Liver Function T ests (LFT s)

Liver Function Tests (LFT s)

• Noninvasive methods for screening of liver dysfunction
• Help in identifying general types of disorder
• Assess severity and allow prediction of outcome
• Disease and treatment follow up
 LFTS
The conventional liver function test (LFT) consists of
determination of serum/plasma levels of bilirubin and other
liver enzymes.
These include alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP) and
gamma-glutamyltransferase (GGT).
The breakdown of hepatocytes results in the release of
aminotransferases (also referred to as transaminases) such as
ALT (alanine aminotransferase) and AST(aspartate
aminotransferase) into the blood.
Serum/plasma concentrations of total protein and albumin are
useful in assessing liver function.
 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 examples of liver dysfunction
• Hepatocellular disease
• Cholestasis (obstruction of bile flow
• Cirrhosis
• Hepatitis
• Jaundice
• Liver cancer
• Steatosis (fatty liver)
• Genetic Disorders
• Hemochromatosis (iron storage)
 Liver Function T est Used to ……
Detect the presence of liver disease
Distinguish among different types of liver disorders
Gauge the extent of known liver damage
Follow the response to treatment
 Liver Function Tests (LFTs)
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 LFTs
Group II: Markers of hepatocellular injury

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)
 Classification of LFTs
Group III: Markers of cholestasis

Alkaline phosphatase (ALP)

ϒ-glutamyltransferase (GGT)
 Limitations of LFTs
• 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
 Serum Albumin
• The most abundant protein synthesized by the liver
• Normal serum levels: 3.5 – 5 g/dL
• Synthesis depends on the extent of functioning liver cell mass
• Longer half-life: 20 days
• Its levels decrease in all chronic liver diseases.
 In acute liver disease both total protein and serum albumin
concentrations are unaltered.
 In chronic liver disease total protein may be low or high.
 If total protein is high it is most likely due to polyclonal
hypergammaglobulinemia.
 Serum Globulin
• Normal serum levels: 2.5 – 3.5g/dL
•  and -globulins mainly synthesized by the liver
• They constitute immunoglobulins (antibodies)
• High serum -globulins are observed in chronic hepatitis and
cirrhosis:
• IgG in autoimmune hepatitis
• IgA in alcoholic liver disease
 Prothrombin Time (PT)
• Prothrombin: synthesized by the liver, a marker of liver function
• Half-life: 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
 Clotting factors, with the exception of Factor VIII, are produced in
the liver.
 Factor VII is one of the factors involved in the extrinsic pathway and
has the shortest half-life among all clotting factors (4-6 hours).
 Therefore, within a short period after significant liver dysfunction,
PT is prolonged and the magnitude of prolongation is correlated with
the severity of liver dysfunction.
 Aspartate aminotransferase (AST)
• Normal range: 8 – 20 U/L
• AST is primarily a mitochondrial enzyme that is also found in the
heart, muscle, kidney, and brain.
• A marker of hepatocellular damage
• High serum levels are observed in:
Chronic hepatitis, cirrhosis and liver cancer
In acute liver injury, AST levels are higher than ALT;
however, after 24-48 hours ALT levels should be higher than
AST.
 Alanine aminotransferase (ALT)
• ALT is a cytosol enzyme and is more specific for liver disease
than AST
• Normal range (U/L):
Male: 13-35
Female: 10-30
High serum levels in acute hepatitis (300- 1000U/L)
Moderate elevation in alcoholic hepatitis (100- 300U/L)
Minor elevation in cirrhosis, hepatitis C and non-alcoholic
steatohepatitis (NASH) (50- 100U/L)
 Alanine aminotransferase (ALT)
• 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
• ALT has a longer half-life than AST
 Alkaline phosphatase (ALP)
• A non-specific marker of liver disease
 Alkaline phosphatase (ALP) is found in liver, bone, intestine, and
placenta.
 ALP is located in the canalicular and sinusoidal membrane of the
liver
• Normal range: 40 – 125 U/L
• Moderate elevation observed in: Infective hepatitis, alcoholic
hepatitis and hepatocellular carcinoma
 Alkaline phosphatase (ALP)
• High levels are observed in:
 Extrahepatic obstruction (obstructive jaundice) and
intrahepatic cholestasis
• Very high levels are observed in:
Bone diseases
Production of ALP is increased during cholestasis
(intrahepatic or extrahepatic), which results in elevated
activity of ALP in serum;
If ALP level is raised, then the next question is whether the
source of this enzyme is the liver or not.
 Alkaline phosphatase (ALP)
In cholestasis ALP and GGT levels are raised indicating that
the liver is the source of ALP.
If ALP activity is increased but activity of GGT is normal,
then it is unlikely that the liver is the source of excess ALP.
In children showing only elevated ALP, it is most likely related
to osteoblastic activity in their growing bones.
In elevated ALP with normal bilirubin, ALT and AST may be
seen in patients with hepatic metastasis or bone metastasis.
 -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 to detecting alcohol abuse
GGT is a well-established marker for alcohol abuse.
 A normal liver function test (except elevated GGT) is a
characteristic of excessive alcohol intake.
Measurement of gamma-glutamyl trans-peptidase (GGT) levels
can be used to determine if the source of ALP is the liver or not
because GGT is solely produced by the biliary epithelium.
GGT is a microsomal enzyme.
 BILIRUBIN METABOLISM
In the first step of bilirubin synthesis, the heme molecule is
stripped from the hemoglobin molecule.
Heme then passes through various processes
of porphyrin catabolism, which varies according to the region
of the body in which the breakdown occurs.
 The production of biliverdin from heme is the first major step
in the catabolic pathway, after which the enzyme biliverdin
reductase performs the second step, producing bilirubin from
biliverdin.
Ultimately, bilirubin is broken down within the body, and
its metabolites excreted through bile and urine elevated levels
may indicate certain diseases.
It is responsible for the yellow color of healing bruises and
the yellow discoloration in jaundice.
Its breakdown products, such as stercobilin, cause the brown
color of feces.
A different breakdown product, urobilin, is the main
component of the straw-yellow color in urine.
In the liver, bilirubin is conjugated with glucuronic acid by
the enzyme glucuronyltransferase, first to bilirubin
glucuronide and then to bilirubin diglucuronide, making it
soluble in water
The conjugated version is the main form of bilirubin present
in the "direct" bilirubin fraction.
Much of it goes into the bile and thus out into the small
intestine. Though most bile acid is reabsorbed in the terminal
ileum to participate in enterohepatic circulation, conjugated
bilirubin is not absorbed and instead passes into the colon.
There, colonic bacteria deconjugate and metabolize the
bilirubin into colorless urobilinogen, which can be oxidized to
form urobilin and stercobilin.
Urobilin is excreted by the kidneys to give urine its yellow
color and stercobilin is excreted in the feces giving stool its
characteristic brown color.
A trace (~1%) of the urobilinogen is reabsorbed into
the enterohepatic circulation to be re-excreted in the bile.
 Bilirubin
• A by product of red blood cell breakdown

