Workup of Elevated Alkaline Phosphatase

Step 1: Confirm Hepatobiliary Origin

The American Gastroenterological Association recommends measuring GGT and/or performing alkaline phosphatase isoenzyme fractionation to determine if the elevated ALP is of hepatobiliary origin 1, 2
5'-nucleotidase can also be obtained, although it is less commonly used 2

The American College of Gastroenterology suggests reviewing medication history for potential drug-induced causes 3
Assess risk factors for liver disease, alcohol consumption, and comorbid conditions, as recommended by the American Association for the Study of Liver Diseases 3
Obtain additional liver function tests, including aminotransferases (ALT, AST) 3, bilirubin (total and direct) 2, albumin and prothrombin time (to assess synthetic function) 4

If hepatobiliary origin is suspected, the American College of Radiology recommends abdominal ultrasound to evaluate for biliary obstruction and parenchymal liver disease 5
Consider serologic testing for common hepatic diseases, including viral hepatitis markers and autoimmune markers, as suggested by the American Association for the Study of Liver Diseases 3, 1
If initial evaluation is unrevealing, consider MR cholangiography or endoscopic retrograde cholangiography to evaluate for primary sclerosing cholangitis or dominant stricture 2

If malignancy is suspected, the National Comprehensive Cancer Network recommends considering CT chest/abdomen/pelvis to evaluate for primary malignancy or metastatic disease 6
Consider bone scan if bone metastases are suspected, as recommended by the National Comprehensive Cancer Network and the American Urological Association 6, 7
If initial workup is unrevealing, consider liver biopsy for persistently elevated ALP without clear cause, especially if other liver tests are abnormal, as suggested by the American Association for the Study of Liver Diseases 3

The American Gastroenterological Association recommends obtaining viral hepatitis markers (HAV-IgM, HBsAg, HBcIgM, HCV antibody) in patients with confirmed hepatobiliary ALP elevation 8
The American Gastroenterological Association suggests that in patients with chronic elevations (≥6 months), more complete serologic and radiologic evaluations are warranted 8
For asymptomatic patients with mild elevations, unremarkable physical examinations, and intact hepatic function, close clinical follow-up is reasonable if initial studies are unrevealing, as recommended by the American Gastroenterological Association 8
However, patients with significant symptoms, evidence of chronic or decompensated liver disease, or severe chemistry abnormalities require complete and expeditious evaluation, according to the American Gastroenterological Association 8