Hepatic Failure/GI/Endocrine Emergencies

Unlike most other types of drug-induced liver injury (DILI), acetaminophen-induced liver failure

is dose-dependent and predictable, and it is typically associated with doses above 10 g/day (or

more than 200 mg/kg/day) in 24 hours or more than 6 g/day (around 150 mg/kg/day) for 48 hours

in adults.

Rates of ALF caused by acetaminophen have increased during the previous 2 decades.

is around 20%–40%.

Acetaminophen-induced ALF typically presents as hyperacute liver failure and is defined by four

stages of progression:

Preclinical: Occurs within the first 24 hours of ingestion. Typically associated with minimal or

no signs or symptoms of hepatotoxicity

ii.

Injury: Occurs 24–72 hours after ingestion. Associated with marked elevation in liver

transaminases

iii.

Failure: Occurs 72–96 hours after ingestion. Associated with peak liver injury including

encephalopathy, coagulopathies, and jaundice

iv.

Recovery: Occurs 1 week after ingestion if patient survives through failure stage. Recovery

may be prolonged in critically ill patients who present with fulminant liver failure.

Additional information on background, pathophysiology, and treatment of acetaminophen overdose

can be found in the Toxicology review chapter.

DILI

The incidence of DILI caused by drugs other than acetaminophen is rare, at a rate of

approximately 11% of ALF cases per year.

ii.

Unlike acetaminophen-induced liver failure, DILI is rarely the result of dose-related toxicity,

and most cases are idiosyncratic.

iii.

DILI typically presents as a subacute ALF, with most cases occurring within the first 6 months

after drug initiation. However, some drugs (e.g., nitrofurantoin, minocycline, statins) have the

potential to cause DILI 6 months or more after initiation.

iv.

Transplant-free survival is low for these patients (about 30%), and most patients will require

transplantation.

DILI is ultimately a diagnosis of exclusion. The American College of Gastroenterology (ACG)

guidelines for the management of DILI recommend a specific workup for viral hepatitis,

autoimmune hepatitis, Wilson disease, and Budd-Chiari syndrome before diagnosis of DILI.

vi.

To identify potential culprit medications, a detailed patient medication history should be

obtained, including herbal medications. Classes of drugs commonly associated with DILI

include antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticonvulsants,

which together account for almost two-thirds of those attributable to DILI.

vii.

Scoring systems such as the RUCAM (Roussel Uclaf Causality Assessment Method) have

been developed to assess the causality attribution for suspected DILI. These scoring systems

give points on the basis of timing of exposure and liver function tests, risk factors for DILI,

competing medications and diagnoses, and rechallenge information. Higher scores indicate a

higher likelihood of drug cause.