Assignment

Topic: Liver Function Test

Submitted To: Sir Raza
Course: Clinical Biochemistry
Course code: Biochem-302
Group # 1
Eman Khan (37)
Areeba Khan (1)
Emaan Nasir (10)
Manahil Hanif (5)
Sadia Mumtaz (22)
Wishma Yasir (2)
Farman Ullah Afridi (52)
________________________________________________________
Department of Human Nutrition and Dietetics, FFSN, BZU,
Multan.
________________________________________________________
Topic: Liver Function Test:
Overview:
Liver function tests (LFTs), also known as liver chemistries, are a group of tests that help
determine the health of your liver by measuring the levels of proteins, liver enzymes, and
bilirubin in your blood. They can also monitor the progression or treatment of an existing
disease.

Depending on the test, either higher- or lower-than-typical levels of these enzymes or

proteins can indicate a problem with your liver. Some of the tests look for enzymes that
you’d find in your blood such as alanine aminotransferase (ALT), aspartate aminotransferase
(AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), 5'nucleotidase, total
bilirubin, conjugated (direct) bilirubin, unconjugated (indirect)bilirubin, prothrombin time
(PT), the international normalized ratio (INR), lactate dehydrogenase, total protein, globulins,
and albumin; only when your liver is damaged or has a disease. Others check that the organ is
working the way it should.

Why Are Liver Function Tests Done? (ETIOLOGY)

Some of the reasons liver function tests may be recommended include:

1- To check for damage from liver infections, such as hepatitis B and hepatitis C,
especially if it’s suspected you were exposed to a virus that causes hepatitis
2- To monitor the side effects of certain medications because some medications are
known to affect the liver, including:
 NSAIDs
 Statins
 Antibiotics
 Antiseizure medications
 Tuberculosis drugs
3- If you already have liver disease, to monitor the disease and how well a particular
treatment is working
4- If you’re experiencing the symptoms of a liver disorder or have a family history of a
liver disease, such as fatty liver disease
5- If you have certain medical conditions, such as:
 high triglycerides
 diabetes
 high blood pressure
 anemia
6- Look for signs of serious disease, particularly scarring of the liver, called cirrhosis.
7- If you drink alcohol frequently
8- If you have gallbladder disease
Certain tests can reflect different aspects of liver function. For example, elevated alanine
transaminase and aspartate transaminase disproportional to bilirubin and alkaline phosphatase
levels often indicate liver disease.

Symptoms To Notice?
Your liver does all kinds of work that’s crucial for your health. It helps break down food,
clean your blood, make proteins, and store energy. If something goes wrong with it, you
might have many symptoms, from yellow skin to slurred speech. That’s when you might need
a liver test. General symptoms of liver problems include:

 Lack of appetite
 Nausea or vomiting
 Weakness or feeling very tired
 Yellowish eyes or skin (jaundice)
 Dark urine or light-colored poop (less common)
 Swelling in your belly (less common)

Often, however, you don’t notice any symptoms.

Types of LFTs and What They Measure:

There are a number of liver tests, with lots of complex names. Some common ones include:

1- Alanine transaminase (ALT) test:

ALT is an enzyme that helps break down proteins by converting protein into energy for
liver cells and is found mainly in your liver.
If the liver is damaged or not functioning properly, ALT can be released into the blood.
This causes ALT levels to increase. A higher result than what’s typical on this test can be
a sign of liver cancer, hepatitis, and cirrhosis.
2- Aspartate aminotransferase (AST) test:
Aspartate aminotransferase (AST) is an enzyme found in several parts of your body,
including your:
 heart
 brain
 pancreas
 liver
 muscles

AST is an enzyme that helps the body break down amino acids.

When the liver is damaged, AST can be released into the bloodstream. A high result on an
AST test might indicate a problem with the liver or muscles. This test is sometimes
referred to as SGOT. Higher than normal results are a sign of:
 steatohepatitis
  cirrhosis
 liver damage due to alcohol consumption
 pancreatitis
 thyroid disease
 mononucleosis
 hepatitis
Since AST levels aren’t as specific of a marker for liver damage as ALT, it’s usually
measured together with ALT to check for liver problems. For example, a high AST: ALT
ratio may indicate alcoholic liver disease.
3- Alkaline phosphatase (ALP) test:
Alkaline phosphatase (ALP) is an enzyme found in your bones, bile ducts, and liver and
is important for breaking down proteins. An ALP test is typically ordered in combination
with several other tests. You might have high levels if you have liver damage or disease, a
blocked bile duct, or bone disease. Higher than normal results are a sign of:
 hepatitis
 cirrhosis
 cholecystitis
 bone disease
 mononucleosis
Lower than normal results are a sign of:
 malnutrition
 heart failure
 certain types of cancer
4- Albumin and total protein test:
 Albumin is one of several proteins made in the liver. Your body needs these
proteins to fight infections and to perform other functions. Lower-than-usual
levels of albumin and total protein may mean liver damage or disease. These low
levels also can be seen in other gastrointestinal and kidney-related conditions.
Higher than normal results are a sign of: dehydration and severe diarrhea

