Gastroenterology · Hepatology
The facts most likely to be tested
Acute liver failure is defined by the triad of elevated aminotransferases, hepatic encephalopathy, and impaired synthetic function (INR ≥ 1.5) in a patient without pre-existing cirrhosis.
Acetaminophen toxicity is the most common cause of acute liver failure in the United States, often presenting with massive aminotransferase elevation (> 3,000 IU/L).
Cerebral edema is the most common cause of death in patients with acute liver failure and is driven by intracranial hypertension.
N-acetylcysteine is the definitive antidote for acetaminophen-induced acute liver failure and provides benefit even in non-acetaminophen etiologies by improving hemodynamics and oxygen delivery.
Lactulose is the first-line treatment for hepatic encephalopathy to reduce ammonia absorption in the gut.
King's College Criteria are used to determine the necessity for urgent liver transplantation based on pH, creatinine, INR, and grade of encephalopathy.
Hypoglycemia is a frequent and life-threatening metabolic complication of acute liver failure due to depleted hepatic glycogen stores and impaired gluconeogenesis.
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A 24-year-old female is brought to the emergency department by her roommate after being found confused and lethargic. She has no significant past medical history but admits to taking a large amount of 'pain pills' 48 hours ago following a breakup. Physical examination reveals jaundice, asterixis, and right upper quadrant tenderness. Laboratory studies show an ALT of 4,200 IU/L, AST of 3,800 IU/L, and an INR of 2.1.
What is the most appropriate next step in the management of this patient?
Administration of N-acetylcysteine
The patient meets the criteria for acute liver failure (elevated enzymes, encephalopathy, and coagulopathy) secondary to acetaminophen toxicity, requiring immediate initiation of N-acetylcysteine to replenish glutathione stores.
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Etiology / Epidemiology
Most common cause is acetaminophen toxicity. Characterized by rapid onset of encephalopathy and coagulopathy in a patient without pre-existing cirrhosis.
Clinical Manifestations
Presents with jaundice, asterixis, and altered mental status. Cerebral edema is the most feared complication.
Diagnosis
Defined by INR ≥ 1.5 and any degree of encephalopathy within 26 weeks of injury.
Treatment
N-acetylcysteine is the antidote for acetaminophen; liver transplantation is the definitive treatment for non-acetaminophen causes.
Prognosis
High mortality without transplant. King's College Criteria used to determine transplant candidacy.
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Epidemiology & Etiology
Acute liver failure (ALF) is a rare but catastrophic syndrome. Acetaminophen toxicity accounts for nearly 50% of cases in the US. Other causes include viral hepatitis (A, B, E), idiosyncratic drug reactions, and Budd-Chiari syndrome.
Pertinent Anatomy
The liver's massive functional reserve masks early injury. Once hepatocyte necrosis exceeds 80-90%, synthetic function fails, leading to rapid metabolic collapse.
Pathophysiology
Massive necrosis triggers a systemic inflammatory response. Failure of ammonia detoxification leads to cerebral edema and intracranial hypertension. Impaired synthesis of clotting factors results in coagulopathy.
Clinical Manifestations
Patients present with jaundice, asterixis (flapping tremor), and confusion. Cerebral edema is the primary cause of death. Monitor for seizures and pupillary dilation as signs of impending herniation.
Diagnosis
Diagnosis requires INR ≥ 1.5 and encephalopathy in a patient without underlying liver disease. Serum acetaminophen levels must be checked in all patients. Liver biopsy is rarely indicated due to the high risk of bleeding.
Treatment
N-acetylcysteine is the first-line agent for acetaminophen toxicity and may benefit non-acetaminophen cases. Avoid sedatives that mask encephalopathy. Lactulose is used for encephalopathy, while liver transplantation is the only definitive therapy for irreversible failure.
Prognosis
Prognosis is poor without transplant. Use King's College Criteria to predict mortality. Monitor for multi-organ failure and sepsis as leading causes of death.
Differential Diagnosis
Acute viral hepatitis: elevated transaminases > 1000 IU/L
Budd-Chiari syndrome: hepatic vein thrombosis on Doppler
Wilson disease: low ceruloplasmin and Kayser-Fleischer rings
Autoimmune hepatitis: positive ANA or ASMA
Ischemic hepatitis: rapid rise and fall of AST/ALT after shock