Liver Function Tests
by Dr. Sandra Cabot
Summary
This page will help you understand the reasons for liver function tests,
and explain the results.
It is not intended to encourage "self diagnosis".
A reliable diagnosis of a liver condition can only be made by a qualified
medical practitioner after many factors have been investigated and ruled
out. This will involve taking a full medical history and (more than likely)
more tests will need to be performed.
It is always recommended to see your physician if you suspect you have
a liver problem.
What causes the enzymes to be raised in a Liver Function Test?
The reason why all or some of these enzymes become elevated in cases
of liver disease is that they are normally contained inside the liver
cells (hepatocytes). They only leak into the blood stream when the liver
cells are damaged. Thus measuring liver enzymes is only able to detect
liver damage and does not measure liver function in a sensitive way. "The
Healthy Liver and Bowel Book" Dr. Sandra Cabot p 98
Other tests can be done to check the ability of the liver to manufacture
its vital proteins. These are tests for the proteins albumin, prothrombin,
and various globulins and they show characteristic abnormalities in those
whose liver function is abnormal. This may sound rather technical, however
your doctor can easily do all these tests from two or three small vials
of collected blood. In the early stages of liver disease there may be
no dramatic symptoms and thus you and your doctor may be totally unaware
that there is an underlying problem. Often the early stages of liver disease
are found coincidentally on a routine blood test that includes tests for
liver function.
Tests For Liver Function
What is a Liver Function Test?
Blood samples are analyzed for levels of specific enzymes in the blood
stream - there are generally 5 - 6 specific things that are checked. Collectively
these tests are called a "Liver Function Test" or LFT. These enzymes are
what are referred to as "markers" of disease and dysfunction.
This is not to be confused with a 'Functional Detoxification Profile"
which tests the function of the detoxification pathways
How reliable is this test?
The name "Liver Function Test" is actually quite misleading as this
test does not actually measure the "function" of the liver.
It is more a marker of the status of the integrity of the liver cell membranes.
Most of the standard or routine blood tests that your doctor will order
to check "liver function" are in reality only able to detect liver disease.
These tests are not sensitive enough to accurately reflect liver function.
It is possible to still have liver disease even though blood tests are
normal. Therefore the LFT alone is not capable of making a proper diagnosis
of many liver conditions. No test is completely accurate as it is only
an indication of what is happening at the time the test was taken. It
is therefore common practice to perform the test again on another occasion,
especially if any results are abnormal.
This is why it is important for you to consult a specialist in liver
diseases (hepatologist), if you suspect that your liver is unhealthy and
yet conventional blood tests remain normal.
Different diseases of the liver will cause differing types of damage
and affect liver function tests accordingly. It can be possible to give
an idea of which disease may be suspected from a liver function test,
but these tests are not the absolute way of diagnosing liver disease.
They are helpful, but not the whole story. They are also useful for monitoring
someone with liver disease, but are not always accurate.
As the LFT is really only showing the level of enzymes present in the
blood stream it is only showing that some damaging is occurring but does
not give an indication of the extent. This is where other tests are required
to give a more accurate picture of the extent of the damage after the
fact that damage is occurring has been established.
What is checked in a Liver Function Test?
A routine blood test for liver function will be processed by an automated
multichannel analyzer, and will check the blood levels of the following
:-
A Typical Liver Function Test
- AP (Alk Phos) U/L (30 to 120)
- GGT (Gamma GT) U/L (5 to 35)
- LD Lactate Dehydrogenase U/L (100-225)
- AST (Aspartate aminotransferase) U/L (5 to 45)
- ALT (Alanine aminotransferase) U/L (5 to 45)
- Albumin g/L (38-55)
- Clotting Studies (Prothrombin Time) Seconds (11 to 13.5)
- Total Bilirubin - Normal range is 3 - 18 umol/L (0.174 - 1.04mg/dL).
After the result is the laboratories reference range and the units in
which the result is expressed eg: U.L
Each laboratory will provide a "reference range" or "normal values"
This is the average reading that is deemed a "normal" reading
for the majority of the population. This will assist the Doctor in determining
if the patients results are abnormal.
The normal values for liver function tests will vary between men and
women, at different times of the day and will change as you get older.
Different laboratories may have slightly differing reference ranges.