Lower than normal results are a sign of:

 malnutrition
 infection
 cirrhosis
 kidney disease
 thyroid disease
5- Bilirubin test:
Bilirubin is a waste product from the breakdown of red blood cells. It’s ordinarily
processed by the liver. It passes through the liver before being excreted through your
stool.
A damaged liver can’t properly process bilirubin. This leads to an atypically high level of
bilirubin in the blood. At times, conditions such as a blockage of the liver ducts or certain
types of anemia and jaundice also can lead to elevated bilirubin. Higher than normal
results are a sign of:

 compromised liver function, which requires further testing

 mononucleosis
6- Gamma-glutamyltransferase (GGT) Test:
GGT is an enzyme in the blood. Higher-than-usual levels may mean liver or bile duct
damage. This test is nonspecific and may be elevated in conditions other than liver
disease. Higher than normal results are a sign of:

 alcohol use disorder

 hepatitis
 cirrhosis
 liver cancer
 blocked bile duct
 pancreatitis
 diabetes
 heart failure
 mononucleosis
7- Prothrombin time (PT) Test:
This test measures the time it takes your blood to clot. Increased PT may mean liver
damage. However, it also can be higher if you're taking certain blood-thinning drugs,
such as warfarin. You probably won’t have this test until you have had other liver tests.
It’s also called the International Normalized Ratio (INR). Longer than normal results are
a sign of:

 compromised liver function, which requires further tests

 blood clotting disorder
 side effects of blood-thinning medications
 vitamin K deficiency
8- Lactic dehydrogenase (LD) test:
This test can find tissue damage and may assist in the diagnosis of liver disease. Lactic
dehydrogenase is a type of protein (also called an isoenzyme). It is involved in the body's
metabolic process. However, this is a very nonspecific liver test. It is rarely used for liver
disease assessment.

9- 5'-nucleotidase test:
This test measures the levels of 5'- nucleotidase (an enzyme specific to the liver). The 5'-
nucleotidase level is elevated in persons with liver diseases, especially those diseases
 associated with cholestasis. This is disruption in the formation of, or obstruction in the
flow of bile.

How to Prepare for a Liver Function Test:

Certain foods and medicines can affect the results of your liver function tests. Your doctor
will probably ask you to avoid eating food and taking some medicines before your blood is
drawn.

Potential risks of a liver function test:

Blood draws are routine procedures and rarely cause any serious side effects. However, the
risks of giving a blood sample can include:

 bleeding under the skin or hematoma

 excessive bleeding
 fainting
 infection

Prevalence:
Elevated liver function tests are found in approximately 8% of the general population. These
elevations may be transient in patients without symptoms, with up to 30% of elevations
resolving after three weeks. Thus, care should be taken when interpreting these results to
avoid unnecessary testing.

Anatomy of the liver:

