Liver
Function
Tests
Major Metabolic Functions
of the Liver
Synthetic Function
• Plasma proteins (albumin, globulins), cholesterol, triglycerides and
lipoproteins
Detoxification and excretion
• Ammonia to urea (urea cycle), bilirubin, cholesterol, drug metabolites
Storage Function
• Vitamins A, D, E, K and B12
Production of bile salts
• Helps in digestion
Some example of liver dysfunction
Cholestasis
Hepatocellular
(obstruction of Cirrhosis
disease
bile flow)
Hepatitis Jaundice Liver cancer
Genetic
Steatosis (fatty Disorders
liver)
• Hemochromatosis
(iron storage)
Liver Function Tests
• Noninvasive methods for screening of liver
dysfunction
• Help in identifying general type of disorder
• Assess severity and allow prediction of outcome
• Disease and treatment follow up
Liver Function Test
• Broadly classified as
1.Tests to detect hepatic injury:
• mild or severe; acute or chronic
• Nature of liver injury (hepatocellular or
cholestasis)
2.Tests to assess hepatic function
Classification of LFTs
Group I: Markers of liver dysfunction
▫ Serum bilirubin: total and conjugated
▫ Urine: bile salts and urobilinogen
▫ Total protein, serum albumin and
albumin/globulin ratio
▫ Prothrombin Time
Classification of LFT contd..
Group II: Markers of hepatocellular injury
▫ Alanine aminotransferase (ALT)
▫ Aspartate aminotransferase (AST)
Classification of LFT contd..
Group III: Markers of cholestasis
I. Alkaline phosphatase (ALP)
II. γ- glutamyl transferase (GGT)
Limitations of LFT
• Normal LFT values do not always indicate absence of liver disease
• Liver has very large reserve capacity
• Asymptomatic people may have abnormal LFT results
• Diagnosis should be based on clinical examination
Common serum liver chemistry tests
Bilirubin
• A byproduct of red blood cell breakdown
• It is the yellowish pigment observed in jaundice
• High bilirubin levels are observed in gallstones, acute and chronic
hepatitis
Serum bilirubin levels
• Normal
• 0.2 to 0.8 mg/dL
• Unconjugated/free/indirect (bilirubin-albumin complex)
• 0.2 to 0.7 mg/dL
• Conjugated/direct:
• 0.1 to 0.4 mg/dL
• Latent jaundice:
• Above 1 mg/dL
• Jaundice:
• Above 2 mg/dL
Bilirubin levels and jaundice
Class of Type of Causes
Jaundice Bilirubin
raised
Pre-hepatic or Unconjugated Abnormal red
hemolytic cells; antibodies;
drugs and toxins;
thalessemia
Hemoglobinopat
hies
Hepatic or Unconjugated Viral hepatitis,
Hepatocellular and conjugated toxic hepatitis,
intrahepatic
cholestasis,
Gilbert’s, Crigler-
Naajjar
syndrome
Urinary urobilinogen(UBG) and
urine bile salts
• Most UBG is metabolized in the large intestine, a fraction is
excreted in urine (less than 4 mg/day)
• Normally bile salts are NOT present in urine
• Obstruction in the biliary passages causes leakage of bile salts
into circulation leading to its excretion in urine
Serum Albumin
• The most abundant protein synthesized by the liver
• Normal serum levels: 3.5 to 5g/dL
• Its synthesis depends on the extent of functioning liver cell mass
• Longer half-life of 20 days
• Its levels decrease in all chronic liver diseases
Serum Globulin
• Normal serum levels: 2.5 to 3.5g/dL
• They constitute Igs produced by B lymphocytes as well as alpha
and beta globulins synthesized mainly by hepatocytes
• High serum -globulins are observed in chronic hepatitis and
cirrhosis:
• IgG in autoimmune hepatitis
• IgA in alcoholic liver disease
Albumin to globulin (A/G) ratio
• Normal A/G ratio: 1.2/1 – 1.5/1
• Globulin levels increase in hypoalbuminemia as a compensation
Prothrombin Time (PT)
• Prothrombin: synthesized by the liver, a
marker of liver function
• Its half-life is 6 hrs. (indicates the present
function of the liver)
• PT is prolonged only when liver loses
more than 80% of its reserve capacity
• Vitamin K deficiency also causes
prolonged PT
• Dosage of vitamin K does not affect PT in
liver disease
Aspartate aminotransferase (AST)
• Normal range: 8 – 20 U/L
• A marker of hepatocellular damage
• High serum levels are observed in chronic hepatitis, cirrhosis and
liver cancer
Alanine aminotransferase (ALT)
• More liver-specific than AST
• Normal range (U/L):
• Male: 13-35
• Female: 10-30
• High serum levels are observed in acute hepatitis
(300-1000U/L)
• Moderate elevation is observed in alcoholic
hepatitis (100-300U/L)
• Minor elevation is observed in cirrhosis, hepatitis
C and non-alcoholic steatohepatitis (NASH) (50-
100U/L)
Alanine aminotransferase (ALT)
contd…
• Appears in plasma many days before clinical signs appear
• A normal value does not always indicate absence of liver damage
• Obese but otherwise normal individuals may have elevated ALT
levels
Alkaline phosphatase (ALP)
• A non-specific marker of liver disease
• Produced by bone osteoblasts (for bone calcification)
• Normal range: 40 – 125 U/L
• Modearte elevation observed in:
• Infective hepatitis, alcoholic hepatitis and hepatocellular
carcinoma
Alkaline phosphatase (ALP) contd..
• High levels are observed in:
• Extrahepatic obstruction (obstructive jaundice) and
intrahepatic cholestasis
• Very high levels are observed in:
• Bone diseases
-glutamyltransferase (GGT)
• Used for glutathione synthesis
• Normal range: 10 – 30U/L
• Moderate elevation observed in:
• Infective hepatitis and prostate cancers
• GGT is increased in alcoholics despite normal liver function tests
• Highly sensitive in detecting alcohol abuse
References
• Lippincott’s Illustrated Reviews of Biochemistry
• Clinical Chemistry by Bishop and Fody