Liver Enzymes
ALT - (alanine aminotransferase)
Previously called SGPT is more specific for liver damage. The ALT is an
enzyme that is produced in the liver cells (hepatocytes) therefore it
is more specific for liver disease than some of the other enzymes . It
is generally increased in situations where there is damage to the liver
cell membranes. All types of liver inflammation can cause raised ALT.
Liver inflammation can be caused by fatty infiltration (see fatty liver)
some drugs/medications, alcohol, liver and bile duct disease.
AST - (aspartate aminotransferase)
Previously called SGOT. This is a mitochondrial enzyme that is also present
in heart, muscle, kidney and brain therefore it is less specific for liver
disease. In many cases of liver inflammation, the ALT and AST activities
are elevated roughly in a 1:1 ratio.
AP - (alkaline phosphatase)
Is elevated in many types of liver disease but also in non-liver related
diseases. Alkaline phosphatase is an enzyme, or more precisely a family
of related enzymes, that is produced in the bile ducts and sinusoidal
membranes of the liver but is also present in many other tissues. An elevation
in the level of serum alkaline phosphatase is raised in bile duct blockage
from any cause. Therefore raised AP in isolation will generally lead a
physician to further investigate this area. Conditions such as Primary
Biliary Cirrhosis and Sclerosing Cholangitis will generally show a raised
AP. Raised levels may also occur in cirrhosis and liver cancer. Alkaline
phosphatase is also produced in bone and blood activity can also be increased
in some bone disorders.
GT - (gamma glutamyl transpeptidase)
Is often elevated in those who use alcohol or other liver toxic substances
to excess. An enzyme produced in many tissues as well as the liver. Like
alkaline phosphatase, it may be elevated in the serum of patients with
bile duct diseases. Elevations in serum GGT, especially along with elevations
in alkaline phosphatase, suggest bile duct disease. Measurement of GGT
is an extremely sensitive test, however, and it may be elevated in virtually
any liver disease and even sometimes in normal individuals. GGT is also
induced by many drugs, including alcohol, therefore often when the AP
is normal a raised GGT can often (but not always) indicate alcohol use.
Raised GGT can often be seen in cases of fatty liver and also where the
patient consumes large amounts of Aspartame (artificial Sweetener) in
diet drinks for example.
Bilirubin
Is the major breakdown product that results from the destruction of old
red blood cells (as well as some other sources). It is removed from the
blood by the liver, chemically modified by a process call conjugation,
secreted into the bile, passed into the intestine and to some extent reabsorbed
from the intestine. It is basically the pigment that gives feces its brown
color Bilirubin concentrations are elevated in the blood either by increased
production, decreased uptake by the liver, decreased conjugation, decreased
secretion from the liver or blockage of the bile ducts. In cases of increased
production, decreased liver uptake or decreased conjugation, the unconjugated
or so-called indirect bilirubin will be primarily elevated. In cases of
decreased secretion from the liver or bile duct obstruction, the conjugated
or so-called direct bilirubin will be primarily elevated.
Many different liver diseases, as well as conditions other than liver
diseases (e. g. increased production by enhanced red blood cell destruction),
can cause the serum bilirubin concentration to be elevated. Most adult
acquired liver diseases cause impairment in bilirubin secretion from liver
cells that cause the direct bilirubin to be elevated in the blood. In
chronic, acquired liver diseases, the serum bilirubin concentration is
usually normal until a significant amount of liver damage has occurred
and cirrhosis is present. In acute liver disease, the bilirubin is usually
increased relative to the severity of the acute process. In bile duct
obstruction, or diseases of the bile ducts such as primary biliary cirrhosis
or sclerosing cholangitis, the alkaline phosphatase and GGT activities
are often elevated along with the direct bilirubin concentration. (See
Gilberts Syndrome)
Albumin
Albumin is the major protein that circulates in the bloodstream. As
it is made by the liver and secreted into the blood it is a sensitive
marker and a valuable guide to the severity of liver disease. Low serum
albumin concentrations indicate the liver is not synthesizing the protein
and is therefore not functioning properly. The serum albumin concentration
is usually normal in chronic liver diseases until cirrhosis and significant
liver damage is present. There are many other proteins synthesized by
the liver however the Albumin is easily, reliably and inexpensively measured.