The liver is located in the upper right-hand portion of the abdominal cavity, beneath the
diaphragm, and on top of the stomach, right kidney, and intestines.
Shaped like a cone, the liver is a dark reddish-brown organ that weighs about 3 pounds.
There are 2 distinct sources that supply blood to the liver, including the following:
 Oxygenated blood flows in from the hepatic artery
 Nutrient-rich blood flows in from the hepatic portal vein
The liver holds about one pint (13%) of the body's blood supply at any given moment. The
liver consists of 2 main lobes. Both are made up of 8 segments that consist of 1,000 lobules
(small lobes). These lobules are connected to small ducts (tubes) that connect with larger
ducts to form the common hepatic duct. The common hepatic duct transports the bile made
by the liver cells to the gallbladder and duodenum (the first part of the small intestine) via the
common bile duct.
Functions of the liver:
The liver regulates most chemical levels in the blood and excretes a product called bile. This
helps carry away waste products from the liver. All the blood leaving the stomach and
intestines passes through the liver. Thliver processes this blood and breaks down, balances,
and creates the nutrients and also metabolizes drugs into forms that are easier to use for the
rest of the body or that are nontoxic. More than 500 vital functions have been identified with
the liver. Some of the more well-known functions include the following:
 Production of bile, which helps carry away waste and break down fats in the small
intestine during digestion
 Production of certain proteins for blood plasma
 Production of cholesterol and special proteins to help carry fats through the body
 Conversion of excess glucose into glycogen for storage (glycogen can later be
converted back to glucose for energy) and to balance and make glucose as needed
 Regulation of blood levels of amino acids, which form the building blocks of proteins
 Processing of hemoglobin for use of its iron content (the liver stores iron)
 Conversion of poisonous ammonia to urea (urea is an end product of protein
metabolism and is excreted in the urine)
 Clearing the blood of drugs and other
poisonous substances
 Regulating blood clotting
 Resisting infections by making
immune factors and removing
bacteria from the bloodstream
  Clearance of bilirubin, also from red blood cells. If there is an accumulation of
bilirubin, the skin and eyes turn yellow.
When the liver has broken down harmful substances, its by-products are excreted into the bile
or blood. Bile by-products enter the intestine and leave the body in the form of feces. Blood
by-products are filtered out by the kidneys, and leave the body in the form of urine.
Liver disease pathophysiology:
The functions of the liver are wide-ranging and include the synthesis of clotting factors and
metabolism of drugs and bilirubin; symptoms of liver disease related to the liver’s inability to
perform these functions.
Liver disease:
Liver disease is a broad term describing any disease that affects the liver and can be classified
as acute or chronic.
Acute liver disease:
If the onset of symptoms does not exceed six months then a patient is deemed to have acute
liver disease. Most cases are self-limiting episodes of hepatocyte inflammation or damage,
which resolve without causing further complications.
In some rare cases, the damage is so severe that it affects the whole liver leading to acute
liver failure. These cases are associated with high mortality and may require liver
transplantation.
Chronic liver disease:
Patients with symptoms of liver disease that persist for more than six months have chronic
liver disease. It occurs when permanent structural changes within the liver occur secondarily
to longstanding hepatocyte damage.
Stages of chronic liver disease:
Chronic liver disease progresses in roughly four stages:
 Hepatitis.
 Fibrosis.
 Cirrhosis.
 Liver failure.
Stage 1: Hepatitis:
Hepatitis means inflammation in your liver tissues. Inflammation is your liver’s response to
injury or toxicity. It’s an attempt to purge infections and start the healing process. Acute
hepatitis (an immediate and temporary response) often accomplishes this. But when the
injury or toxicity continues, so does the inflammation. Chronic hepatitis causes hyperactive
healing that eventually results in scarring (fibrosis).
Stage 2: Fibrosis:
Fibrosis is a gradual stiffening of your liver as thin bands of scar tissue gradually add up. Scar
tissue reduces blood flow through your liver, which reduces its access to oxygen and
nutrients. This is how your liver’s vitality begins to gradually decline. Remarkably, some
amount of fibrosis is reversible. Your liver cells can regenerate, and scarring can diminish if
the damage slows down enough for it to recover.
Stage 3: Cirrhosis:
Cirrhosis is severe, permanent scarring in your liver. This is the stage where fibrosis is no
longer reversible. When your liver no longer has enough healthy cells left to work with, its
tissues can no longer regenerate. But you can still slow or stop the damage at this stage.
Cirrhosis will begin to affect your liver function, but your body will attempt to compensate
for the loss, so you might not notice at first.
Stage 4: Liver Failure
Liver failure begins when your liver can no longer function adequately for your body’s needs.
This is also called “decompensated cirrhosis” — your body can no longer compensate for the
losses. As liver functions begin to break down, you’ll begin to feel the effects throughout
your body. Chronic liver failure is a gradual process, but it is eventually fatal without a liver
transplant. You need a liver to live.

Components of Liver Function Test:

