Liver Function Test – Types, Purpose, Result of Abnormality

Liver Function Test – Types, Purpose, Result of Abnormality

Liver Function Test is a misnomer as many of the tests do not comment on the function of the liver but rather pinpoint the source of the damage. Elevations in ALT and AST in out of proportion to ALP and bilirubin denotes a hepatocellular disease. Whereas, an elevation in ALP and bilirubin in disproportion to ALT and AST would denote a cholestatic pattern. The actual function of the liver can be graded based on its ability to produce albumin as well as vitamin K dependent clotting factors.

Causes of Elevated Liver Enzyme or Abnormal Function

Elevated LFTs are found in approximately 8% of the general population. These elevations may be transient in patients without symptoms with up to 30% elevations resolving after 3 weeks. Thus, care should be taken when interpreting these results to avoid unnecessary testing.

Differential Diagnosis Based on Elevated LFTs

Hepatocellular pattern – Elevated aminotransferases out of proportion to alkaline phosphatase

  • ALT-predominant Acute or chronic viral hepatitis, steatohepatitis, acute Budd-Chiari syndrome, ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins, autoimmune, alpha1-antitrypsin deficiency, Wilson disease, Celiac disease
  • AST-predominant – Alcohol-related, steatohepatitis, cirrhosis, non-hepatic (hemolysis, myopathy, thyroid disease, exercise)

Cholestatic pattern – elevated alkaline phosphatase + GGT + bilirubin out of proportion to AST  and ALT

  • Hepatobiliary causes  Bile duct obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, medication-induced, infiltrating diseases of the liver (sarcoidosis, amyloidosis, lymphoma, among others), cystic fibrosis, hepatic metastasis, cholestasis
  • Non-Hepatic causes of elevated alkaline phosphatase  Bone disease, pregnancy, chronic renal failure, lymphoma or other malignancies, congestive heart failure, childhood growth, infection or inflammation

If a person’s blood test results show elevated liver enzymes, a doctor will investigate possible underlying causes. They may do further tests in addition to asking about a person’s lifestyle and dietary habits. The most common cause of elevated liver enzymes is fatty liver disease. Research suggests that 25–51% of people with elevated liver enzymes have this condition.

Other health conditions that typically cause elevated liver enzymes include

  • Metabolic syndrome
  • Hepatitis
  • Alcohol or drug use disorder
  • Cirrhosis, which is liver tissue scarring
  • Autoimmune hepatitis
  • Celiac disease
  • Infection with the Epstein-Barr virus, a type of herpes
  • Liver cancer
  • Hemochromatosis, when the body absorbs too much iron
  • mononucleosis
  • Sepsis, or blood poisoning
  • Wilson’s disease
  • Polymyositis, which involves inflammation of the muscles

Results, Reporting, Critical Findings of Liver Function Test

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 higher body mass index.

  • Alanine transaminase: 0 to 45 IU/L
  • Aspartate transaminase: 0 to 35 IU/L
  • Alkaline phosphatase: 30 to 120 IU/L
  • Gamma-glutamyltransferase: 0 to 30 IU/L
  • Bilirubin: 2 to 17 micromoles/L
  • Prothrombin time: 10.9 to 12.5 seconds
  • Albumin: 40 to 60 g/L

Results

Normal blood test results for typical liver function tests include:

  • ALT. 7 to 55 units per liter (U/L)
  • AST. 8 to 48 U/L
  • ALP. 40 to 129 U/L
  • Albumin. 3.5 to 5.0 grams per deciliter (g/dL)
  • Total protein. 6.3 to 7.9 g/dL
  • Bilirubin. 0.1 to 1.2 milligrams per deciliter (mg/dL)
  • GGT. 8 to 61 U/L
  • LD. 122 to 222 U/L
  • PT. 9.4 to 12.5 seconds

Purpose

Liver function tests can be used to:

