Liver Function Tests

(Gastroenterology. 2002;123:1364-1384; Clin Chem 2000;12:1-60) Adapted, in part, from Pocket Medicine 2nd ed. 2004. Lippincott Wilkins & Williams

TESTS OF HEPATIC FUNCTION:

Albumin: general marker for liver protein synthesis, ↓ slowly in liver failure (T½ ˜20d); A rapid ↓ can occur in the setting of sepsis
Prothrombin Time (PT): depends on synthesis of coagulation factors that are Vitamin K dependant
- An abnormal PT from liver dysfunction occurs in the setting of inadequate Vit K (Normally Vit K po/IV normalizes PT in ˜ 48 hrs)
- Because T½ of some factors (i.e., V, VII) is short, ↑ PT can occur within hours of liver dysfunction
- Factor 8 (only factor synthesized in vascular endothelium, not in liver): Therefore it is normal in FHF! Consumed/Low in DIC!
Bilirubin: product of heme metabolism in liver via hepatocyte, not bile duct cells; unconjugated (indirect) or conjugated (direct – water soluble)

ABNORMAL LIVER TESTS:

Aminotransferases

(ALT [SGPT], AST [SGOT]): intracellular enzymes released 2° necrosis or inflammation (i.e. injury)
- ALT relatively specific for liver
- AST found in liver, heart, skeletal muscle, kidney, and brain
- ALT > AST » viral hepatitis or fatty liver/nonalcoholic steatohepatitis (pericirrhotic)
- AST:ALT >2:1 » alcoholic hepatitis (ALT production depends on B6, which is depleted with ETOH, therefore ↓ levels)
- ↑↑↑ LDH » ischemic or toxic hepatitis
- NOTE: ALT/AST lab assay tests don’t indicate the quantity, rather how quickly it causes an enzymatic reaction:
  - Assumption is, the faster the reaction, the more enzyme is present
Alkaline phosphatase (Aφ): enzyme bound in hepatic canicular membrane
- Aφ also found in bone, intestines, placenta (these will have normal GGT)
- Confirm liver origin: ↑ 5′-NT, ↑ GGT (GGT very sensitive for hepatobiliary disease), or heat fractionation (liver: lives, bone: burns)
- ↑ levels seen with biliary obstruction or intrahepatic cholestasis (ie. hepatic infiltration)

PATTERNS OF LIVER INJURY: OVERVIEW (See Detailed explanation of each below)

Hepatocellular: Damage or destruction of liver cells; ↑ aminotransferases, ± ↑ bilirubin or Aφ

Acute: less than 3 months (i.e. HAV, HBV, Meds, ETOH, Ischemia) or Chronic (HCV, HBV, NASH, ETOH, Hemochromatosis, AIH)
↑↑↑ aminotransferases (>3000): toxic hepatitis (i.e. acetaminophen), ischemia, or severe/abnormal viral hepatitis (i.e. herpes)

Cholestasis: Impaired bile transport; ↑↑ Aφ & GGT and ± bilirubin (don’t depend on bili to show cholestasis pattern); ± ↑ aminotransferases

Isolated hyperbilirubinemia: ↑↑ bilirubin, near normal Aφ and aminotransferases Jaundice is a clinical sign seen when bilirubin >2.5 mg/dl (especially sclera); part of either cholestatic pattern or isolated hyperbilirubinemia

Infiltrative: ↑ Aφ, ± ↑ bilirubin or aminotransferases

Hepatocellular Injury: predominantly ↑↑ AST & ALT, ± ↑ Bili & Aφ