Liver function tests

Dr. Asfia khan

 FUNCTIONS OF LIVER
1. Synthetic function
a. Synthesis of plasma proteins (albumin,
coagulation factors, many globulins)
b. Synthesis of cholesterol
c. Synthesis of triacylglycerol
d. Lipoprotein synthesis
e. Acute phase proteins
2. Metabolic function
a. Carbohydrates: Glycolysis, glycogen
metabolism
b. Ketogenesis, fatty acid synthesis and
breakdown
c. Protein catabolism
3. Detoxification and excretion
a. Ammonia to urea
b. Bilirubin (bile pigment)
c. Drug metabolites
5. Storage function:
Vitamin A, D, E, K and B12
6. Production of bile salts:
Help in digestion
Some example of liver dysfunction
• Hepatocellular disease
• Cholestasis (obstruction of bile flow)
• Cirrhosis
• Hepatitis
• Liver cancer
• Steatosis (fatty liver)
• Genetic Disorders
• Hemochromatosis (iron storage)
Major Clinical Manifestations of Liver Dysfunction
• Jaundice
• Portal hypertension
• Ascites
 When to do LFT ?
1. Jaundice
2. Suspected liver metastasis
3. Alcoholic liver disease
4. Any undiagnosed chronic illness
5. Annual check up of diabetic patients
6. Coagulation disorders
7. Therapy with statins and other drugs to check
hepatotoxicity
 CLASSIFICATION OF THE TESTS ON THE
BASIS OF LIVER FUNCTIONS
Group I (Tests of hepatic excretory function)
i. Serum: Bilirubin; total, conjugated, and unconjugated
ii. Urine: Bile pigments, bile salts and urobilinogen(UBG)

Group II: Liver enzyme panel

 Alanine aminotransferase (ALT) (Marker of liver injury)
 Aspartate aminotransferase (AST) (Marker of liver injury)
 Alkaline phosphatase (ALP) (Marker of cholestasis)
 Gamma glutamyl transferase (GGT) (Marker of
cholestasis)
Group III: Plasma proteins (Tests for synthetic
function of liver)
 Total proteins
 Serum albumin, globulins, A/G ratio
 Prothrombin time
 Blood ammonia
Group IV: Special tests
 Alpha-1 antitrypsin (AAT)
 Ceruloplasmin
 Haptoglobin
 Alpha-2 microglobulin
 Transferrin
 Alpha fetoprotein (AFP)
 Fibrinogen
 C-reactive protein
 CLASSIFICATION OF THE TESTS ON THE
BASIS OF LIVER PATHOLOGY
Group I: Markers of liver dysfunction
• Serum bilirubin: total, conjugated and
unconjugted
• Urine: Bile pigments, bile salts and UBG
• Total protein, serum albumin and A/G ratio
• Prothrombin time
• Blood ammonia
Group II: Markers of hepatocellular injury
• Alanine amino transferase (ALT)
• Aspartate amino transferase (AST)

Group III: Markers of cholestasis

• Alkaline phosphatase
• Gamma glutamyl transferase
• 5’ Nucleotidase
 SERUM BILIRUBIN
• Bilirubin is estimated by van den Bergh reaction,
where diazotised sulfanilic acid reacts with bilirubin to
form a purple-colored complex, azobilirubin.
• Normal serum bilirubin level varies from 0.2 to 0.8
mg/dl.
• The unconjugated bilirubin (free bilirubin or indirect
bilirubin or water insoluble bilirubin) varies from 0.2–
0.7 mg/dl.
• The conjugated bilirubin (direct bilirubin or water
soluble bilirubin) varies from 0.1 – 0.4 mg/dl.
• When bilirubin is conjugated, the purple color
is produced immediately on mixing with the
reagent, the response is said to be van den
Bergh direct positive.

• When the bilirubin is unconjugated, the color

is obtained only when alcohol is added, and
this response is known as indirect positive.
• If both conjugated and unconjugated
bilirubins are present in increased amounts, a
purple color is produced immediately and the
color is intensified on adding alcohol.
• Then the reaction is called biphasic.
Pattern of serum bilirubin variation in
different types of jaundice
 Urinary and fecal findings in different
types of jaundice