Hepatocellular Labs:
Aminotransferase includes AST and ALT. They are markers of hepatocellular injury. They
participate in gluconeogenesis by catalyzing the transfer of amino groups from aspartic acid
or alanine to ketoglutaric acid to produce oxaloacetic acid and pyruvic acid, respectively.
AST is present as cytosoli1c and mitochondrial isoenzymes and is found in the liver, cardiac
muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and red cells. It is not as
sensitive or specific for the liver as ALT and elevation in AST may be seen as secondary to
nonhepatic causes as well. AST activity in neonates and infants is approximately twice that in
adults, but these decline to adult levels by approximately six months.
ALT is a cytosolic enzyme that is found in high concentrations in the liver. The half-life of
ALT is approximately 47 ± 10 hours. ALT is usually higher than AST in most types of liver
disease in which the activity of both enzymes is predominantly from the hepatocyte cytosol.
Hepatocellular injury and not necessarily cell death triggers the release of these enzymes into
circulation. Both AST and ALT values are higher in normal males than females.They also
correlate with obesity with a normal reference range higher in those with higher body mass
index.
Cholestasis Labs:
Alkaline phosphatase is part of a family of zinc metalloenzymes that are highly concentrated
in the microvilli of the bile canaliculus as well as several other tissues (e.g., bone, intestines,
and placenta). There are four isozymes: placental ALP or hPLALP (human placental ALP),
germ cell ALP (GCALP or PLALP-like), intestinal ALP (IALP), and tissue-nonspecific ALP
(TNALP). Of these four, PLALP and GCALP are the most heat stable at 65 C, and the bone
ALP component of TnALP is the least. In healthy, non-smoking individuals, the PLALP and
GCALP represent less than 1% of total ALP activity in the serum.
A condition that can result in significantly increased plasma ALP is benign transient
hyperphosphatasemia. Originally described in infants, transient hyperphosphatasemia can
also occur in adults and during pregnancy. There is a marked rise in ALP, often to several
thousand IU/L, which usually indicates significant pathology. It is, however, a benign
condition with a return to normal of the ALP in 6 to 8 weeks. Transient
hyperphosphatasaemia is associated with concurrent infections in over 60% of cases,
particularly GIT infections. There is a characteristic pattern on polyacrylamide gel
electrophoresis, with the normal pattern of isoenzymes being accompanied by variant forms
that react with neuraminidase. It is believed to be due to changes in carbohydrate side chains
causing failure of recognition by receptors and reduced clearance, thus prolonging half-life.
Glycoprotein gamma-glutamyltransferase (GGT) is located on membranes of cells with high
secretory or absorptive activities. Its primary function is to catalyze the transfer of a gamma-
glutamyl group from peptides to other amino acids. It is also abundant in many other sources
of the body (kidney, pancreas, intestine, prostate, testicles, spleen, heart, and brain) but is
more specific for biliary disease when compared to alkaline phosphatase because it is not
present in bone. Serum GGT shows electrophoretic mobility and lectin-affinity reaction
identical to the liver enzyme but different from GGT from the kidney, urine, and
pancreas.GGT levels are reported to be increased by an average of 12-fold in obstructive liver
disease compared to ALP, which increased only 3-fold, so GGT is slightly more sensitive
than ALP in this regard.GGT activity level in children may be a reliable index of bile duct
damage. It is a useful indicator in separating the two forms of idiopathic cholestasis, with or
without bile duct involvement. In infants diagnosed with biliary atresia and managed
surgically, the GGT levels stay high in the blood if the infant is breastfed. This is due to the
high level of GGT in human breast milk for at least four weeks postpartum.
There is a relationship between plasma GGT activity and weight, with values being 50%
higher in individuals with a BMI greater than 30 kg/m2. This is believed to be due to fat
deposition in the liver (steatosis) in obese subjects. Steatosis with a raised plasma GGT also
occurs in diabetes mellitus, non-alcoholic steatohepatitis, and non-alcoholic fatty liver
disease. Any liver disease that results in fibrosis and/or cirrhosis, such as alcoholic cirrhosis,
PBC, PSC, hemochromatosis, α1-antitrypsin deficiency, and Wilson disease, will cause a
raised plasma GGT. Space-occupying lesions, including malignancy (HCC or metastases
secondary to malignancy elsewhere in the body), and granulomatous disease, for example,
sarcoidosis and TB, are also associated with a raised plasma GGT.5′-Nucleotidase (5′NT) is
associated with the canalicular and sinusoidal plasma membranes. Its function is undefined.
5′NT is also found in the intestine, brain, heart, blood vessels, and endocrine pancreas. Serum
levels of 5′NT are unaffected by sex or race, but age affects the level; values are lowest in
children and increase gradually, reaching a plateau at approximately age 50 years. As
with GGT, the primary role of the serum 5′NT level is to identify the organ source of an
isolated serum alkaline phosphatase elevation. The 5′NT level is not increased in bone
disease but primarily in hepatobiliary disease. LDH is commonly included in biochemical
liver panels but has poor diagnostic specificity for liver disease. Markedly increased LDH
levels are observed in hepatocellular necrosis, shock liver, lymphoma,
or hemolysis associated with liver disease.
Bilirubin is the end product of heme catabolism, with 80% derived from hemoglobin.
Unconjugated bilirubin is transported to the liver loosely bound to albumin. Bilirubin
is water-insoluble and cannot be excreted in the urine. Bilirubin that is conjugated is water-
soluble and appears in the urine. It is conjugated in the liver to bilirubin glucuronide and
subsequently secreted into bile and the gut, respectively.

