Review Question - QID 104815

This patient is presenting with Dubin-Johnson syndrome as shown by his conjugated hyperbilirubinemia with dark granular pigment seen in hepatocytes on biopsy.

Dubin-Johnson syndrome is an autosomal recessive disorder that causes hepatocytes to lose their ability to secrete conjugated bilirubin. It is a benign disease and is often diagnosed early in infancy when abnormalities are noticed on labs or in the teenage years when it often presents as non-pruritic jaundice. It causes a conjugated hyperbilirubinemia with normal levels of AST and ALT. Rotor syndrome also presents with a conjugated hyperbilirubinemia, but the two can be differentiated based on liver biopsy. Dubin-Johnson will demonstrate dark granular pigments on biopsy while Rotor syndrome will not. Rather, rotor syndrome will display normal histology. Both conditions are relatively benign and do not limit lifespan nor require treatment.

Porter and Dennis review the diagnosis and management of hyperbilirubinemia in the term newborn. They state jaundice is considered pathologic if it presents within the first 24 hours after birth, the total serum bilirubin level rises by more than 5 mg per dL (86 micromol per L) per day or is higher than 17 mg per dL (290 micromol per L), or an infant has signs and symptoms suggestive of serious illness. The management goals are to exclude pathologic causes of hyperbilirubinemia and initiate treatment to prevent bilirubin neurotoxicity.

Johnston reviews the interpretation and significance of liver enzyme testing. He states they can be normal in patients with chronic hepatitis or cirrhosis. The normal range for aminotransferase levels is slightly higher in males, nonwhites, and obese persons. Severe alcoholic hepatitis is sometimes confused with cholecystitis or cholangitis. Conversely, patients who present soon after passing common bile duct stones can be misdiagnosed with acute hepatitis because aminotransferase levels often rise immediately, but alkaline phosphatase and gamma-glutamyltransferase levels do not become elevated for several days.

Figure A demonstrates scleral icterus seen in jaundice. Figure B is a liver biopsy with dark granular pigments characteristic of Dubin-Johnson syndrome.

Incorrect answers:
Answer 2: Gilbert's syndrome would be expected to cause an increase in unconjugated (indirect) bilirubin.
Answer 3: Rotor syndrome would also present with a conjugated hyperbilirubinemia similar to Dubin-Johnson. However, dark granular pigments are NOT observed in the liver biopsies of patients with Rotor syndrome.
Answer 4: Crigler-Najjar syndrome would be expected to cause an increase in unconjugated (indirect) bilirubin.
Answer 5: Hepatitis C would be expected to cause an increase in ALT and AST. However, this patient's ALT and AST are normal.