Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 32-year-old woman is evaluated for a 10-day history of malaise, right upper quadrant discomfort, and progressive jaundice. She has had no recent travel outside of the United States, does not drink alcohol, and has no recent ingestions of drugs, including acetaminophen or herbal remedies. Up until this time, she has been healthy. She has a history of type 1 diabetes mellitus for which she takes insulin glargine and insulin detemir. She has no other medical problems.

On physical examination, temperature is 37.5 °C (99.5 °F), blood pressure is 106/68 mm Hg, pulse rate is 90/min, and respiration rate is 18/min. BMI is 24. Mental status is normal. Jaundice and scleral icterus are noted. Abdominal examination reveals tender hepatomegaly.

Laboratory studies:

INR	0.9 (normal range, 0.8-1.2)
Albumin	3.8 g/dL (38 g/L)
Alkaline phosphatase	220 units/L
Alanine aminotransferase	920 units/L
Aspartate aminotransferase	850 units/L
Total bilirubin	14.4 mg/dL (246.2 µmol/L)
Direct bilirubin	10.6 mg/dL (181.3 µmol/L)

Abdominal ultrasound demonstrates hepatic enlargement with edema surrounding the gallbladder. There is no biliary ductal dilatation. The portal vein and spleen are normal.

Which of the following is the most likely diagnosis?

A. Acute viral hepatitis
B. Fulminant liver failure
C. Hemochromatosis
D. Primary biliary cirrhosis

MKSAP Answer and Critique

The correct answer is A. Acute viral hepatitis.

The most likely diagnosis is acute viral hepatitis. This patient has marked hepatitis with jaundice and significant elevations of hepatic aminotransferases (greater than 15 times the upper limit of normal). In addition, the short duration of her symptoms suggests an acute onset. Elevation of aspartate aminotransferase and alanine aminotransferase to this severe degree is seen in acute viral hepatitis. Typically, the only other causes of this degree of liver chemistry test elevation are medication reactions/toxicity, autoimmune liver disease, ischemic hepatitis (referred to as “shock liver”), or acute bile duct obstruction.

Fulminant liver failure should always be a consideration in patients with acute hepatitis. However, fulminant liver failure is manifested by hepatic encephalopathy that occurs within 8 weeks of the onset of jaundice; this patient has normal mental status. In addition, laboratory studies demonstrate a normal INR and normal albumin level, confirming that this patient’s liver function remains intact despite her liver inflammation.

Hemochromatosis is a chronic metabolic cause of chronic liver disease and is associated with much lower elevations of liver inflammation markers than are seen in this patient.

Primary biliary cirrhosis is an immune-mediated cause of chronic liver inflammation. This is not the correct diagnosis because the degree of elevation of aminotransferases vastly exceeds the levels seen in patients with primary biliary cirrhosis, who have elevated alkaline phosphatase and bilirubin levels disproportionately higher than the aminotransferase elevation.

Key Point

• Acute viral hepatitis is characterized by jaundice and significant elevations of hepatic aminotransferases (greater than 15 times the upper limit of normal).

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