Synthetic Function Tests:

Albumin is synthesized by the hepatic parenchymal cells at a rate dependent on colloidal
osmotic pressure and dietary protein intake. The rate of albumin synthesis is also subject to
feedback regulation determined by the plasma albumin concentration. Maintenance of plasma
albumin concentrations can be achieved with only 10% of normal hepatocyte mass. The half-
life of albumin is 21 days. Traces of albumin can be found in almost all extracellular body
fluids. Little is lost from the body by excretion. It is catabolized in various tissues, which are
taken up by cells by pinocytosis. Its constituent amino acids are released by intracellular
proteolysis and returned to the body pool. With any liver disease, there is a fall in serum
albumin, reflecting decreased synthesis. If liver function is normal and serum albumin is low,
this may reflect poor protein intake (malnutrition) or protein loss (nephrotic syndrome,
malabsorption, or protein-losing enteropathy).
Prothrombin time (PT) measures the rate of conversion of prothrombin to thrombin. Except
for factor VIII, all other coagulation factors are synthesized by the liver. Prothrombin time
requires factors II, V, VII, and X, and, as these are made in the liver, the liver's function is
crucial in coagulation. Suppose the synthetic function of the liver is normal and prothrombin
time is delayed. This may indicate treatment with warfarin, consumptive coagulopathy (eg,
disseminated intravascular coagulopathy), or vitamin K deficiency.

Serological Tests:
Liver-related autoantibodies are crucial for correctly diagnosing and classifying autoimmune
liver diseases, namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary
cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children.AIH-1 is
specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is
specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver
cytosol type 1 (anti-LC1). SMA, ANA, and anti-LKM antibodies can be present in de-novo
AIH following liver transplantation.PBC is specified by antimitochondrial antibodies (AMA)
reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate
dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear
pore gp210 and nuclear body sp100. Sclerosing cholangitis presents in at least two variants;
first, the classical primary sclerosing cholangitis (PSC) mostly affects adult men wherein the
only (and non-specific) reactivity is an atypical perinuclear anti-neutrophil cytoplasmic
antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA)
and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with
serological features resembling those of type 1 AIH.

Secondary Biochemical Liver Tests:

Alpha-fetoprotein (AFP) measurements are used as a tumor marker for the detection and
monitoring of primary hepatocellular malignancies, such as hepatoblastoma and HCC.
Hepatoblasts produce alpha-fetoprotein, which is why it is raised in the regenerating liver,
particularly in chronic viral hepatitis.
Carbohydrate deficient transferrin is a high-specificity test for detecting excess alcohol intake
as a cause of liver damage. The carbohydrate antigen CA19-9 is useful in monitoring the
activity of the autoimmune disease PSC, which often progresses to a tumor of the bile ducts
or cholangiocarcinoma. Measurement of serum ferritin can be useful in identifying
hemochromatosis, but ferritin is a positive acute phase reactant, so it is raised in many
illnesses as well as being released from damaged hepatocytes in acute hepatic failure.

Specimen Collection and Preservation

In liver function tests (LFTs), specimen collection and preservation are crucial steps to
ensure accurate results. Here's a general guideline:

Specimen Collection:
 Blood samples are typically collected for liver function tests. Venous blood drawn
from a vein in the arm is the most common method.
 Before drawing blood, it's important to confirm patient identity and ensure proper
labeling of specimen containers to prevent mix-ups.
 The patient should be properly positioned and relaxed to minimize stress-induced
fluctuations in liver enzyme levels.
 Use sterile techniques to avoid contamination of the sample.
 Collect an adequate volume of blood as per the laboratory's requirements. Usually, a
few milliliters are sufficient for liver function tests.

Preservation:
 Once collected, the blood sample needs proper handling to preserve its integrity until
it reaches the laboratory for analysis.
 Serum or plasma is typically used for liver function tests. To obtain serum, collect
blood in a tube without anticoagulants and allow it to clot. For plasma, use an
anticoagulant such as EDTA or heparin.
 After collection, the sample should be gently mixed to ensure thorough mixing of the
clot activator or anticoagulant with the blood.
 Promptly separate the serum or plasma from the cells by centrifugation. This step
prevents hemolysis (rupture of red blood cells), which can release enzymes and affect
test results.
 Transfer the serum or plasma into properly labeled tubes suitable for storage and
transport. Tubes should be tightly sealed to prevent evaporation or contamination.

If there will be a delay in transporting the samples to the laboratory, store them appropriately.
Typically, samples are refrigerated at 2-8°C if analysis will be delayed beyond a few hours.
However, follow specific instructions provided by the laboratory.
Avoid freezing the samples unless specific test protocols require, as freezing can alter
enzyme activity and affect test results.

Transportation:
 Ensure proper packaging and labeling of samples for transportation to the laboratory.
 Use insulated containers with ice packs or temperature-controlled containers if
samples need to be transported over long distances or in warm climates to maintain
the required temperature.
 Follow any specific transportation instructions provided by the laboratory or testing
facility.
 The serum is the specimen of choice. Consider all plasma or serum specimens
potentially positive for infectious agents, including HIV and the hepatitis B virus.
 All specimens should be handled with standard precautions and sent to the lab
immediately for processing.
 Separated serum or plasma should not remain at +15 C to +30 C longer than 8 hours.
If assays are not completed within 8 hours, serum or plasma should be stored at +2 C
to +8 C. If assays are not completed within 48 hours, or the separated sample is to be
stored beyond 48 hours, samples should be frozen at –15 C to –20 C. Frozen samples
should be thawed only once. Analyte deterioration may occur in samples that are
repeatedly frozen and thawed.

