LIVER FUNCTION TEST

DESCRIPTION
Liver function tests, or LFTs, include tests that are routinely measured in all clinical laboratories.
The liver is the largest and one of the most important organs in the body. As the body's "chemical factory," it
regulates the levels of most of the biomolecules found in the blood, and acts with the kidneys to clear the blood
of drugs and toxic substances. The liver metabolizes these products, alters their chemical structure, makes them
water soluble, and excretes them in bile.
Laboratory tests for total protein, albumin, ammonia, transthyretin, and cholesterol are markers for the synthetic
function of the liver. Tests for cholesterol, bilirubin, ALP, and bile salts are measures of the secretory
(excretory) function of the liver. The enzymes ALT, AST, GGT, LDH, and tests for viruses are markers for
liver injury.
Some liver function tests are used to determine if the liver has been damaged or its function impaired.
Elevations of these markers for liver injury or disease tell the physician that something is wrong with the liver.

REASONS FOR TESTING LIVER.

Liver functions tests are done to ascertain three problems.
 Liver secretory/excretion function
 Liver injury due to drugs, alcohols, toxins, or Viruses.
 Liver malfunction due to blockage of the flow of bile and liver cancers.

A. Parameter to determine liver injury.

The enzymes ALT, AST, GGT, LDH tests for viruses are markers for liver injury.
ALT and bilirubin are the two primary tests used largely to check liver injury.

 Bilirubin. This is measured by two tests, called total and direct bilirubin. The total bilirubin measures
both conjugated and unconjugated bilirubin while direct bilirubin measures only the conjugated bilirubin
fraction in the blood.

 Alanine Aminotransferase (ALT).Is an enzyme that transfers an amino group from the amino acid
alanine to a ketoacid acceptor (oxaloacetate). The enzyme was formerly called serum glutamic pyruvic
transaminase (SGPT) after the products formed by this reaction. Although ALT is present in other
tissues besides liver, its concentration in liver is far greater than any other tissue, and blood levels in
nonhepatic conditions rarely produce levels of a magnitude seen in liver disease. The enzyme is very
sensitive to necrotic or inflammatory liver injury. Consequently, if ALT or direct bilirubin is increased,
then some form of liver disease is likely. If both are normal, then liver disease is unlikely.

These two tests along with others are used to help determine what is wrong. The most useful tests for
this purpose are the liver function enzymes and the ratio of direct to total bilirubin. These tests are used
 to differentiate diseases characterized primarily by hepatocellular damage (necrosis, or cell death) from
those characterized by obstructive damage (cholestasis or blockage of bile flow).

 Aspartate aminotransferase (AST), formerly called serum glutamic oxaloacetic transaminase

(SGOT), is not as specific for liver disease as is ALT, which is increased in myocardial infarction,
pancreatitis, muscle wasting diseases, and many other conditions. However, differentiation of acute and
chronic forms of hepatocellular injury is aided by examining the ratio of ALT to AST, called the DeRitis
ratio. In acute hepatitis, Reye's syndrome, and infectious mononucleosis the ALT predominates.
However, in alcoholic liver disease, chronic hepatitis, and cirrhosis, the AST predominates.

 Alkaline phosphatase. (ALP) is increased in obstructive liver diseases, but it is not specific for the
liver. Increases of a similar magnitude (three- to five-fold normal) are commonly seen in bone diseases,
late pregnancy, leukemia, and some other malignancies. The enzyme gamma-glutamyl transferase
(GGT) is used to help differentiate the source of an elevated ALP. GGT is greatly increased in
obstructive jaundice, alcoholic liver disease, and hepatic cancer. When the increase in GGT is two or
more times greater than the increase in ALP, the source of the ALP is considered to be from the liver.
When the increase in GGT is five or more times the increase in ALP, this points to a diagnosis of
alcoholic hepatitis. GGT, but not AST and ALT, is elevated in the first stages of liver inflammation due
to alcohol consumption, and GGT is useful as a marker for excessive drinking. GGT has been shown to
rise after acute persistent alcohol ingestion and then fall when alcohol is avoided.

