-Step 1: Repeat CMP while fasting to confirm that the ALP is truly elevated. Also, check to make sure that it’s not from something physiologic such as pregnancy or a post-prandial increase. If the repeat ALP is within normal limits, continue to monitor the patient and repeat CMP in 6-12 months. If it’s still elevated, go to step 2.
-Step 2: Order GGT (gamma-glutamyl transferase) or 5′-Nucleosidase to confirm that the elevated ALP is of hepatic origin.
If GGT is normal when ALP elevation is noted, the liver is not the cause. Evaluate for bone disease including bone metastases. If GGT is elevated along with ALP, then, injury to the hepatic bile ducts is implicated. In that case, go to step 3 below.
-Step 3: RUQ U/S: Get RUQ ultrasonography to assess the hepatic parenchyma and bile ducts and distinguish between intrahepatic and extrahepatic cholestasis. If U/S shows dilated bile ducts, then get MRCP or ERCP. If there is no biliary ductal dilatation, check AMA (antimitochondrial antibodies).
Refer to a gastroenterologist or hepatologist if the patient has persistent liver test elevations (≥2 times the ULN for ALT and AST or 1.5 times ULN for Alk phos). Also, refer patients who are being considered for liver biopsy. “We use a conservative estimate for the upper limit of normal for aminotransferases (approximately 30 international unit/L for men and 20 international unit/L for women) since the higher limits reported by many laboratories likely underestimate the degree of aminotransferase elevation.” UTD
**You only get a GGT to confirm the hepatic source of ALP if other liver chemistries and markers of function like ALT, AST, bilirubin etc are normal.
If Alk phos is elevated but GGT or 5′-nucleosidase is normal, you should evaluate for bone disease.
“An elevated bone ALP is indicative of high bone turnover, which may be caused by several disorders including healing fractures, osteomalacia, hyperparathyroidism, hyperthyroidism, Paget disease of bone, osteogenic sarcoma, and bone metastases. Refer those patients to an endocrinologist for evaluation. Initial testing may include measurement of serum calcium, parathyroid hormone, 25-hydroxyvitamin D, and imaging with bone scintigraphy.” UTD
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From Normal to significant elevations of ALP.
“-Abnormal levels of hepatic enzymes including ALP may be found in up to 6% of well adults, whereas liver disease will be found only in about 1% of the general population. This likely reflects the fact that what is considered the acceptable range of values for ALP and other hepatic enzymes reflects a population-based norm; outliers without significant disease should be expected. In addition, minor ALP elevation often occurs because of improper handling of the specimen and delayed testing. ALP may increase in a sample by as much as 5% to 10% after 4 hours of storage. A clinically evident cause is usually noted with marked ALP elevation (> 3 times upper limit of normal [ULN]).
–ALP measurement at up to 2 times ULN is found in hepatitis and heavy alcohol consumption. Marked ALP elevation is usually noted with extrahepatic biliary obstruction, primary biliary cirrhosis, and infiltrative processes such as neoplasm. Less dramatic ALP elevation can be seen in infectious mononucleosis, bile duct obstruction, hepatitis, heavy alcohol consumption, and fatty liver.
-Childhood ALP measures are often up to 3 times those of adult levels, influenced by bone growth and high levels of this ALP fraction.” Medscape.
“Common causes of minor ALP elevation in the asymptomatic adult primary include drug or alcohol-induced liver disease and fatty liver. ALP should return to normal within 2-8 weeks of the withdrawal of the offending drug or discontinuation of alcohol use.” If the mild elevation is because of fatty liver, weight loss will cause it to resolve.
Explanation.
Elevated alkaline phosphatase is a marker of cholestasis and suggests a reduction in bile flow. An elevation of alkaline phosphatase is seen in more than 90% of patients with cholestasis. It also is elevated in infiltrative disorders or fungal infections of the liver, often quite strikingly, with levels above 1000 U/L.
ALP isozymes are present in other human tissues including the liver, bone, small intestines, kidneys, placenta, and white blood cells. Because of that, a high alkaline phosphatase is not specific for the biliary tract disease.
Even though it’s possible to determine the source by measuring and distinguishing the different ALP isozymes, this process requires electrophoretic tests that are not usually available clinically.
GGT (Gamma-glutamyl transpeptidase) is found primarily in the liver and kidneys and if elevated helps indicate a biliary source. 5′-nucleotidase, or leucine aminopeptidase also serve the same function as GGT.
High ALP doesn’t simply come from mechanical biliary obstruction but also new ALP is made and backs up into the circulation. Because of that, an elevation of alkaline phosphatase may be delayed in the setting of acute obstruction.
***Liver Function Tests — AST, ALT, and ALT don’t really measure hepatic function. They evaluate hepatocyte integrity. When liver cells are injured, these enzymes become elevated.
Sources:
https://www.uptodate.com/contents/approach-to-the-patient-with-abnormal-liver-biochemical-and-function-tests (This article has an algorithm for working up elevated ALP)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341633/
http://emedicine.medscape.com/article/171386-workuphttp://www.medscape.com/viewarticle/413420
http://www.medscape.com/viewarticle/413420