Urine Urobilinoge +++ Very low absent

ns (Ehrlich
test)
Feces Stercobilin +++ very low Absent
(clay
coloured
stool)
Causes of jaundice
 Plasma proteins
• All plasma proteins except immunoglobulins
are synthesized by the liver.
• Serum albumin is quantitatively the most
important protein synthesized by the liver, and
reflects the extent of functioning liver cell
mass.
• Since albumin has a fairly long half-life of 20
days, in all chronic diseases of the liver, the
albumin level is decreased.
• Alpha and beta globulins synthesized mainly
by hepatocytes.
• Gamma globulins (Immunoglobulins) are
produced by B lymphocytes (plasma cells).
• Gamma globulins increased in chronic liver
diseases (chronic active hepatitis, cirrhosis
etc.)
• A reversal in A/G ratio is often the rule in
cirrhosis, due to hypoalbuminemia and
associated hypergammaglobulinemia.
• Normal albumin level in blood is 3.5 to 5 g/dl
and globulin level is 2.5 to 3.5 g/dl.
• The turn-over rates of haptoglobin and
transferrin are lesser than albumin. So, they
are useful to identify the recent changes in
liver functions.
 ENZYMES
• The enzymes used in the assessment of
hepatobiliary disease may be divided into two
groups:
(a) Those indicating hepatocellular damage and
(b) Those indicating cholestasis (obstruction).
 ALT and AST
• Normal range of serum ALT : 10-35 IU/L.
• Normal range of serum AST : 5 – 40 IU/L
• The levels of amino transferases (ALT and AST)
in serum are elevated in all liver diseases.
• Very high levels (more than 1000 units) are
seen in acute hepatitis (viral and toxic).
• The degree of elevation may reflect the extent
of hepatocellular necrosis.
• Lowering of the level of transaminases
indicates recovery, but a sudden fall from a very
high level may indicate poor prognosis.
• Elevation of ALT is more in cases of hepatic
disease compared to AST.
• AST > ALT in alcoholic liver disease.
• In alcoholic liver disease, the actual values
show only mild elevation, but a ratio of AST/ALT
more than 2 is quite suggestive.
• Moderate elevation of amino transferases
often between 100-300 U/L is seen in
alcoholic hepatitis, autoimmune hepatitis, and
nonalcoholic chronic hepatitis.
• Minor elevation less than 100U/L is seen in
chronic viral hepatitis (hepatitis C), fatty liver
and in nonalcoholic steatohepatitis (NASH).
 Normal AST: ALT ratio is 0.8.
 A ratio >2 is seen in:
• Alcoholic hepatitis
• Hepatitis with cirrhosis
• Nonalcoholic steatohepatitis (NASH)
• Liver metastases
• Myocardial infarction
• Erythromycin treatment

 ALT higher than AST is seen in:

• Acute hepatocellular injury
• Toxic exposure
• Extrahepatic obstruction (cholestasis)
 Alkaline Phosphatase (ALP)

• Normal range of ALP: 44 to 147 IU/L.

• Very high levels of alkaline phosphatase (ALP)
are noticed in patients with cholestasis or
hepatic carcinoma.
• The bile duct obstruction induces the release
of the enzyme by biliary tract epithelial cells.
• In parenchymal diseases of the liver, mild
elevation of ALP is noticed.
• In hepatitis, inflammatory edema produces an
obstructive phase, during which ALP level is
elevated.
• Very high levels of ALP (10-12 times of upper
limit) may be noticed in extrahepatic
obstruction (obstructive jaundice) caused by
gallstones or by pressure on bile duct by
carcinoma of head of pancreas.
• Intrahepatic cholestasis may be caused by due
to virus (infective hepatitis) or by some drugs.
• ALP is produced by epithelial cells of biliary
canaliculi and obstruction of bile with
consequent irritation of epithelial cells leads
to secretion of ALP into serum.
• Drastically high levels of ALP (10-25 times of
upper limit) are seen in bone diseases where
osteoblastic activity is enhanced.
• Paget's disease
• Rickets
• Osteomalacia
• Osteoblastoma
• Metastatic carcinoma of bone, etc.
 GGT(Gamma glutamyl transferase)

• GGT level in alcoholic liver disease roughly

parallels the alcohol intake.
• Highly sensitive to detecting alcohol abuse.
• Elevated levels of GGT are seen in chronic
alcoholism, pancreatic disease, myocardial
infarction, renal failure, chronic obstructive
pulmonary disease and in diabetes mellitus.
• In liver diseases, GGT elevation parallels that of
ALP and is very sensitive of biliary tract disease.
 5’ Nucleotidase (NTP)

• This is an enzyme made only in the liver.

• The 5'-nucleotidase level is high in diseases
that cause problems with the flow of bile
(cholestasis).
 Prothrombin Time (PT)
• The PT/INR (Prothrombin Time/International
Normalized Ratio) test reflects the liver's ability
to produce clotting factors.
• Half-life: 6 hrs. (indicates the present function of
the liver).
• Normal value: 10-15 sec (expressed in INR).
• A prolonged PT/INR, meaning a higher INR value,
suggests the liver is not producing these factors
properly, potentially indicating liver dysfunction.
• Vitamin K deficiency also causes prolonged PT.
• Intake of vitamin K does not affect PT in liver
disease.
 Blood Ammonia
• Ammonia is highly toxic.
• The normal range is 11 to 32 µmol/L.
• Normal value ranges may vary slightly among
different laboratories.
• Blood ammonia levels are usually less than 50
micromoles per liter (micromol /L), but this
can vary depending on age.
• An increase to only 100 micromol /L can lead
to changes in consciousness.
• A blood ammonia level of 200 micromol /L is
associated with coma and convulsions.