EVALUATING LIVER FUNCTION TESTS

 

Knowing how to interpret LFT’s is vital on medicine and surgery.  Here are the basics.

 

First get a history.  Symptoms of anorexia, nausea, vomiting, and fever suggest hepatocellular necrosis, as seen in viral hepatitis.  Symptoms of jaundice, pruritus, clay-colored stools, and dark colored urine suggest cholestasis.  Also get a good family, sexual, travel, and social history including alcohol and drug use.

 

Second, confirm each abnormal liver test with its corresponding test, e.g., an elevated AST with an elevated ALT, an elevated AlkP with an elevated GGT, and a decreased albumin with a prolonged PT.

 

Tests of Hepatic Function

1.       Albumin: t½  = 2-3 wk; levels fall with prolonged hepatic dysfunction.

2.       PT: a daily marker of altered hepatic function; more sensitive than albumin in looking at liver dysfunction.  The most common cause of a prolonged PT is dietary vitamin K deficiency.

 

Tests of Cholestatic Disease

1.       Bilirubin: an indicator of hepatic uptake, metabolic and excretory function.  Normally, 70% of the total bilirubin level is indirect, if indirect bilirubin > 80%, it is an unconjugated hyperbilirubinemia, and suggests hemolysis or Gilbert’s syndrome.  If more than 50% of the total bilirubin is direct bilirubin, it is a conjugated hyperbilirubinemia, and suggests hepatocellular dysfunction or cholestasis.  See next page for an approach to the patient with jaundice.

²         Indirect bilirubin: elevated levels caused by overproduction of pigment, decreased uptake, and decreased conjugation, or increased hemolysis.

²         Direct bilirubin: elevated levels caused by impaired excretion and biliary obstruction.

2.       Alkaline phosphatase (AlkP): indicator of intrahepatic cholestasis, biliary obstruction, and liver infiltration; may also be elevated in childhood, pregnancy, bone regeneration, hyperthyroidism, and neoplastic diseases.  If AlkP is markedly elevated in conjunction with a normal/mildly elevated bilirubin, suspect an infiltrative or granulomatous hepatic disease (sarcoidosis, lymphoma, tuberculosis) or primary biliary sclerosis / primary sclerosing cholangitis.

3.       Gamma glutamyltransferase (GGT): elevated levels are used to confirm that elevated AlkP levels are of hepatic or cholestatic origin.

 

Tests of Hepatocellular Damage

1.       AST (SGOT), ALT (SGPT): enzymes released after hepatocellular death; ALT is more specific for liver damage since AST is found in cardiac and skeletal muscle, kidney, and brain tissue.  The most common reasons for elevated transaminase levels are drugs, non-alcoholic steatohepatitis (NASH), hepatitis C, and alcohol use.

²         Hepatic steatosis / NASH: AST:ALT ratio ~ 1:1, mild elevations in levels (not > 4x normal).

²         Alcoholic hepatitis: AST:ALT ratio > 2:1, AST usually not > 250.

²         AST, ALT levels in the low thousands seen in viral and drug-induced (NSAIDs, ACE inhibitors, statins, phenytoin, carbamazepine, isoniazid, sulfonamides, erythromycin, griseofulvin, fluconazole) hepatitis.

²         AST, ALT levels > 10,000 seen in ischemic and herpes hepatitis, acetaminophen overdose.

Other causes of elevated AST/ALT levels include autoimmune hepatitis, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, acquired muscle diseases, and strenuous exercise.

 

References:

Kamath P.  Clinical Approach to the Patient with Abnormal Liver Test Results.  Mayo Clinic Proceedings 1996; 71(11) 1089-1095

Pratt DS, Kaplan MM.  Evaluation of Abnormal Liver-Enzyme Results in Asymptomatic Patients.  NEJM 2000; 342(17) 1266-1271