Platelet count
Platelets are cells that form the primary mechanism in blood clots. They're
also the smallest of blood cells. They derived from the bone marrow from
the larger cells known as megakaryocytes. Individuals with liver disease
develop a large spleen. As this process occurs platelets are trapped with
in the sinusoids (small pathways within the spleen) of the spleen. While
the trapping of platelets is a normal function for the spleen, in liver
disease it becomes exaggerated because of the enlarged spleen (splenomegaly).
Subsequently, the platelet count may become diminished.
Prothrombin time (Clotting Studies)
The prothrombin time is tested to evaluate disorders of blood clotting,
usually bleeding. It is a broad screening test for many types of bleeding
disorders. When the liver is damaged it may fail to produce blood clotting
factors.
How do the liver cell membranes get damaged in the first place?
Inflammation is a common cause of damage to the delicate liver cell
membranes. Liver inflammation is medically termed Hepatitis (hepato =
liver, itis = inflammation). This has many different causes including
long term alcohol excess, some medications such as long term antibiotics,
cholesterol lowering medications and pain killers, oral synthetic Hormone
Replacement, viral infections of the liver such as Hepatitis A, B &
C, auto-immune hepatitis, hemachromatosis, primary biliary cirrhosis,
exposure to toxic chemicals such as insecticides & pesticides &
organic solvents & incorrect diet.
Fatty liver can cause raised Liver Function Test results
One of the most common causes of liver inflammation is fatty liver (see
Fatty Liver) Fatty liver is also known as NASH, which stands for Non-
Alcoholic Steatorrhoeic Hepatosis. It is very common in overweight persons,
over the age of 30 who have had a long term poor diet high in processed
foods, sugar, saturated fat and dairy products.
Generally an ultrasound of the abdominal area should also be performed.
Many cases of fatty liver can be picked up this way. The ultrasound will
detect areas "of increased echogenicity" meaning that the liver
tissue is beginning to become infused with fat.
What can be done to lower the readings?
In my medical practice where I do a lot of routine blood tests for hormone
levels and liver function in overweight patients, I often find slight
elevations in liver enzymes which signifies mild impairment of liver function
and slight liver damage. This can easily be reversed with the Liver Cleansing
Diet principles and specific dietary supplements I have found that it
is very difficult for many of my overweight patients to lose weight even
though they may be eating only normal amounts, unless I first improve
their liver function. Once they are five to six weeks into the "Liver
Cleansing Diet" their liver-function tests are usually back to normal
and the process of weight loss takes on increased momentum. Yes, the liver
is the strategic organ for those who have found it very difficult to lose
weight or simply just to maintain a healthy weight as they get older.
"The Liver Cleansing Diet" Dr. Sandra Cabot p 20.
Tests for Liver Disease
If you suspect that your liver is not working properly or may be diseased
ask your doctor to check your liver. The liver can be seen with various
imaging techniques, such as ultrasound scanning or CAT scanning, which
are done by a radiologist. An ultrasound scan of the upper abdomen will
show the size and shape of the liver, gallbladder, spleen, and pancreas.
CAT scanning is used to check for cancer or tumors of the liver.
Blood tests can check levels of serum bilirubin and bile acids, which
may be elevated in certain types of liver and gallbladder disease. If
the bilirubin is too high you may also notice that your bowel actions
are very pale and that your urine is a darker color because bilirubin
is diverted from the bowels to the urine.
When diagnosing liver disease, often, but not always the most used test
in each disease is generally:
Disease Test or Procedure
Fatty liver (Nonalcoholic Steatohepatitis or NASH)
Hepatitis A
- Antibody Test (Blood Sample)
Hepatitis B
- Antibody & Antigen Tests Hepatitis B DNA (Blood Sample)
- Liver Biopsy if chronic to assess level of liver damage
Hepatitis C
- Antibody Test/ Hepatitis C RNA (Blood Sample)
- Liver Biopsy if chronic to assess level of liver damage
Primary Biliary Cirrhosis
- Biopsy/ Bile duct imaging Primary Sclerosing Cholangitis
- Biopsy/ Bile duct imaging
Autoimmune Hepatitis
Wilson"s Disease
- Genetic Analysis/ Copper studies (Blood and Urine Samples)
Alcohol Related Liver Disease
- Liver Biopsy/ Liver Function Tests
What is a Biopsy?
