Understanding blood results: Liver function test

The liver function test is another commonly requested test in primary care, and as part of our occasional series, this article aims to increase understanding and confidence in nurses involved in taking blood samples and reviewing test results

Liver diseases are common, and although liver function tests (LFTs) are critical in recognising the presence of liver disease, the interpretation of test results may be confusing and difficult, and it is not uncommon for abnormal results to be found in patients who do not have liver disease.¹

PREVALENCE OF LIVER DISEASE

Chronic liver disease is of concern because of its impact on physical well being and quality of life, and of course its association with morbidity and mortality. There is concern that deaths from liver disease appear to be rising, and while there are many causes of liver disease, statistics indicates that the incidence of all types is increasing with approximately 7, 500 deaths each year in the U.K alone.² Rising levels of alcohol consumption have become a growing area of concern, and in the past fifteen years UK alcohol-related deaths have doubled with increased mortality reported in both sexes and across all age groups.³ A study conducted in 2004 confirmed rising hospitalisation rates for all forms of liver disease but for cirrhosis particularly, with higher rates in males, and the greatest number of admissions in the age groups 55-64, followed by those aged 45-54.²

THE HEALTHY LIVER

The liver is the largest internal organ in the body. It is believed to be responsible for approximately five hundred functions all of which are vital to maintaining health. A highly complex organ with many functions, it has the ability to affect other organs and processes when the liver itself organ is functioning ineffectively. Table 1 shows some of its most important functions.

The liver is made up of two lobes, separated by the entry of the major blood vessels and also by the falciform ligament. The majority of cells found in the liver are hepatocytes, and they are responsible for carrying out the majority of the functions performed by the liver. Groups of hepatocytes are gathered together in clusters to form lobules, and it is estimated that the liver contains approximately a million of these.

The blood supply is complex, and unlike other organs, the majority of the blood supply to the liver is venous blood, via the hepatic portal vein, which contains both nutrients and toxins from the gastrointestinal tract. Oxygenated blood is supplied via the hepatic artery. Waste substances in the liver are broken down and excreted either into bile for removal in the faeces, or into the bloodstream for removal via the kidneys.

WHEN ARE LFTs REQUESTED?

he test may be requested for a number of reasons, including screening for suspected liver problems, to monitor patients with known liver disease or to assess the effect of any medications which are known to potentially affect liver function. They may also be used to assess the severity and predict the outcome of certain diseases such as primary biliary cirrhosis.⁴

Signs and symptoms

In healthy adults, the liver is thought to continue to function well into old age. Even patients found to have abnormal liver function tests may be asymptomatic, the problem often detected as an incidental finding. Physical examination may also be normal unless the liver is grossly enlarged. A careful history may help to identify a cause for an abnormal result - for example, excessive alcohol intake or intravenous drug use. However, what makes liver function tests confusing is the fact that abnormalities may be a result of problems elsewhere in the body.⁵ Some of the most common causes of abnormal liver function tests are shown in Table 2. Any symptoms present are highly variable and depend on the underlying cause and the severity of liver damage. Common signs and symptoms of liver damage include jaundice, fatigue, nausea, vomiting, dark urine, pale coloured stools, itching, and ascites.

Measurements and normal values

When results are reported individual parameters are shown alongside the reference range. Reference ranges are derived by testing large numbers of healthy people and then observing what appears to be normal for them.⁶ Table 3 shows the normal values.

An abnormal level is usually defined as a value exceeding the upper reference limit - with liver function tests there is no clinical significance of low levels of biochemical markers with the exception of albumin.⁷

TESTS AND INTERPRETATION

Alanine aminotransferase (ALT)

Alanine aminotransferase (ALT) is a sensitive indicator of liver cell injury, and levels can be modestly increased as a result of any type of liver cell damage.⁸ ALT is considered - alongside aspartate aminotransferase (AST), as the two go hand in hand - as indicators of hepatocyte malfunction. ALT is more specific for liver damage since it is found primarily in the liver and has a longer half-life, whereas AST is found in many other organs.⁵ The level of ALT guides the clinician to the need for further investigation and the urgency with which this should be undertaken. A serum level less than five times the upper limit of normal should be reassessed before further intervention is considered.

Aspartate aminotransferase (AST)

AST is an enzyme found primarily in the liver and the heart, but it is not specific to these two organs. It is also found in the kidney, brain, pancreas, muscle tissue and red blood cells.⁴ Damage to any of these organs, or the process of haemolysis, results in the release of the enzyme into the blood stream which is then reflected by elevated blood levels. Because AST has a high level of activity in muscle, elevated levels can also arise as a result of damage to cardiac or skeletal muscle and although detected on the liver function test, in this instance the cause is unrelated to liver function

Table 4 shows some of the causes of abnormal ALT and AST levels.