  • Screen for liver infections, such as hepatitis
  • Monitor the progression of a disease, such as viral or alcoholic hepatitis, and determine how well a treatment is working
  • Measure the severity of a disease, particularly scarring of the liver (cirrhosis)
  • Monitor possible side effects of medications

Liver function tests check the levels of certain enzymes and proteins in your blood. Levels that are higher or lower than normal can indicate liver problems. Some common liver function tests include:

  • Alanine transaminase (ALT) – ALT is an enzyme found in the liver that helps convert proteins into energy for the liver cells. When the liver is damaged, ALT is released into the bloodstream and levels increase.
  • Aspartate transaminase (AST) – AST is an enzyme that helps metabolize amino acids. Like ALT, AST is normally present in blood at low levels. An increase in AST levels may indicate liver damage, disease or muscle damage.
  • Alkaline phosphatase (ALP) – ALP is an enzyme found in the liver and bone and is important for breaking down proteins. Higher-than-normal levels of ALP may indicate liver damage or diseases, such as a blocked bile duct, or certain bone diseases.
  • Albumin and total protein – 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-normal levels of albumin and total protein may indicate liver damage or disease.
  • Bilirubin – Bilirubin is a substance produced during the normal breakdown of red blood cells. Bilirubin passes through the liver and is excreted in the stool. Elevated levels of bilirubin (jaundice) might indicate liver damage or disease or certain types of anemia.
  • Gamma-glutamyltransferase (GGT) – GGT is an enzyme in the blood. Higher-than-normal levels may indicate liver or bile duct damage.
  • L-lactate dehydrogenase (LD) – LD is an enzyme found in the liver. Elevated levels may indicate liver damage but can be elevated in many other disorders.
  • Prothrombin time (PT) – PT is the time it takes your blood to clot. Increased PT may indicate liver damage but can also be elevated if you’re taking certain blood-thinning drugs, such as warfarin.
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Why do I need a liver function test?

Liver tests can help determine if your liver is working correctly. The liver performs a number of vital bodily functions, such as:

  • Help diagnose liver diseases, such as hepatitis
  • Monitor treatment of liver disease. These tests can show how well the treatment is working.
  • Check how badly a liver has been damaged or scarred by disease, such as cirrhosis
  • Monitor side effects of certain medicines
  • removing contaminants from your blood
  • converting nutrients from the foods you eat
  • storing minerals and vitamins
  • regulating blood clotting
  • producing cholesterol, proteins, enzymes, and bile
  • making factors that fight infection
  • removing bacteria from your blood
  • processing substances that could harm your body
  • maintaining hormone balances
  • regulating blood sugar levels

Problems with the liver can make a person very sick and can even be life-threatening.

What are the symptoms of a liver disorder?

Symptoms of a liver disorder include:

  • Jaundice, a condition that causes your skin and eyes to turn yellow
  • Diarrhea
  • Abdominal pain
  • Dark-colored urine
  • Light-colored stool
  • Fatigue
  • Weakness
  • Fatigue or loss of energy
  • Weight loss
  • Jaundice (yellow skin and eyes)
  • Fluid collection in the abdomen, known as ascites
  • Discolored bodily discharge (dark urine or light stools)
  • Nausea – vomiting
  • Abdominal pain
  • Abnormal bruising or bleeding

You may also need these tests if you have certain risk factors. You may be at higher risk for liver disease if you

  • Have a family history of liver disease
  • Have alcohol use disorder, a condition in which you have difficulty controlling how much you drink
  • Think you have been exposed to a hepatitis virus
  • Take medicines that may cause liver damage.

What do unusually low levels on my liver function tests mean?

Note that in most cases (except albumin and calcium) it is a raised (rather than a lowered) level in the liver function test which may indicate a problem. In the following descriptions, where low levels can be significant for your health they are also described.

Bilirubin comes from the breakdown of red blood cells in the body. The liver processes (conjugates) bilirubin so that it can be excreted via the kidneys. A high bilirubin level can make you appear jaundiced (with a yellow tinge to the skin and to the whites of the eyes).

