Abnormal Liver Function Tests: Elevated Serum Bilirubin and/or Predominant Elevations in ALP, 5'-NT, and/or Gamma Glutamyltransferase (GGT)

Differential Diagnosis

Red blood cell (RBC) hemolysis from a variety of causes

Obstruction of the biliary tract from any of the several possibilities

Intrahepatic biliary diseases: primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)

Hereditary conjugated hyperbilirubinemias: Dubin-Johnson syndrome, Rotor syndrome

Hereditary unconjugated hyperbilirubinemias: Criggler-Najjar syndrome type I, Criggler-Najjar syndrome type II, Gilbert syndrome

Suggested Additional Lab Testing

Tests to identify common causes of elevated bilirubin, such as hepatitis, are useful.

Perform tests for liver function in addition to total and unconjugated bilirubin, including AST, ALT, alkaline phosphatase, albumin, GGT, or 5´-nucleotidase, among others.

Tests to rule out RBC hemolysis as a cause for increased bilirubin are important.


  • Very high alkaline phosphatase and GGT or 5´-nucleotidase, with smaller elevations in AST and ALT

  • Positive anti-mitochondrial antibody test in 95% of PBC patientts


  • Alkaline phosphatase, GGT, 5´-nucleotidase, ALT, and AST elevations similar to those found in PBC

Rotor syndrome

  • Total bilirubin and unconjugated bilirubin usually 2-5 mg/dL, with at least 50% of the bilirubin conjugated

  • Coproporphyrin excretion in urine increased 2.5- to 5-fold over normal healthy controls

Criggler-Najjar syndrome type I

  • Markedly elevated total bilirubin (15 to >50 mg/dL) with essentially all of the bilirubin unconjugated

  • Liver function tests within the normal range

  • Total bilirubin values for type II typically lower than Criggler-Najjar type I; type II, the bilirubin is almost all unconjugated, as in the type I disorder.

Gilbert syndrome

  • Total bilirubin concentration usually less than 3 mg/dL; essentially all is unconjugated with normal liver function tests

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