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1
Question:

A 35-year-old woman is brought to the emergency department due to 3 days of progressive nausea, anorexia, malaise, abdominal pain, and lethargy.  The patient is a chronic carrier of hepatitis B virus and has not received any treatment.  She has a history of injection drug use and completed a rehabilitation program 2 years ago, but recently started using drugs again.  She drinks alcohol but does not use tobacco.  Her temperature is 37.8 C (100.2 F), blood pressure is 106/64 mm Hg, and pulse is 114/min.  Mild tender hepatomegaly is present.  Laboratory testing shows markedly elevated serum aminotransferase levels and a positive serum hepatitis D antigen.  Acute liver failure due to hepatitis D virus superinfection is suspected.  Which of the following is required to make a diagnosis of acute liver failure in this patient?

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Explanation:

Acute liver failure

Etiology

  • Viral hepatitis (eg, HSV; CMV; hepatitis A, B, D, E)
  • Drug toxicity (eg, acetaminophen overdose, idiosyncratic)
  • Ischemia (eg, shock liver, Budd-Chiari syndrome)
  • Autoimmune hepatitis
  • Wilson disease
  • Malignant infiltration

Clinical presentation

  • Generalized symptoms (eg, fatigue, lethargy, anorexia, nausea)
  • Right upper quadrant abdominal pain
  • Pruritus & jaundice due to hyperbilirubinemia
  • Renal insufficiency
  • Thrombocytopenia
  • Hypoglycemia

Diagnostic requirements

  • Severe acute liver injury (ALT & AST often >1,000 U/L)
  • Signs of hepatic encephalopathy (eg, confusion, asterixis)
  • Synthetic liver dysfunction (INR ≥1.5)

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CMV = cytomegalovirus; HSV = herpes simplex virus; INR = international normalized ratio.

Acute liver failure (ALF) is a serious condition characterized by severe acute liver injury in a patient without cirrhosis or underlying liver disease.  The diagnosis requires:

  • Severe acute liver injury as evidenced by elevated aminotransferases (often >1000 U/L)
  • Signs of hepatic encephalopathy (HE)
  • Impaired hepatic synthetic function (defined as INR >1.5)

The presence of HE differentiates ALF from acute hepatitis, which has a much better prognosis than ALF.  In addition to varying degrees of HE, other common manifestations of ALF include fatigue, lethargy, nausea, vomiting, jaundice, pruritus, and right upper quadrant pain.  The most common causes of ALF are drug toxicity (eg, acetaminophen overdose) and acute viral hepatitis (eg, hepatitis A virus, hepatitis B virus [HBV]).  Other causes include autoimmune hepatitis, ischemia, Wilson disease, and malignant infiltration of the liver.

Chronic HBV carriers, such as this patient, typically remain asymptomatic without evidence of underlying liver disease (eg, fibrosis).  In the presence of HBV, acute superinfection with hepatitis D virus carries a high risk of ALF development, particularly in intravenous drug users.  On further evaluation of this patient, clinical signs of HE and laboratory findings of INR >1.5 would be diagnostic of ALF.

(Choices A and B)  Decreased urine output (due to intravascular volume depletion and decreased renal perfusion) and elevated portal venous pressure (due to increased resistance to blood flow through the inflamed liver) are both common in ALF.  However, neither is specific for ALF or part of the diagnostic criteria.

(Choice C)  Features of liver cirrhosis include fluid retention, jaundice, caput medusae, palmar erythema, muscle wasting, and gynecomastia.  ALF includes some of these features (eg, jaundice, fluid retention), but it is characterized by acute liver injury in a patient without cirrhosis.

(Choice D)  Severe hyperbilirubinemia is common in ALF and results from a combination of impaired conjugation and impaired excretion of bilirubin.  However, it is not a requirement for the diagnosis of ALF.

Educational objective:
Acute liver failure is defined as acute onset of severe liver injury with encephalopathy and impaired synthetic function (defined as INR >1.5) in a patient without cirrhosis or underlying liver disease.  Drug toxicity and acute viral hepatitis are the most common causes.