Adverse drug reactions in children are uncommon. Nevertheless, drug-induced
hepatotoxicity, when it occurs, must be promptly recognized, and
the offending agent discontinued, although cessation does not always
result in rapid recovery. Delays in recognizing hepatic injury may
significantly contribute to morbidity, resulting in a need for liver
transplantation or in death.1-5
The role of the liver in the processing or biotransformation
of xenobiotics (foreign substances) is discussed in Chapter 418. Mechanisms of hepatoxicity vary, as they depend on the
drug, dosage, and patient factors such as age, gender, nutrition,
and genetic predisposition. In general, medicinal and environmental
agents known to cause hepatotoxicity have been characterized as
predictable (intrinsic) or unpredictable (idiosyncratic) hepatotoxins.
The patterns of liver injuries are clinically and histopathologically
diverse (Table 422-1).
422-1. Clinical and Pathologic Findings in
Drug-Induced Liver Disease in Children |Favorite Table|Download (.pdf)
422-1. Clinical and Pathologic Findings in
Drug-Induced Liver Disease in Children
|Drug*||Biochemical Response†||Pathologic Finding||Risk Factors||Clinical Characteristics|
|Acetaminophen||8–500×||<3×||Zone 3 necrosis||Dose, ↑ age, fasting||Dose-dependent injury, initial nausea and vomiting; jaundice
and coagulopathy if liver failure|
|Amiodarone||1–5×||V×||Steatohepatitis, phospholipidosis||Dose, duration of therapy||Asymptomatic elevation of ALT and AST common; cirrhosis and
liver failure rare|
|Amoxicillin/clavulanic acid||>3×||>3×||Cholestasis, hepatitis||↑ age, duration of therapy||Clavulanic acid is likely cause of toxicity; most cases recover
fully but rare cases of progressive ductopenia with cirrhosis reported
|Aspirin||3–20×||<3×||Nonzonal necrosis, steatosis (Reye)||Dose, rheumatoid disease||Dose dependent, rapid recovery if drug discontinued; ↑ risk
of Reye syndrome in febrile children|
|Azathioprine/6-MP||>3×||>3×||Cholestasis, hepatitis||Transplantation||Cholestasis more common with azathioprine; portal HTN and
vascular injury also reported|
|Carbamazepine||>3×||V×||Hepatitis (children), granulomatosis||Metabolic idiosyncrasy||Hepatitis associated with drug hypersensitivity syndrome|
|Cyclosporine||<3×||>3×||Cholestasis||CYP interactions, dose||Direct hyperbilirubinemia more common, mixed hepatitis/cholestasis
at higher doses|
|Erythromycin||<3×||>3×||Hepatitis/cholestasis||↑ age||Anorexia, nausea, jaundice, and abdominal pain; all forms of
erythromycin reported buy erythromycin estolate more common in adults
(1%–2% develop jaundice)|
|Estrogens||<5×||<3×||Cholestasis||Dose||Insidious onset of mild jaundice and pruritus; hepatic vein thrombosis,
hepatic adenoma with prolonged use|
|Halothane||8–500×||<3×||Acute hepatitis (zone 3 necrosis)||↑ age, female gender, repeated exposure||Rare in children; mild ↑ ALT in 10%–20% of
adults; severe hepatitis and liver failure (fatal in 14%–71%)|
|Isoniazid||8–500×||<3×||Acute hepatitis||↑ age, dose?||More common in adults; mild ↑ ALT in 7%–17% of
children; use of CYP inducers may increase toxicity risk|
|Ketoconazole||>3×||V×||Zone 3 necrosis||↑ age, female gender||Symptoms of hepatitis and jaundice after 6–8 wk
of therapy; cause by metabolic idiosyncrasy|
|Methotrexate||1–3×||1–3×||Steatosis and fibrosis||Obesity, ↑dose, type 2 diabetes||Risk of fibrosis with normal ALT; surveillance liver biopsy
after high cumulative dose|
|Minocydine||>3×||<3×||Hepatocellular necrosis||Use <6 mo, female gender||SLE-like syndrome or chronic hepatitis with ...|
Log In to View More
If you don't have a subscription, please view our individual subscription options below to find out how you can gain access to this content.
Want remote access to your institution's subscription?
Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.
If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.
AccessPediatrics Full Site: One-Year Subscription
Connect to the full suite of AccessPediatrics content and resources including 20+ textbooks such as Rudolph’s Pediatrics and The Pediatric Practice series, high-quality procedural videos, images, and animations, interactive board review, an integrated pediatric drug database, and more.
Pay Per View: Timed Access to all of AccessPediatrics
24 Hour Subscription $34.95
48 Hour Subscription $54.95
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.