Testing Procedures:
Liver function tests are performed on semi-automatic or fully automated analyzers, which are
based on the principle of photometry. Photometry is the measurement of light absorbed in the
ultraviolet (UV) to visible (VIS) to infrared (IR) range. This measurement is used to
determine the amount of an analyte in a solution or liquid. Photometers utilize a specific light
source and detectors that convert light passed through a sample solution into a proportional
electrical signal. These detectors may be photodiodes, photoresistors, or photomultipliers.
Photometry uses Beer–Lambert’s law to calculate coefficients obtained from the
transmittance measurement. A correlation between absorbance and analyte concentration is
then established by a test-specific calibration function to achieve highly accurate
measurements.The testing procedure involves collecting a blood sample from the patient,
usually through venipuncture. The sample is then sent to a laboratory for analysis using
automated analyzers or manual techniques. Results are typically reported within a few days,
depending on the laboratory's turnaround time.

Interpretation of liver function test results requires consideration of the patient's clinical
history, symptoms, and other diagnostic tests. Abnormal results may indicate liver disease,
but further evaluation is often necessary to determine the underlying cause and appropriate
management

Interfering Factors:
Several factors can interfere with the accuracy and interpretation of liver function test (LFT)
results. These factors can include:

Medications and Drugs:

Certain medications and drugs can affect liver enzyme levels and other LFT parameters. For
example, hepatotoxic medications, such as acetaminophen (paracetamol), statins, certain
antibiotics, and antiepileptic drugs, can elevate liver enzymes.

Herbal supplements and recreational drugs may also interfere with LFT results.

Alcohol Consumption:
Excessive alcohol consumption can cause liver damage and elevate liver enzyme levels,
particularly gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and
aspartate aminotransferase (AST).

Pregnancy:
Pregnancy can lead to physiological changes in liver function, including alterations in liver
enzyme levels and bilirubin metabolism.

Hemolysis:
Hemolysis, the breakdown of red blood cells, can release enzymes into the bloodstream,
leading to falsely elevated levels of AST, ALT, and other enzymes.

Hemolysis, icterus, and lipemia are the most common specimen integrity issues that can
interfere with laboratory tests and may lead to erroneous results and interpretations and,
ultimately, to inappropriate medical decisions. Lipemia causes light scattering, differential
partitioning of analyte between the polar and aqueous phases of the sample, and interaction of
the lipoprotein particles with assay reagents may all cause interference in results. Lipaemia
causes light scattering across the visual spectrum (300 to 700 nm). Colorimetric assays taking
absorbance readings at the shorter wavelengths of the visual spectrum are, therefore, most
susceptible to interference. As a result, assays that utilize changes in NAD(P)H
concentration, measured around 340 nm, are susceptible to lipaemia interference. ALT levels
can increase due to certain drugs, which should be avoided before testing.

Quality control and Lab safety:

Quality control in liver function tests is all about making sure that the test results are accurate
and reliable. This is done by regularly calibrating the equipment used for the tests and using
quality control samples. These samples have known values that are used to check if the test is
working properly. By comparing the results of the quality control samples to the expected
values, any issues or errors can be identified and fixed.
When it comes to lab safety, it's super important to take precautions to protect yourself and
others. Here are a few key things to keep in mind:

1. Personal protective equipment (PPE):

Make sure to wear the right gear, like gloves, lab coats, and safety goggles, to keep yourself
safe from any potential hazards.

2.Handling chemicals:

Be careful when working with chemicals used in liver function tests. Follow proper handling
and storage procedures, and always label your chemicals correctly.

3. Equipment safety:
Regularly maintain and calibrate your lab equipment, like spectrophotometers and analysers
to make sure they're working correctly and safely.

4. Waste disposal:
Dispose of any hazardous materials, such as blood samples or contaminated items, according
to the proper guidelines to prevent any infections from spreading.

5. Emergency Preparedness:
Know what to do in case of emergencies, like spills or fires. Make sure you're familiar with
the emergency protocols, know where the exits are, and where to find safety equipment.

By following these quality control and lab safety practices, you can ensure accurate test
results and keep everyone safe in the lab.

