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