This procedure involves using a special needle to remove tissue from
the liver to be examined in the laboratory. This will be used to assess
the extent of scarring, fatty infiltration or liver damage. For the biopsy,
you will lie on a hospital bed on your back or turned slightly to the
left side, with your right hand above your head. After marking the outline
of your liver and injecting a local anesthetic to numb the area, the physician
will make a small incision in your right side near your rib cage, then
insert the biopsy needle and retrieve a sample of liver tissue. In some
cases, the physician may use an ultrasound image of the liver to help
guide the needle to a specific spot.
How accurate is this test?
It is still regarded as the most accurate way of assessing the status
of the extent of damage to the liver. You will need to hold very still
so that the physician does not nick the lung or gallbladder, which are
close to the liver. The physician will ask you to hold your breath for
5 to 10 seconds while he or she puts the needle in your liver. You may
feel a dull pain. The entire procedure takes about 20 minutes.
Liver biopsy is considered minor surgery and is done at the hospital.
However it should be noted that this procedure is not without risk - it
is important that it is carried out by a very experienced Doctor. The
risks include puncture of the lung or gallbladder, infection, bleeding,
and pain. The bleeding in particular is a dangerous complication. It carries
about a 1/10000 death rate - some Doctors say its even higher.
Who should NOT have this procedure done?
- People with blood clotting disorders
- People who are on blood thinning medication such as Warfarin, Coumadins,
Ibuprofen, aspirin
- People with hemangiomas (benign liver cyst consisting of twisted congested
blood vessels)
What is an ultrasound or sonograph?
This is a non invasive method of assessing liver health. It is an imaging
procedure of the internal organs of the abdomen, including the liver,
gallbladder, spleen, pancreas and kidneys. The ultrasound machine sends
out high-frequency sound waves, which reflect off body structures to create
a picture. There is no ionizing radiation exposure with this test. There
are many reasons for performing an abdominal ultrasound including looking
for a cause of pain, for stones in the gallbladder or kidney, or for a
cause for enlargement of an abdominal organ. The reason for the examination
will depend on your symptoms.
Functional Tests of the Liver
Recently tests that assess the liver"s function, especially its
detoxification abilities, have become available. These tests are called
"Functional Liver Challenge Tests" or a "Functional Liver
Detoxification Profile". During these tests the liver is challenged
with caffeine, aspirin and paracetamol in safe oral doses. Samples of
urine and saliva are then collected at timed intervals and sent to the
laboratory where their levels of the excreted forms of these drugs are
measured. These tests are noninvasive and assess the ability of the liver
to detoxify and eliminate drugs and other chemicals. These tests are unique
in that they assess the functional capacity of the liver in both phase
one and phase two detoxification pathways. They can be conducted in the
patient"s home and are simple to perform. Your health care practitioner
can arrange them for you.
Functional Liver Detoxification Profile (FLDP)
- This is a noninvasive challenge test to assess the efficiency of the
liver to detoxify and eliminate toxic chemicals. Assessing multiple
pathways with challenge substances provides clinical information about
individuals with imbalanced detoxification.
- Assess cumulative liver function impairment.
- Evaluate risk of free radical damage due to impaired liver function.
- Provide information on the liver's ability to process toxic loads.
- Monitor effectiveness of detoxification programs.
The Functional Liver Detoxification Profile provides valuable information
for patients with:
- Altered Intestinal Permeability
- Autoimmune Disease
- Chronic Fatigue Syndrome
- Encephalopathy
- Food Allergies
- Headaches
- Hepatitis
- Infectious Bowel Disease
- Intestinal Toxaemia
- Chemical Sensitivities
- Premenstrual Tension
- Exposure to Xenobiotics
Test Principle
Low doses of Caffeine, Aspirin and Paracetamol are taken orally. Saliva
and urine samples are collected at timed intervals and sent to the laboratory
for analysis.
