Acute Liver Injury and Failure Flashcards
Acute liver injury
o Sudden onset of severe hepatocellular damage in a previously healthy liver
o Sudden substantial loss of hepatocytes
o Acute increase in previously normal liver aminotransferases: ALT and AST >10-25x ULN
o Variable effects on hepatic functions
o Causes: toxins, viral infection, ischemia, malignancy, inherited diseases, idiopathic
3 possible outcomes:
• Full recovery with no long-term sequelae
• Clinical recovery but continued laboratory evidence of ongoing chronic liver injury (chronic hepatitis) that can progress to cirrhosis
• Severe liver failure → death without transplantation
Acute liver failure
Acute liver injury accompanied by impaired hepatic synthetic function:
• Increased PT/INR (INR >1.5)
• Elevation in serum total bilirubin
Most severe form = fulminant liver failure/fulminant hepatic failure
• Altered mental status (encephalopathy)
• Severe coagulopathy
• Often fatal
• Cerebral edema → increased intracranial pressure → permanent cerebral injury and death
Acute hepatitis
o Acute inflammatory injury within the liver
o Causes: viruses, autoimmune liver disease, drugs (alpha-methyl dopa, INH), toxins (ethanol), metabolic (Wilson’s disease, pregnancy), other (amanita mushrooms)
Differentiate between intrinsic and idiosyncratic drug induced liver injury
Intrinsic hepatotoxicity:
o Predictable and dose-dependent
o Ex: acetaminophen
Idiosyncratic reactions:
o Unpredictable
o Reflect an interaction between the medication and the patient’s unique genetic makeup, immune mechanisms, or aberrant metabolism
o Little relationship to dosage, duration or severity of injury
Explain the mechanism of acetaminophen hepatotoxicity and why N-acetylcysteine administration is effective in toxicity prevention.
- Most common cause of acute liver failure in U.S.
- Toxicity from excessive formation or impaired conjugation of NAPQI
2 exacerbating factors:
Conditions that induce cytochrome P450 pathway
• Ex: chronic alcohol ingestion, certain medications
Malnutrition → depleted glutathione stones and decreased capacity to bind NAPQI metabolites → promotes acetaminophen liver injury
Lab findings:
o Elevated aminotranferases: ALT and AST > 1000 IU/ML
o PT/INR prolongation
o Serum bilirubin = only modestly elevated relative to other liver tests
Treatment
o N-acetylcysteine (NAC) = restores hepatic glutathione stores → increased conjugation of NAPQI
Common medications causing acute liver injury
o Amanita phalloides (Mushroom poisoning)
o Amoxicillin/Clavulanate (Augmentin)
o Halogenated volatile anesthetics (especially Halothane)
o Isoniazid (INH)
o Methyldopa
o Valproate
o Monoamine oxidase inhibitors
Budd-Chiari Syndrome
Potential cause of acute liver injury
(hepatic venous outflow obstruction) • Acute obstruction of hepatic veins • Typically by thrombosis • Painful hepatomegaly and ascites • More common in females • Many have underlying thrombophilic condition (ex: oral contraceptive use)
Autoimmune Hepatitis
- Circulating autoAbs and inflammation of hepatic parenchyma
- Usually presents as chronic hepatitis but can present as acute liver injury/failure
- Female predominance
- Occurs at any age
- Labs: elevated ANA (antinuclear Ab), ASMA (anti-smooth muscle Ab), IgG
Describe hepatic encephalopathy and explain its importance in acute liver failure
Definition
o Development of clouded cognition and altered level of alertness in setting of advanced liver failure
Spectrum of symptoms: mild confusion → coma
o Often have jaundice and asterixis (flapping tremor)
Contributing causes:
o Impaired toxin clearance (ammonia), cerebral atrophy/edema, metabolic abnormalities, changes in cerebral perfusion
Cerebral edema → increased intracranial pressure
• Most dangerous complication of acute liver failure
• May cause permanent cerebral injury and death
• Presents with seizures, changes in pupillary responses, and cerebral posturing
