injuries (eg, acetaminophen overdose) benefit from administration of the hepato-protective medication N-acetylcysteine.
For a list of medications associated with drug-induced hepatotoxicity, see Drug Reaction Data below. The National Library of Medicine maintains a searchable database, LiverTox, with a comprehensive list of agents and drug classes.
Related topics: drug-induced jaundice, drug-induced splenomegaly
Drug-induced hepatoxicity can be direct (eg, acetaminophen, niacin, aspirin, cocaine, intravenous [IV] amiodarone, IV methotrexate, chemotherapy), idiosyncratic (eg, amoxicillin-clavulanate, cephalosporins, isoniazid, nitrofurantoin, minocycline, fluoroquinolones, macrolide antibiotics), or indirect (eg, antineoplastic agents, glucocorticoids, certain monoclonal antibodies, protein kinase inhibitors).
Hallmarks of therapy include removal of the offending agent and supportive care. Particular drug-related injuries (eg, acetaminophen overdose) benefit from administration of the hepato-protective medication N-acetylcysteine.
For a list of medications associated with drug-induced hepatotoxicity, see Drug Reaction Data below. The National Library of Medicine maintains a searchable database, LiverTox, with a comprehensive list of agents and drug classes.
Related topics: drug-induced jaundice, drug-induced splenomegaly
Codes
ICD10CM:
K71.9 – Toxic liver disease, unspecified
SNOMEDCT:
197354009 – Toxic liver disease
K71.9 – Toxic liver disease, unspecified
SNOMEDCT:
197354009 – Toxic liver disease
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
- Acute or chronic viral hepatitis (eg, hepatitis A, B, C, D, E, Epstein-Barr virus, cytomegalovirus, herpes simplex virus, varicella zoster virus, adenovirus)
- Autoimmune hepatitis
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Nonalcoholic steatohepatitis (see nonalcoholic fatty liver disease)
- Alcoholic steatohepatitis (see alcoholic hepatitis)
- Systemic lupus erythematosus
- Shock liver secondary to cardiovascular causes, especially right-sided heart failure (see congestive hepatopathy)
- Cholecystitis
- Cholangitis
- Budd-Chiari syndrome
- Wilson disease
- Cholestatic liver disease
- Pregnancy-related conditions of liver, eg, acute fatty liver of pregnancy, intrahepatic cholestasis of pregnancy
- Malignancy (especially hepatocellular carcinoma and lymphoma)
- Hemochromatosis
- Sarcoidosis
- Hepatic artery thrombosis
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
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References
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Last Reviewed:01/02/2018
Last Updated:07/09/2020
Last Updated:07/09/2020