Liver Function Tests

Because of the variety of liver functions, it is not possible to accurately test total liver function, as with the kidney.

However, it is possible to test specific aspects of liver function, specifically hepatocellular function and cholestasis.

Tests of Hepatocellular Function

(1) High Serum Transaminase – test for abundant liver enzymes that are released during necrosis

transaminases transfer NH₂ from glutamate to keto acid, producing a -ketoglutarate and an amino acid

AST (aspartate aminotransferase, a.k.a. SGOT) – produces aspartate from oxaloacetate

if increased: normal in newborns, myocardial infarction, viral hepatitis, or toxic hepatitis

also in heart, muscles, kidneys, and RBC’s – injury to any of these Ý AST, so not specific for liver damage

ALT (alanine aminotransferase, a.k.a. SGPT) – produces alanine from pyruvate

much more in liver than anywhere else, so high levels likely indicate liver damage

serum transaminase levels (normal is <40 I.U./L)

moderate (40-500 I.U./L): chronic hepatitis, drug tox., fatty liver, alcoholic liver disease, autoimmune liver disease

alcoholic liver disease – never above 300 I.U./L, AST > ALT (ALT depleted within hepatocytes)
fatty liver – ALT > AST

high (500-10,000 I.U./L) – viral hepatitis, drug tox., ischemic injury (after hypotension), heat stroke, autoimmunity

(2) High Lactate Dehydrogenase – released during necrosis, but also in heart, bone, kidneys, and RBC’s - not specific

(3) Slow Elimination of Galactose – galactose serum half-life longer if liver damaged (used by liver transplant programs)

(4) Lower Liver Protein Synthesis – serum albumin or clotting factors (represented by prothrombin (PT) time)

albumin – does not drop until liver function is very poor, and even then takes weeks to give positive test(t_1/2 = 20 days)

false positive: many other things can cause albumin levels to fall

malnutrition, protein in urine (proteinurea) or stool (protein-losing enteropathy), exfoliating rash

gamma globulin – most abundant protein after albumin; equal to total protein minus albumin

gamma globulin is elevated in liver damage
gamma globulin is reduced in protein losing enteropathy or exfoliation, and normal in proteinuria

PT time – all clotting factors except Factor VIII made by liver, although major loss required before clotting suffers

fast drop in clotting efficiency during liver damage – Factor VII has a 6 hour half-life
vitamin K is required for Factors II, VII, IX, and X, so vitamin K deficiency will decrease prothrombin time as well

Tests for Cholestasis

Cholestasis is impaired bile secretion and/or flow; regurgitation into plasma of bile components; Ý serum alk. phos, Ý serum cholesterol, pruritis; blunting and loss of canilicular microvilli, canilicular dilation and bile plugs

(1) High Serum Conjugated Bilirubin – hepatocellular function is usually still normal Þ conjugated form released to blood

also high serum cholesterol and bile acids

(2) High Alkaline Phosphatase – made in canilicular membrane – elevated levels during cholestasis

Ý during last trimester, puberty, bone disease, liver disease

also found in bone, liver, kidney, intestine, mammary gland, and placenta – not always specific test

GGTP (gamma glutamyl transpeptidase) – made in close proximity to alk. phos; cholestasis elevates both

5-nucleotidase works the same way; also, bone alkaline phosphatase is heat labile ("bones burn"); neither test commonly used today

What if alkaline phosphatase is elevated and bilirubin is normal? – several possibilities

incomplete biliary obstruction, bone disease, placenta, or infiltrative liver lesions

infiltrative liver lesions: primary/secondary neoplasms; granulomas (sarcoidosis); liver abscesses; rare conditions like amyloidosis; primary biliary cirrhosis (autoimmune)

Some Other Tests

urine urobilinogen – test enterohepatic circulation – if jaundice occurs without urobilinogen Þ total biliary obstruction

alpha fetoprotein (AFP) – very high (>500 ng/ml) in primary hepatocellular carcinoma, also pregnancy

good test to monitor chronic liver disease to test for cancer

iron levels (serum ferritin, serum iron, total iron binding capacity) – test for hemochromatosis (common and treatable)

>500 ng/ml ferritin with >75% iron saturation

antimitochondrial antibody (AMA) – test for primary biliary cirrhosis (autoimmunity to small bile duct)– 90% sensitivity

blood ammonia – raised if liver damaged

tests for conditions that damage the liver:

serum ceruloplasmin–copper binding protein deficient (<20 mg/dl) in Wilson’s disease, which causes cirrhosis

alpha1 antitrypsin deficiency – sytemic effects, causes cirrhosis