AST:ALT ratio

The ratio of AST to ALT can be useful in determining the presence of alcohol-induced liver disease, which is indicated when the ratio of AST: ALT is greater than two.⁴ Both ALT and AST are dependent on vitamin B6 and when liver function tests are undertaken, B6 levels should be adequate for results to be accurate. When B6 levels are depleted, AST and ALT levels may be artificially low.⁹

Alkaline phosphatase

Alkaline phosphatase originates from two sources, liver and bone.⁵ Abnormal levels are potentially indicative of disease originating from either of these two sites. To help determine the underlying source of the problem it may be useful to request a gamma GT test as this is raised in liver disease but not in bone diseases.⁵ When bone disease has been excluded, an elevation suggests either biliary obstruction, injury to the bile duct epithelium, or reduced bile formation of flow.¹¹ When biliary obstruction occurs, levels may not rise for several days, and decrease slowly when the obstruction resolves.⁷

Gamma glutamyl transferase

Gamma glutaryl transferase or gamma GT (GGT) is an enzyme found in a variety of cells, incuding those of the pancreas, intestine, renal tubules as well as the liver hepatocytes and the biliary epithelial cells. The test is often used to screen for chronic alcohol abuse (it will be elevated in about 75% of chronic drinkers)¹¹ or may be used to monitor improvement in liver function in those receiving treatment for an alcoholic liver disease. A gamma GT level of twice the normal level is highly suggestive of alcohol abuse, however it is not specific to alcohol and may be raised in a number of non-liver diseases, including renal failure, chronic obstructive lung disease (COPD) or following acute myocardial infarction.⁵

Bilirubin

Bilirubin is formed from the breakdown of haemoglobin by the liver. Before it can be excreted into bile for elimination, it has to be converted to a water-soluble substance, conjugated bilirubin. Serum levels of conjugated bilirubin do not rise until the liver has lost at least half of its excretory capacity.⁷ In healthy individuals excretion of conjugated bilirubin into bile is rapid, so little is detectable in the urine, however in liver disease the secretion of conjugated bilirubin into the bile is impaired which results in a rapid filtration into the urine where it can be detected on urinalysis.¹² When the bilirubin levels rise significantly, infiltration into the sclera of the eyes, the skin and mucous membranes occurs, resulting in jaundice.

Albumin

Albumin is a plasma protein synthesised in the liver and secreted daily, and in progressive liver disease serum albumin levels fall, reflecting decreased synthesis.⁵ When synthesis is impaired the liver is able to compensate by increasing synthesis to twice the basal rate. There are several causes of low albumin levels, including kidney damage, inflammation, malnutrition or conditions associated with impaired protein absorption such as Crohn's disease or coeliac disease.¹³

SPECIALIST REFERRAL

Referral is needed for further investigation when parameters are grossly abnormal, or when abnormalities persist at more than 1.⁵ times the normal limit on two occasions, a minimum of six months apart.⁵ Consideration should also be given to referral of asymptomatic patient with abnormal results because many if not most patients with chronic liver disease have no symptoms or non specific symptoms.¹⁴

LIMITATIONS OF LFTs

One of the concerns relating to liver function tests is that it lacks sensitivity because results can remain normal in certain liver diseases, (such as cirrhosis) and lacks specificity because results are not specific for any particular disease and be altered by abnormalities outside of the liver.⁴

CONCLUSION

Evaluating liver function tests results is clearly a complex task, and there are now many practice nurses who undertake this as part of their role. It is always useful to understand the parameters under scrutiny and by just highlighting any abnormalities and discussing them with the GP will reap rewards in ensuring that further evaluation and follow up and, if deemed necessary, specialist referral for further investigation take place.

REFERENCES

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2. The Foundation for Liver disease. Liver disease in the UK. 2012. http://www.liver-research.org.uk/liver-foundation/institute-of-hepatology.html

3. Jackson P, Gleeson D. Alcoholic Liver Disease. Continuing Education in Anaesthesia. Critical Care and Pain 2010;10:66-71.

4. Thapa BR, Walia A. Liver function tests and their interpretation. Indian Journal of Paediatrics 2007;74:663-671

5. Limdi JK Hyde GM. Evaluation of abnormal liver function tests Postgraduate Medicine 2003;79:307-312

6. American Association for Clinical Chemistry Reference ranges and what they mean. 2010. http://labtestsonline.org/understanding/features/ref-ranges/start/1

7. Giannini EG, Testa R, Savarino V. Liver enzyme alteration a guide for clinicians Can Med Assoc J 2005;172:367-79

8. Orlewicz MS. Alanine aminotransferase. 2012. Medscape Reference Online http://emedicine.medscape.com/article/2087247-overview#showall

9. Devaraj S. Aspartate aminotranseferase. 2012 Medscape Reference Onlinehttp://emedicine.medscape.com/article/2087224-overview#showall

10. Aragon G, Younossi ZM. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleveland Clinic J Med 2010;77:195-204

11. American Association for Clinical Chemistry. GGT. 2010 http://labtestsonline.org/understanding/analytes/ggt/tab/

12. Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician 1999;59:2223-2230.

13. American Association for Clinical Chemistry Albumin. 2010 Lab tests online http://www.labtestsonline.org.uk/understanding/analytes/albumin/tab/test

14. George GK, Ryder S, Collier J, et al. Management of abnormal liver function tests in asymptomatic patients. British Society of Gastroenterology 2005. www.bsg.org.uk/pdf_word_docs/ablft_draft05.doc