The most likely cause of raised bilirubin depends on whether the rise is in bilirubin that the liver has already processed (conjugated bilirubin), in the bilirubin that the liver has not yet processed (unconjugated bilirubin), or in both.

A rise in both types of bilirubin

Conjugated bilirubin tends to rise if the flow of bile in the tiny tubes within the liver is blocked, and unconjugated bilirubin tends to rise if the liver cells cannot do their work (or there is too much work for them to do). If the liver is both damaged (not working properly) and swollen or scarred (blocking the drainage system) then both types of bilirubin will tend to rise.

An isolated rise in unconjugated bilirubin

Unconjugated bilirubin may increase because the liver can’t process the bilirubin, or because the body is making an excess of bilirubin by breaking down too many blood cells, and the liver is normal but can’t keep up.

  • In adults, the most common causes are a breakdown of blood cells (hemolysis) and Gilbert’s syndrome.
  • Hemolysis as a condition of the blood. Further tests will be needed to identify the cause and you may need to see a hematologist. Causes can include reactions to medicines, lifelong (congenital) blood cell abnormalities such as hereditary spherocytosis and, in babies, breast milk jaundice, severe infection (sepsis), and hemolytic disease of the newborn.

An isolated rise in conjugated bilirubin

Increased conjugated bilirubin suggests that the liver is conjugating the bilirubin properly (the job of liver cells) but not excreting it properly via the bile ducts. Causes include:

  • Reactions to some medicines, including common ones such as blood pressure tablets, hormones (for example, estrogen), antibiotics (particularly erythromycin and flucloxacillin), tricyclic antidepressants and anabolic steroids.
  • Some autoimmune diseases that affect bile excretion.
  • Blockage of the bile ducts – for example, by a gallstone.
  • Dubin-Johnson syndrome and Rotor’s syndrome.
  • In babies, a rise in conjugated bilirubin can signify rare but serious problems with the development of the bile drainage system in the liver, such as biliary atresia.

Albumin is the main protein in your serum, and its level is a good guide to long-term liver health. Albumin levels that are abnormally low have the greatest significance for the liver.

Low levels of albumin

This can be due to:

  • Severe liver disease.
  • Poor nutrition.
  • Malabsorption of protein (for example, in Crohn’s disease or in coeliac disease).
  • Protein-losing enteropathies (for example, severe bowel inflammation or infection such as cholera).
  • Protein loss through kidney problems (for example, nephrotic syndrome).
  • Failure of protein manufacture through severe liver inflammation.
  • Albumin levels also fall if you lose protein through your skin (for example, in extensive skin inflammation and widespread burns).
  • Albumin levels decrease during pregnancy when your blood is more dilute.

High levels of albumin

This is usually due to having the tourniquet on for too long before your blood sample is taken. Sometimes it can be due to a very high-protein diet, as in bodybuilders, or to lack of fluid in the body (dehydration), when the blood is more concentrated.

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Total protein measures the total of albumin and globulins. It is usually normal in liver disease even if albumin levels are low, as globulin levels tend to increase as albumin levels fall.

  • High values of total protein are seen in chronic active hepatitis and alcoholic hepatitis.
  • High values of total protein are also seen in conditions outside the liver which increase globulins (such as myeloma) and conditions involving overactivity of the immune system (such as severe infection and chronic inflammatory disease).
  • Low levels of total protein can sometimes be seen in severe liver disease, in conditions of severe protein loss (such as widespread burns) and in severe malnutrition.

These substances are also called transferases. They are liver hormones (proteins that help do the work of the liver) which are normally found inside liver cells rather than in the blood.

  • ALT stands for alanine transaminase and is also called SGPT (serum glutamic-pyruvic transaminase).
  • AST stands for aspartate transaminase and is also called SGOT (serum glutamic oxaloacetic transaminase).
  • Creatine kinase is sometimes checked along with AST and ALT.