Test Procedure
CAFFEINE / ASPIRIN / PARACETAMOL An average dose of 200mg of caffeine
(equivalent to two cups of strong coffee) is taken in the morning and
its clearance rate (Phase I) is determined by analyzing two saliva samples
taken at prescribed time intervals after ingestion. Aspirin (650mg) and
paracetamol (acetaminophen) (750mg) are taken before going to bed and
urine is collected over the following 10 hours. The total volume of urine
is noted and a sub sample taken off for analysis.
Please NOTE:
- Standard liver enzyme tests (LFTs) only assess existing pathological
damage to hepatocytes.
- Administration of therapeutic substances MUST be carried out under
the supervision of a medical practitioner.
- It is important that you read instructions accompanying the special
test kit received from the analytical laboratory and the advice/warning
information thoroughly before proceeding with the test.
- Ensure that you have NOT taken Aspirin or Paracetamol within 48 hours
of commencing the test.
- The test is best performed over a 24 hour period.
- Advise your Practitioner if you suffer from asthma/ hay fever.
- Application of this test to children between the ages of 2-12 MUST
be conducted under the supervision of a medical practitioner. Separate
test kits are available for adults and children.
General Information
The test samples can be easily collected in the patient's home.
Specially prepared specimen collection kits are available from the recommended
laboratories listed.
Full test details and collection instructions are included in the test
kits.
Sample specimen collection regime
DAYTIME
Procedure Write your name and date on the two saliva sample tube labels
(#1 and 2).
8.00am Take caffeine tablets before breakfast (see advice/warning information
for dose). Assume normal diet i.e. breakfast.
NOTE: Do not consume any foods containing caffeine
(coffee, chocolate, colas) during the test period and for approximately
6 hours thereafter (see advice/waning information).
10.00am Collect 1st sample by expressing saliva into the tube (labeled
1st Saliva Sample) up to the bottom of the label (1ml). Assume normal
diet i.e. lunch and snacks.
4.00pm Collect 2nd sample by expressing saliva into the tube (labeled
2nd Saliva Sample) up to the bottom of the label (1ml). Store samples
in plastic bag provided, reseal and place in refrigerator away from food.
OVERNIGHT
Procedure
10.00pm Write your name and date on the Pretest and 10 Hour Urine Sample
tubes. Cease eating and drinking (except water).
Pass urine sample into small plastic container then empty bladder.
Using the pipette fill the yellow cap Pretest tube and discard remaining
urine.
Store the Pretest tube with the saliva samples in the refrigerator.
10.10pm Take aspirin and paracetamol tablets and note time (see advice/warning
information).
Collect all overnight urine in graduated 1 liter plastic bottle.
8.10am Collect/add first morning urine into graduated 1 liter plastic
bottle, giving a total 10 hours collection.
Read total urine volume and write on the request slip & the 10 Hour
Urine Sample tube.
Using pipette, fill 10 Hour Urine Sample tube and discard remaining urine.
NOTE: The times listed for the test procedure are suggestions only.
You may want to plan a schedule to suit your convenience in which case
you must remember to observe the time intervals.
ADVICE: The individual doses of Caffeine, Aspirin and Paracetamol used
in this test are lower than the general ADULT therapeutic course doses
prescribes by Medical Practitioners (ie the test calls for one dose whereas
a course dose requires multiple doses at regular time intervals). The
use of these drugs, however, may be contraindicated in young children,
pregnancy, concurrent use of other drugs and in certain clinical conditions.
Please read the following warnings and refer to your Medical Practitioner
if in doubt.
WARNINGS:
CAFFEINE
Test Dose: 100-300 mg depending on body weight.
If your body weight is:
less than 80lbs/36kg then take 1 tablet
from 80lbs/36kg to 130lbs/59kg then take 2 tablets
over 130lbs/59kg then take 3 tablets
NOTE: Each tablet contains 100 mg caffeine which is the equivalent of
one cup of coffee.
Contraindications: None reported.
Adverse Reactions: Although uncommon, some people may experience heightened
nervousness, irritability, sleeplessness and occasionally rapid heart
beat.
ASPIRIN
Test Dose: 750 mg
Contraindications: Bleeding disorders, severe hepatic disease, kidney
disease, uraemia, erosive gastritis, peptic ulcer, asthma, hypersensitivity
to aspirin and other salicylates; patients taking anticoagulant therapy;
concurrent use of alcohol.