Enhancing health care team outcomes:

Liver function tests are one of the most commonly ordered laboratory tests. Mild isolated
elevations in LFTs can be seen as normal fluctuations and shall not trigger expensive and
extensive workups. However, clinicians shall be aware of various conditions that can lead to
an elevation in LFTs. Thorough history taking and physical examination can provide clues to
the differential diagnosis. And improving teamwork and collaboration in liver function tests
is important for better patient care. Here are some simple ways to make the healthcare team
work better together:

1. Effective communication:
It's important for everyone on the healthcare team to communicate clearly and share
information about the patient's condition and test results. This helps everyone understand
what's going on and make the best decisions.

2. Work together:
Different healthcare professionals, like doctors, nurses, and lab technicians, should work
together and share their knowledge. This helps make sure everyone has the right information
and can provide the best care.

3. Follow guidelines:
It's helpful to have rules and guidelines that everyone follows when doing liver function tests.
These rules make sure that everyone is doing the tests in the same way and getting accurate
results.

4. Keep learning:
It's important for healthcare professionals to keep learning and stay up-to-date with the latest
information about liver function tests. This helps them provide the best care and make sure
they're doing the tests correctly.

5. Improve Quality:
Healthcare teams should always be looking for ways to make their work better. This could
mean checking their results regularly, getting feedback, and finding ways to do things more
efficiently and accurately.

By working together, following guidelines, learning, and improving quality, healthcare teams
can make sure liver function tests are done well and patients get the best care possible.

Results of Liver Function test:

The results of liver function tests should correlate with the initial findings in a complete
patient history and physical examination. A thorough review should include important
questions regarding the patient's age, and past medical history which may include:

 Diabetes
 Obesity
 Hyperlipidemia
 Inflammatory bowel disease
 Celiac sprue,
 Thyroid disorders
 Autoimmune hepatitis
 Acquired muscle disorders
 Alcohol use disorder
 Medication use
 Toxin exposure
 Family history of genetic liver conditions (Wilson disease, alpha-1-antitrypsin
deficiency, hereditary hemochromatosis).

Signs and Symptoms of Chronic Liver Diseases:

A review of systems should also include signs and symptoms of chronic liver disease such as
jaundice, ascites, peripheral edema, hepatosplenomegaly, gynecomastia, testicular
hypotrophy, muscle wasting, encephalopathy, pruritus, and gastrointestinal bleeding.

Other tests that help determine the cause of elevated transaminase levels found on a hepatitis
panel include fasting lipid levels, hemoglobin A1C level, fasting glucose, complete blood
count with platelets, a complete metabolic panel, iron studies, hepatitis C antibody, and
hepatitis B surface antigen testing.

Reporting and Clinical Findings:

Reference ranges for LFTs tend to vary depending on the laboratory. Further, normal
reference ranges vary between males and females and may be higher for those with a higher
body mass index. A patient's blood test values should be interpreted based on the reference
value of the laboratory in which the test is done. It is recommended that each laboratory
establish its own reference interval based on its methodology.

 Alanine transaminase (ALT): 0 to 45 IU/L.

 Aspartate transaminase (AST): 0 to 35 IU/L.
 Alkaline phosphatase (ALP): 30 to 120 IU/L.
 Gamma-glutamyltransferase (GGT): 0 to 30 IU/L.
 Bilirubin: 2 to 17 micromoles/L.
 Prothrombin time (PT): 10.9 to 12.5 seconds.
 Albumin: 40 to 60 g/L.
 Total proteins: 3 to 8.0 g/dL.
 LD: 122 to 222 U/L.
 5'-nucleotidase test: 2 to 17 units per liter

Clinical Significance of Liver Function Test:

The levels of LFTs can point to the differentials. Many disease processes have very distinct
abnormalities in the liver enzymes. Further investigation is warranted if repeated tests
confirm abnormality.

Alcohol:
In patients with alcohol use disorder, the AST to ALT ratio is generally at least 2:1, showing
a high level of AST activity in alcoholic liver disease. Elevated GGT, along with AST, also
suggests alcohol abuse. GGT should not be used alone since it is not very specific for alcohol.

Medications:
Several medications are known to cause liver damage. Many of these are commonly used in
daily practice, including but not limited to NSAIDs, antibiotics, statins, anti-seizure drugs,
and drugs for tuberculosis treatment.
  Acute hepatocellular injury can be seen secondary to several drugs, including but not
limited to acetaminophen, allopurinol, NSAIDs, alcohol, anti-tuberculosis
medications such as isoniazid, pyrazinamide, rifampin, statins, antifungals such as
ketoconazole, antibiotics such as tetracyclines, anti-seizure drugs such as valproic
acid and phenytoin, antidepressants such as fluoxetine, antipsychotics such as
risperidone and antivirals such as valacyclovir and ritonavir.
 Acute cholestasis can be seen secondary to drugs, including anabolic steroids,
NSAIDs, tricyclic antidepressants, alcohol, antibiotics such as azithromycin,
amoxicillin, nafcillin, rifampin, and trimethoprim-sulfamethoxazole. Long-term use
of these agents can also lead to chronic hepatocellular and/or cholestatic liver damage.
 Methotrexate, the commonly used medication for rheumatoid arthritis and other
inflammatory arthritis, can cause a mild transient elevation in LFTs and can also
cause permanent liver damage in liver fibrosis and cirrhosis, especially with higher
cumulative doses.
 Liver fibrosis can also be seen as secondary to chronic alcohol intake or methyldopa.
Ergot alkaloids can result in ischemic necrosis. Oral contraceptives can result in
hepatic venous outflow obstruction (Budd-Chiari syndrome). Herbal medications can
also cause an elevation in LFTs.

