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Liver Function Tests

Liver Function Test

Summary

Learn 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 Liver Enzymes to be elevated 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 the Liver 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: uL

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)

  • Ultrasound
  • Liver Biopsy

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

  • Liver Biopsy

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.

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.


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