Adverse Reactions: Gastrointestinal disturbances such as nausea, dyspepsia
(same for single dose)
PARACETAMOL
Test Dose: 750 mg
Contraindications: None reported.
Adverse Reactions: While reports of adverse reactions are rare, mild effects
such as dyspepsia, nausea, allergenic and hematological reactions have
been reported. However a causal relationship to the administration of
paracetamol has neither been confirmed or refuted.
DIETARY RESTRICTIONS
The following dietary restrictions must be observed for the Functional
Liver Detoxification Profile. DO NOT consume the following foodstuffs
before or during the test: Coffee, tea, cocoa, chocolate, cola soft drinks;
Medication containing caffeine or salicylates; Fruit, stoned fruits, dried
fruits (eg. sultanas, currants, raisins etc); Licorice, aniseed, peppermint
(eg. sweets, lollies, gums etc); Spices (eg. curry, dill, oregano, paprika
etc). These foods contain many of the substates for which the liver is
being tested. To keep the test controlled and make the results meaningful
- outside sources of the chemicals must not be consumed.
Functional Liver Detoxification Profile - FLDP, Interpretive Guide
Phase I - P450 Detoxification
Low caffeine clearance (Phase I) Indicates slow P-450 enzyme activity
and metabolic detoxification difficulty due to enzyme inhibitors e.g.
drugs, toxic metals, enterotoxins, liver damage, and/or insufficient nutrient
cofactors. May also reflect use of medications such as amphetamines, cimetidine,
and oral contraceptives.
High caffeine clearance (Phase I) Reflects excessive P-450 enzyme induction,
possibly due to exposure to cigarette smoking, alcohol, drugs (prescribed
and illicit), and absorption of enterotoxins (i.e. leaky gut). Also implies
greater production of free radicals therefore can indicate an increased
risk of free radical damage.
Low Sulphate/Creatinine Ratio Reflects: Low amount of glutathione and
sulphate available for detoxification. Excess exposure to xenobiotics.
Increased free radical activity. Molybdenum deficiency (required for conversion
of sulfites to sulfates). High Sulphate/Creatinine Ratio A high sulphate/creatinine
ratio suggests adequate levels of glutathione and efficient sulfation
conjugation.
Phase II - Conjugation Pathways
Low Glutathionation: indicates low levels of glutathione available for
removal of toxic intermediate metabolites and increased risk of free radical
activity. Low sulfation: inadequate sulphate reserves for conjugation
of bio-transformed molecules especially steroid hormones, drugs, xenobiotics
and phenolic compounds. Low Glucuronidation: may also indicate low sulfation
or glycination. Glucuronidation is an important pathway when sulfation
and/or glycination are compromised. Low Glycination: limited glycine available
for salicylate conjugation. Increased risk of free radical activity.
A High Phase II Result: Indicates increased burden for specific conjugation
pathways. Prolonged stress on a particular pathway will cause an increase
in free radical damage which, in turn, will reduce liver function in the
long term. Low acetaminophen mercapturate, salicyluric acid, acetaminophen
sulfate or acetaminophen glucuronide (Phase II): Indicate inadequate Phase
II conjugation reactions. Low levels may reflect depletion of the particular
amino acids or nutrient cofactors used in the reactions, or diminished
enzymatic capacity for conjugation. Elevated Phase I/Phase II ratios:
May reflect elevated (induced) Phase I processes or diminished Phase II
conjugation reactions. The ratio of Phase I to Phase II detoxification
processes is important in determining the toxicity of certain drugs, and
these ratios may be significant indicators of the balance of biological
processes.
Where can these test kits be obtained from?
Your medical practitioner may request the Functional Detoxification
Profile Test kit from the following laboratories:
In the USA:
The Great Smokies Laboratories
18A Regent Park Boulevarde, Ashville
North Carolina, USA, 28806
Phone: (828) 285 2223
In Australia:
Analytical Reference Laboratories Pty Ltd
Postal - PO Box 279, North Melbourne 3051, Victoria, Australia
Laboratory - Ground Floor, 568 St Kilda Road, Melbourne, 3004.
Telephone: (03) 9529 2922 Facsimile: (03) 9529 2822
Email: info@arlaus.com.au Website: www.arlaus.com.au Est 1974
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