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The Liver Function Tests

Total Protein

Difficult to interpret without knowledge of albumin and globulin fraction

Increased

  • Chronic infection
  • Liver diseases
  • Collagen – Autoimmune diseases
  • Hypersensitivity states
  • Sarcoidosis
  • Cryoglobulinemia
  • Monoclonal gammopathies
  • Heavy chain disease
  • Dehydration
  • Hemolysis

Decreased

  • Decreased Albumin
    • Subacute and chronic debilitating diseases
    • Liver disease
    • Renal disease
    • Nephrotic syndrome
    • Malabsorption and Malnutrition
    • Third degree burns
    • Gastrointestinal loss
    • Exfoliative dermatitis
    • Dilution by IV fluids
  • Hypo- and Agammaglobulinemia
  • Pregnancy

Albumin

An indicator of protein synthesis
Albumin has a long half-life (14-20 days)
May also be lowered by malnutrition or GI or renal losses

Decreased States

  • Subacute and chronic debilitating diseases
  • Liver disease
  • Renal disease
  • Nephrotic syndrome
  • Malabsorption and Malnutrition
  • Third degree burns
  • Gastrointestinal loss
  • Exfoliative dermatitis
  • Dilution by IV fluids

Increased

  • Dehydration

Globulins

 

A/G Ratio

The A/G ratio is associated with protein level. It is the ratio of albumin to globulins. Serum proteins are generally 50-60% albumin, and also include globulins, and other proteins. A normal A/G ratio is around 1.1 to 1.8. A ratio of 2.2 is not unusual with some health conditions.

A low A/G ratio may be due to overproduction of gamma-globulin (monoclonal/polyclonal gammopathy,  multiple myeloma or autoimmune diseases etc.) or due to low albumin (low production as  in cirrhosis or excessive loss as in  nephrotic syndrome or protein losing enteropathy etc.).In contrast, if the A/G ratio is high then one should look for diseases with low gamma-globulin production such as agammaglobuminemia.  Often a serum electrophoresis or immunoelectrophoresis can determine a more specific abnormality.

Total Bilirubin

Reflects a balance between bilirubin production (death of red blood cels or ineffective erythropoiesis) and its conjugation and excretion into bile by the liver.

Total bilirubin = Direct bilirubin + Indirect bilirubin
Elevated direct bilirubin indicated hepatobiliary cause

Increased States

  • Cholestasis: Intrahepatic and Extrahepatic
  • Liver disease
  • Congenital Hyperbilirubinemia
    • Crigler-Najjar
    • Dubin-Johnson
    • Gilbert’s Syndrome
  • Hemolytic anemia
  • Reabsorbing extravasated blood
  • Malnutrition
  • Infection – subacute and chronic
  • Hyperthyroidism
  • Other (increased with exercise, estrogens, OCPs, menstruation, hemolysis, fasting)

Bilirubin, Direct (conjugated, soluble)

Most sensitive test for liver disease

Direct bilirubin is bilirubin conjugated with glucuronic acid at the SER of hepatocytes.

Elevated States

  • Hepatocellular disease
  • Biliary tract obstruction, extrahepatic or intrahepatic
  • Dubin-Johnson syndrome
  • Rotor’s syndrome
  • Hepatic storage syndrome

 

Aspartate aminotransferase (AST/SGOT)

Enzyme that catalyzes the carbohydrate-amino acid interconversion
Alpha-ketoglutarate + aspartate <-> glutamate + Oxalacetate

More sensitive but less specific than ALT for liver disease.

Elevated States:

  • Liver disease
    • Hepatitis
    • Cholestasis, intrahepatic and extrahepatic
    • Alcoholism
    • Drug toxicity
    • Infectious Mononucleosis
    • Metastatic Carcinoma
  • Heart disease
    • Acute myocardial infarction
    • Acute myocarditis
  • Skeletal muscle
    • Skeletal muscle disease
    • Trauma
  • Hematologic
    • Hemolytic anemia
    • Megaloblastic anemia
  • Medications
    • Antibiotics (cipro, nitrofurantoin, ketoconazole, fluconazole, INH)
    • Antiepileptics (phenytoin, carbamazepine)
    • Statins
    • NSAIDs
    • Heparin
    • Glipizide
    • Substances of abuse
  • Other
    • Shock, acute pancreatitis, CHF, ARF, acute pulmonary infarction, tissue necrosis, third degree burns, seizures, eclampsia, heparin therapy

Alanine aminotransferase (ALT)

Intracellular enzymes released by injury or death of hepatic cells
Sensitive but nonspecific test of liver damage

Elevated States

  • Hepatic
    • Alcohol abuse
    • Medications
    • Chronic hepatitis B and C
    • Steatosis and NASH
    • Autoimmune hepatitis
    • Hemochromatosis
    • Wilson’s disease
    • Alpha-1-antitrypsin deficiency
  • Nonhepatic (AST > ALT)
    • Celiac sprue
    • Inherited disorders of muscle metabolism
    • Acquired muscle disease
    • Strenuous exercise

AST/ALT Ratio

Disease

AST/ALT Ratio

Alcoholic liver disease

2.0 -> 6.0

Organic toxic hepatitis

>2.0

Cirrhosis

1.4-2.0

Intrahepatic Cholestasis

>1.5

Extrahepatic Cholestasis

<1.4

Chronic active hepatitis

1.3

Extrahepatic biliary obstruction

0.8

Acute viral hepatitis

0.5-0.8

Alkaline Phosphatase

Used to evaluate liver or bone disfunction.

Elevated alkaline phosphatase

  • Liver
    • Cholestasis: intrahepatic and extrahepatic
    • Liver disease
    • Congestive heart failure
    • Infectious mononucleosis
    • Malignancy with liver metastasis
    • Acute pancreatitis
    • Cytomegalovirus
  • Bone
    • Paget’s disease
    • Secondary hypothyroidism
      • Renal disease
      • Osteomalacia
      • Malabsorption
  • Non-liver, non-bone
    • Pregnancy
    • Sarcoidosis
    • Gyn malignancies
    • Amyloidosis
    • Ulcerative colitis
    • Perforation of bowel
    • Pulmonary and MI
    • Sepsis
    • Benign transiet hyperphosphatasemia

Causes of isolated alkaline phosphatase secondary to liver disease

  • Infiltrative disease
    • TB
    • Lymphoma

Gamma Glutamyl Transferase (GGT)

Used to differentiate the source of an elevated serum alkaline phosphatase (liver or bone). GGT is present in liver but not bone.
Also used to evaluate alcohol abuse.

Elevated GGT

  • Alcoholism
  • Liver disease
  • Obstructive jaundice
  • Metastatic liver disease
  • Congested liver
  • Infectious mononucleosis
  • Pancreatic disease
  • Diabetes mellitus
  • Myocardial infarction
  • Congestive heart failure
  • Neurologic disorders
  • Trauma
  • Nephrotic syndrome
  • Chronic renal failure (occasionally)
  • Sepsis
  • Drugs

Interpretation of Alkaline phosphatase with GGT

Alk Phos

GGT

Source

High

High

Liver

High

Low

Bone

 

Prothrombin Time

An indicator of protein synthesis
A useful daily marker of hepatic function because factors II and VII have half-lives of hours and must be replenished constantly.
May also be elevated if there is a vitamin K deficiency.

Patterns

Pancreatitis

Amylase 3x normal
Amylase 3x normal + ALT 3x normal = biliary pancreatitis

Infiltrative Liver Disease

Isolated elevated ALK

Alcoholic Hepatitis

AST:ALT > 2

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