If blood levels of transaminases go up this suggests leakage from damaged liver cells due to inflammation or cell death. AST and ALT tend to be high in liver disease and very high in liver inflammation.

  • ALT is mainly found in the liver. AST is also found in muscle and red blood cells.
  • ALT rises more than AST in acute liver damage.
  • In chronic liver disease (for example, alcoholic cirrhosis) ALT is higher than AST; in cirrhosis, AST is higher than ALT.
  • Lower-than-normal levels of transaminases do not signify disease.
  • Creatine kinase comes mainly from muscle, so if it is raised alongside AST and ALT it suggests that the liver may not be the main source of the problem.

Causes of mild rises in transferases

These include:

  • Non-alcoholic fatty liver disease (the most common cause).
  • Chronic hepatitis C infection.
  • Coeliac disease.
  • Hemochromatosis (a genetic condition that tends to come on in your 40s or 50s).
  • Autoimmune hepatitis.

Causes of marked increases in transferases

Marked increases are usually caused by acute injury to the liver by viruses, shortage of oxygen (ischemia), or toxic substances. Causes include:

  • Acute alcoholic hepatitis.
  • Viral (hepatitis A, hepatitis B, hepatitis C, hepatitis D, or hepatitis E). Hepatitis A and B tend to have the greatest increases.
  • Autoimmune hepatitis.
  • Chronic hepatitis and liver cirrhosis.
  • Very high levels (>75 times upper reference limit) suggest ischaemic or toxic (poison or medicine related) injury to the liver.
  • Ischaemic liver damage is mostly seen in patients with other serious illnesses such as septicemia or collapse.

Gamma-glutamyltransferase (GGT) levels increase in most liver diseases. This test is very sensitive, although it also goes up in some heart, lung and kidney conditions.

  • The most common reason for GGT increasing as a single abnormality is drinking more alcohol than your liver can easily cope with. GGT levels can be 10 times normal. The rise is a sign your liver is under strain and is at risk of being damaged by alcohol.
  • GGT rises to 2-3 times the upper limit of normal in non-alcoholic fatty liver disease (NAFLD). This condition is increasingly common and can progress to scarring or inflammation of the liver. Transaminase levels also tend to rise in NAFLD.
  • Some prescribed and over-the-counter medicines can increase GGT levels.
  • GGT rises in some patients with chronic hepatitis C infection.
  • In chronic liver disease, a rise in GGT suggests bile duct damage and scarring.

Alkaline phosphatase (ALP) comes mainly from the cells lining bile ducts and from bones – particularly growing bones. It rises if there is slow or blocked flow in the bile ducts, if the bile ducts are damaged and in bone disorders. If the cause is in the liver, the GGT is also abnormal, whereas if it’s the bone, the GGT is usually normal. ALP is also raised during the third trimester of pregnancy.

Common causes of raised ALP with other abnormalities on your tests include

  • Gallstones.
  • Hepatitis of any cause.
  • Cirrhosis.
  • Bile duct blockage of any cause.

Isolated raised ALP can occur in

  • Sarcoidosis.
  • Bone fractures.
  • Paget’s disease of bone.
  • Osteomalacia.
  • Primary sclerosing cholangitis.
  • Primary biliary cholangitis.
  • Cancer in bones or in the liver.

99% of the body’s calcium is stored in the bones, with the remaining 1% stored in other tissues, including the blood plasma. The calcium test measures the total calcium in the blood plasma. About half of this is tightly attached to the protein, albumin, which forms the bulk of the protein in your plasma. The calcium level that really counts is the ‘free’, or unbound, calcium that floats unattached in the plasma.

If you have low albumin levels, the total calcium in your blood will be less; however, because the amount attached to the albumin is reduced (because there is less albumin), the actual free levels of calcium may be fine (or even raised). Corrected calcium corrects the figure to give the actual, free amount of calcium.