• It is the yellowish pigment observed in jaundice

• High bilirubin levels are observed in:

 Gallstones, acute and chronic hepatitis

 Bilirubin
In hemolytic anemia, indirect bilirubin concentration may be
increased.
Defects in the uptake of unconjugated bilirubin by
hepatocytes may also increase the concentration of
unconjugated bilirubin (indirect bilirubin) in serum.
An increased concentration of conjugated bilirubin (direct
bilirubin) is seen in cholestatic jaundice.
Most of the normal bilirubin found in serum or plasma is
unconjugated (indirect bilirubin).
 Serum bilirubin levels
• Normal
0.2 – 0.8 mg/dL
• Unconjugated (indirect):
0.2 – 0.7 mg/dL
• Conjugated (direct):
0.1 – 0.4 mg/dL
Latent jaundice: Above 1 mg/dL
Jaundice: Above 2 mg/dL
Bilirubin levels and jaundice
Class of Jaundice Causes

Pre-hepatic or hemolytic Abnormal red cells; antibodies; drugs

and toxins; thalessemia
Hemoglobinopathies, Gilbert’s,
Crigler-Najjar syndrome

Hepatic or Hepatocellular Viral hepatitis, toxic hepatitis,

intrahepatic cholestasis

Post-hepatic Extrahepatic cholestasis; gallstones;

tumors of the bile duct, carcinoma of
pancreas
 Summary
Key points regarding interpretation of liver function tests
include:
In acute liver disease without cholestasis, levels of ALT and
AST are significantly elevated and ALP is raised, but usually
less than three times the upper limit of the normal value.
Therefore, ALT and AST levels exceeding 500 U/L are a
common finding in acute liver disease.
In acute cholestasis, ALT and AST are raised but levels are not
very high.
ALP is usually more than three times the upper limit of the
normal value with a parallel increase in GGT levels.
Thank you very much for
your attention