Viral Hepatitis:
Viral illnesses are a common cause of hepatitis and elevation in LFTs. Viral hepatitis B, C,
and D can cause chronic hepatitis, while hepatitis A and E cause acute viral hepatitis. Several
other viruses, including HIV, Epstein-Barr (EBV), and Cytomegalovirus (CMV), can also
cause hepatitis.

Autoimmune Hepatitis:
Autoimmune hepatitis is a chronic disease characterized by continuing hepatocellular
inflammation, necrosis, and a tendency to progress to cirrhosis. It is more common in young
women than men, with a 4:1 ratio. The patient usually presents with high LFTs without
apparent cause. These patients can have positive autoantibodies, including antinuclear
antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal antibodies, and
antibodies to the liver antigen.

Hepatic Steatosis and Nonalcoholic Steatohepatitis:

Fatty liver disease, aka nonalcoholic steatohepatitis, has recently gained more attention
because of its ability to cause chronic hepatic disease and hepatocellular carcinoma (HCC).
The typical patient with this disease is overweight, has type II diabetes, or has dyslipidemia
and no evidence of clinically significant alcohol use. The AST and ALT are usually both
elevated with a ratio of 1:1, with other liver function tests being normal.

Hemochromatosis:
Hemochromatosis is abnormal iron accumulation in parenchymal organs, leading to organ
toxicity. It is the most common autosomal recessive genetic disorder and the most common
cause of severe iron overload. Clinical manifestations include diabetes, liver disease, and
cutaneous hyperpigmentation. A raised serum ferritin level usually raises concerns for
possible hemochromatosis, but a transferrin saturation greater than 45% is more reliable. HFE
mutations (C282Y, H63D) are pivotal for diagnosing hereditary hemochromatosis. Secondary
hemochromatosis can also be seen due to increased iron intake.

Wilson Disease:
Wilson disease, a rare autosomal-recessive inherited disorder of copper metabolism, is
characterized by excess copper deposition in the liver, brain, and other tissues. It is fatal if not
recognized and treated early. A low serum ceruloplasmin level is seen in the majority (up to
85%) of the cases. Kayser-Fleischer rings can be a clinical clue but are not always present.
The 24-hour urinary copper excretion test is usually abnormal, with more than 100
micrograms of copper excretion in the urine indicating Wilson's disease. A liver biopsy
remains the confirmatory test.

Alpha-1 Antitrypsin Deficiency:

Alpha-1 antitrypsin deficiency (AATD) is a relatively common yet often undiagnosed genetic
condition. Those with AATD are also predisposed to obstructive pulmonary disease and liver
disease (e.g., cirrhosis and hepatocellular carcinoma in children and adults). AATD is one of
the most common inherited disorders among Caucasians. Its primary manifestation is early-
onset panacinar emphysema.

Celiac Disease:
Celiac disease is a common gluten sensitivity disorder associated with modest elevations of
liver transaminases; screening should be considered in patients with persistently elevated
liver enzymes and consists of tissue transglutaminase IgA and serum IgA level or tissue
transglutaminase IgA and anti-deamidated gliadin peptide IgG.

Thyroid Disorders:
Both hypothyroidism and hyperthyroidism have been associated with abnormal liver
enzymes, including both hepatocellular and cholestatic patterns of injury, particularly in more
severe cases of myxedema and/or thyrotoxicosis. Screening should be considered in patients
with a compatible medical history and consist initially of thyroid stimulating hormone and
selective testing of free T4 and free/total T3.

How Actual Tests Report Looks Like?

Price of Liver Function Test in Pakistan:
The prices for liver function tests in Pakistan vary depending on the laboratory and location.
However, here are some prices for liver function tests in Pakistan.
 Dawaai: Rs. 1400 to Rs. 1650
 Healthwire: Rs. 1000 to Rs. 2000
 Chughtai Lab: Rs. 1050 to Rs. 3000 (with discounts available)

Please note that these are general estimates and may vary based on your location and specific
laboratory or healthcare provider. It's best to consult with your healthcare provider or contact
the laboratory directly for accurate pricing information.