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Causes of low (corrected) calcium levels

Calcium levels are regulated by the kidney, thyroid, and parathyroid glands, using the hormones parathyroid hormone, calcitonin and vitamin D. Low levels are uncommon. Causes include:

  • Hypoparathyroidism (your parathyroid glands do not make enough of their hormone).
  • Just after parathyroid surgery.
  • Severe chronic kidney disease.
  • Severe liver disease.
  • Pancreatitis.
  • Severe vitamin D deficiency.
  • High phosphate ingestion (we can take in phosphate from enemas, from baby milk and from some flours – for example, chapati flour).
  • Magnesium deficiency (often due to dietary deficiency and to prescribed medicines, including some antibiotics, diuretics and painkillers).

Causes of raised (corrected) calcium levels

  • Primary hyperparathyroidism (overactive parathyroid glands) causes 8 out of 10 cases.
  • Cancer of many different kinds can increase calcium levels and accounts for about 2 out of 10 cases.

Rarer causes of hypercalcemia include:

  • Overconsumption of antacids.
  • Sarcoidosis.
  • Pulmonary tuberculosis.
  • Addison’s disease.
  • Prolonged bed rest – especially in teenagers whose bones are growing fast.
  • Vitamin A and/or D overdose.
  • A number of medicines, including lithium, tamoxifen, and diuretics.
  • Kidney dialysis.

Prothrombin time (PT) or International Normalised Ratio (INR) are sometimes measured as a part of standard liver function tests.

PT and INR are ways of measuring the ability of your blood to clot. Conditions which impair this clotting (prolonging the PT and increasing the INR) include:

  • Acute and severe liver disease (including liver failure and severe paracetamol overdose).
  • Use of anticoagulant medicines (in this case, lengthening the prothrombin time and increasing the INR is the intention).

There is a difference between what you need to do to keep your liver healthy most of the time and what you need to do if your liver is inflamed or damaged.

  • If you are well, the way to look after your liver is with a balanced diet with good fiber content, exercise, maintenance of a healthy weight, avoiding ‘fad’ diets (which can challenge the kidneys and liver hard), avoiding unnecessary medicines and supplements including paracetamol, stopping smoking, and staying within the recommended limits for alcohol (both daily and weekly). The liver does not need a detox diet, which will not help it and will often (if it is very low-calorie, for instance) make it work harder. The liver is a digesting, storage, and detoxing organ.
  • If your liver is inflamed and injured (for example, you have hepatitis and are jaundiced) or you have advanced liver disease (for example, cirrhosis) then, depending on the severity, you may be advised to have a special diet. This involves using carbohydrates as your major source of calories, eating fat moderately, and cutting down on protein. You may be advised to take vitamin supplements, and if you are retaining fluid you should reduce your salt consumption to less than 1500 milligrams per day.

A few things to remember about abnormal liver function tests

  • Liver function tests are not a diagnosis; they are a set of clues that help doctors make a diagnosis.
  • Liver function tests are a sensitive early warning system for problems in the liver and, in some cases, elsewhere.
  • Because ‘normal ranges’ used by laboratories are the levels between which about 19 out of 20 of people’s tests will fall, about 1 person in 20 will have an abnormal test without cause. About half of these people will have slightly high tests and about half will have slightly low tests, but their levels, either way, should not be extreme.
  • The most likely cause of any particular pattern of abnormal liver function tests varies between patients (because of difference in age and gender) and between populations (because of variations in genetics and because different things are more common in different parts of the world).
  • Almost any pattern of liver function test abnormality can be caused by medicines (including over-the-counter medications), by herbal remedies and traditional medicines from other cultures, and by poisonous substances.
  • Many liver conditions cause no symptoms, at least at first; so, if you have several abnormal tests (or one test is markedly abnormal), it is very important to follow this up.
  • Although single, mildly abnormal tests are not usually significant, any unexplained abnormality generally needs a check that you are well and may need a repeat test.
  • Abnormal liver function tests in a person who is also sick are more worrying than those in a person who is well.

References

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