 Lactate Dehydrogenase (LDH). This is found in almost all cells in the body. Different forms of the
enzyme (isoenzymes) exist in different tissues, especially in heart, liver, red blood cells, brain, kidney,
and muscles. LDH is increased in megaloblastic and hemolytic anemias, leukemia and lymphomas,
myocardial infarction, infectious mononucleosis, muscle wasting diseases, and both necrotic and
obstructive jaundice. While LDH is not specific for any one disorder, the enzyme is elevated (two to
five-fold normal) along with liver function enzymes in both necrotic and obstructive liver diseases. LDH
is markedly increased in most cases of liver cancer.

B. Excretion/Secretion
Tests for cholesterol, bilirubin, ALP, and bile salts are measures of the secretory (excretory) function of the
liver.

C. Synthetic function
Laboratory tests for total protein, albumin, ammonia, transthyretin, and cholesterol are markers for the synthetic
function of the liver.
Cholesterol is synthesized by the liver, and cholesterol balance is maintained by the liver's ability to remove
cholesterol from lipoproteins, and use it to produce bile acids and salts that it excretes into the bile ducts. In
obstructive jaundice caused by stones, biliary tract scarring, or cancer, the bile cannot be eliminated and
cholesterol and triglycerides may accumulate in the blood as low-density lipoprotein (LDL) cholesterol. In
acute necrotic liver diseases triglycerides may be elevated due to hepatic lipase deficiency. In liver failure
caused by necrosis, the liver's ability to synthesize cholesterol is reduced and blood levels may be low.
Albumin is the protein found in the highest concentration in blood, making up over half of the protein mass.
Albumin has a half-life in blood of about three weeks and decreased levels are not seen in the early stages of
liver disease. A persistently low albumin in liver disease signals reduced synthetic capacity of the liver and is a
sign of progressive liver failure. In the acute stages of liver disease, proteins such as transthyretin (prealbumin)
with a shorter half-life may be measured to give an indication of the severity of the disease

ABNORMAL VALUES EXPLAINED.

ALT: Values are significantly increased in cases of hepatitis, and moderately increased in cirrhosis, liver tumor,
obstructive jaundice, and severe burns. Values are mildly increased in pancreatitis, heart attack, infectious
mononucleosis, and shock. Most useful when compared with ALP levels.
AST: High levels may indicate liver cell damage, hepatitis, heart attack, heart failure, or gall stones.
ALP: Elevated levels occur in diseases that impair bile formation (cholestasis). ALP may also be elevated in
many other liver disorders, as well as some lung cancers (bronchogenic carcinoma) and Hodgkin's lymphoma.
However, elevated ALP levels may also occur in otherwise healthy people, especially among older people.
GGT: Increased levels are diagnostic of hepatitis, cirrhosis, liver tumor or metastasis, as well as injury from
drugs toxic to the liver. GGT levels may increase with alcohol ingestion, heart attack, pancreatitis, infectious
mononucleosis, and Reye's syndrome.
LDH: Elevated LDH is seen with heart attack, kidney disease, hemolysis, viral hepatitis, infectious
mononucleosis, Hodgkin's disease, abdominal and lung cancers, germ cell tumors, progressive muscular
dystrophy, and pulmonary embolism. LDH is not normally elevated in cirrhosis.
Bilirubin: Increased indirect or total bilirubin levels can indicate various serious anemias, including hemolytic
disease of the newborn and transfusion reaction. Increased direct bilirubin levels can be diagnostic of bile duct
obstruction, gallstones, cirrhosis, or hepatitis. It is important to note that if total bilirubin levels in the newborn
reach or exceed critical levels, exchange transfusion is necessary to avoid kernicterus, a condition that causes
brain damage from bilirubin in the brain.
Ammonia: Increased levels are seen in primary liver cell disease, Reye's syndrome, severe heart failure,
hemolytic disease of the newborn, and hepatic encephalopathy.
Albumin: Albumin levels are increased due to dehydration. They are decreased due to a decrease in synthesis
of the protein which is seen in severe liver failure and in conditions such as burns or renal disease that cause
loss of albumin from the blood.