A few comments on the use of liver function tests are indicated. It is not necessary to order every test available and keep repeating them all, even those that give essentially the same information. For example, the ALT is sometimes useful in addition to the AST either to establish the origin of an increased AST value (because ALT is more specific for liver disease) or to obtain the AST/ALT ratio when this ratio might be helpful. However, once the results are available, it is rarely necessary to repeat the ALT because it ordinarily does not provide additional assistance to the AST in following the course of the patient’s illness, nor will repetition add much additional useful information to assist diagnosis. The same is true of an elevated ALP level and the use of ALP test substitutes that are more specific for liver disease (gamma glutamyl transferase [GGT]; 5-nucleotidase [5-NT];). Whichever additional enzyme of this group is used, a normal result suggests that bone rather than liver is the source of the increased ALP level and the ALP level alone can be followed without repeating the other enzyme. If the AST level is moderately or markedly elevated and there are obvious signs of liver disease such as jaundice, it would be useless to assay GGT or 5-NT even once for this purpose, since both of them are likely to be elevated regardless of the cause of the liver disease and regardless of bone contribution to ALP. Therefore, rather than enzyme differentiation, many prefer ALP isoenzyme fractionation, which has the added benefit that concurrent elevation of both bone and liver fractions can be demonstrated. For this purpose, ALP isoenzyme electrophoresis is more reliable.

Aminotransferases of Liver Origin Elevated Over 6 Months Duration
Chronic active hepatitis virus hepatitis
Fatty liver (hepatic steatosis)
Wilson’s disease
Hemochromatosis
Alpha-1 antitrypsin deficiency
Drug-induced
Alcohol-associated (“active cirrhosis”)
Primary biliary cirrhosis
Autoimmune chronic active hepatitis

Isolated Elevation of Alkaline Phosphatase
ALP level increased
AST level normal
Total bilirubin level normal
Liver space-occupying lesions
Bone osteoblastic activity increased
Drug-induced (dilantin most common)
Intrahepatic cholestatic process in advanced stage of resolution
Pregnancy (third trimester)
Hyperthyroidism
Hyperparathyroidism

Serum cholesterol determination is not a very helpful liver function test, although a very high cholesterol level might add a little additional weight to the diagnosis of extrahepatic biliary tract obstruction or biliary cirrhosis. A urine bilirubin determination (“bile”) is not necessary if the serum conjugated bilirubin value is known. Serum protein electrophoresis may help to suggest cirrhosis, but it is not a sensitive screening test, and the pattern most suggestive of cirrhosis is not frequent. The PT as a liver function test is useful only in two situations: (1) an elevated PT not corrected by parenteral vitamin K suggests far-advanced liver destruction, and (2) an elevated PT that is corrected by vitamin K is some evidence for long-standing extrahepatic obstruction in a patient with jaundice. If all test results are normal and inactive cirrhosis is suspected, serum bile acid assay might be useful. The most frequent use for liver scan is to demonstrate metastatic carcinoma to the liver. Ultrasound (or CT scan)—and, in some cases, percutaneous transhepatic cholangiography—are helpful in differentiating extrahepatic from intrahepatic biliary tract obstruction. Liver biopsy can frequently provide a definitive diagnosis, thereby shortening the patient’s stay in the hospital and making lengthy repetition of laboratory tests or other procedures unnecessary. The earlier a biopsy is obtained, the more chance one has to see clear-cut diagnostic changes.

An initial liver test “profile” might include serum bilirubin, AST, and ALP determinations. If the serum bilirubin level is elevated, it could be separated into conjugated and unconjugated fractions. If the serum bilirubin level is not elevated, determining the GGT may be useful, both to help confirm liver origin for other test abnormalities or to suggest alcoholism if it is elevated out of proportion to the other tests. The PT may be useful if other tests are abnormal to provide a rough idea of the severity of disease. In some cases the results of the initial screening tests permit one to proceed immediately to diagnostic procedures. An AST value more than 20 times normal suggests hepatitis virus hepatitis, and specimens can be obtained for serologic tests diagnostic of acute hepatitis A, B, or C infection (e.g., hepatitis B surface antigen, hepatitis B core antibody-IgM, hepatitis A-IgM, hepatitis C antibody; see Chapter 17). A high bilirubin level or other evidence suggesting biliary tract obstruction can be investigated with biliary tract ultrasound or similar studies. A normal bilirubin level with significantly elevated ALP level not due to bone disease raises the question of metastatic tumor and may warrant a liver scan. If liver screening test results are abnormal but do not point toward any single diagnosis, a liver biopsy might be considered. Liver function tests could be repeated in 2-3 days to see if a significant change takes place, but frequent repetition of the tests and long delays usually do not provide much help in establishing a diagnosis. Also, there are a significant number of exceptions to any of the so-called diagnostic or typical liver function test patterns.