Interpretation of Liver Function Tests (LFTs)

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Liver function tests (LFTs) are among the most commonly ordered blood tests and include:

  • Alanine transaminase (ALT)
  • Aspartate aminotransferase (AST)
  • Alkaline phosphatase (ALP)
  • Gamma-glutamyltransferase  (GGT)
  • Bilirubin
  • Albumin

This guide gives an overview of LFTs and a structured approach to their interpretation.

Why check LFTs?

LFTs can be requested for multiple reasons:1

  • To investigate patients with suspected liver disease
  • To monitor patients with confirmed liver disease (e.g. cirrhosis)
  • To monitor the effects of potentially hepatotoxic medications

LFTs are often sent as part of a ‘baseline’ screening panel of investigations for patients presenting with a wide range of symptoms, even where none of the above criteria is met. 

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Reference ranges

Table 1. Liver function test reference ranges

Test Reference range
ALT 3-40 IU/L
AST 3-30 IU/L
ALP 30-100 IU/L
GGT 8-60 IU/L
Bilirubin 3-17 μmol/L
Albumin 35-50 g/L

These reference ranges can vary between laboratories, so always check local guidelines. 


Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes found within liver cells at high concentrations.

Raised ALT / AST levels in the blood occur in pathologies that cause liver cell (hepatocyte) inflammation or damage. Therefore, raised ALT / AST levels are a marker of hepatocellular injury.

Common causes of hepatocellular injury include:

  • Hepatitis (viral, alcoholic, ischaemic)
  • Liver cirrhosis
  • Drug / toxin-induced liver injury (e.g. paracetamol overdose)
  • Malignancy (hepatocellular carcinoma)

Hint: The AST:ALT ratio can help determine the aetiology of hepatocellular injury, with a >2:1 ratio classical of alcoholic liver disease.2


Serum alkaline phosphatase (ALP) is derived from biliary epithelial cells (cells lining the biliary tract) and bones.3 Raised ALP levels can therefore be caused by cholestasis or bone disease.


Cholestasis describes an interruption in the bile flow from hepatocytes to the small intestine. Common causes include gallstone disease, external compression of the biliary tract (e.g. pancreatic malignancy) or medication side effects. Bilirubin may or may not be raised depending on the severity of cholestasis.

Gamma-glutamyltransferase (GGT) is found in hepatocytes and also biliary epithelial cells.2 It is a non-specific but highly sensitive marker of liver damage and cholestasis.

ALP and GGT are interpreted together to localise the source of raised ALP in the blood:

  • An ALP rise with normal GGT suggests bone disease (e.g. Paget’s disease, vitamin D deficiency, bony metastases)
  • An ALP rise with associated GGT rise is more suggestive of cholestasis

Hint: An isolated GGT rise is classically associated with alcohol excess.


Bilirubin is a waste product of haemoglobin breakdown. It is predominantly metabolised and excreted by the liver. Raised levels of bilirubin in the blood will lead to a yellowing of the skin, known as jaundice.

Hint: Jaundice is usually absent until the bilirubin level exceeds 50 micromol/L.

Bilirubin metabolism

To understand the significance of raised bilirubin levels, it is essential to consider the bilirubin metabolism/excretion pathway:4

  • When red blood cells are broken down, unconjugated (insoluble) bilirubin is created as a waste product and binds to albumin in the bloodstream
  • Hepatocytes take up unconjugated bilirubin and metabolise it to form conjugated (soluble) bilirubin
  • Hepatocytes excrete conjugated bilirubin into the biliary tract, where it flows into the bowel lumen as bile
  • Gut bacteria further metabolise bilirubin in bile to form urobilinogen, which is eventually excreted in the stools as stercobilinogen
  • A small amount of urobilinogen is reabsorbed from the intestine into the portal venous system, and as urobilinogen is water-soluble, the kidney is able to excrete some of this into the urine.

Stercobilinogen gives stools their dark colour. Urobilinogen is colourless in the urine. However, if the urine is left exposed to the air, oxidation will occur, creating a dark colour. Under normal physiological conditions, urobilinogen will be present in the urine, however conjugated bilirubin will not be present.

Raised levels of bilirubin in the blood can be caused by:

  • Excess bilirubin production (pre-hepatic jaundice)
  • A breakdown in bilirubin metabolism (hepatocellular jaundice)
  • A blockage in the bile excretion pathway (cholestatic jaundice)

Pre-hepatic jaundice

Pre-hepatic jaundice occurs when increased red blood cell breakdown produces excess bilirubin. This can overwhelm metabolism/excretion pathways, leading to jaundice.

The most common cause of increased red blood cell breakdown is haemolysis. Bilirubin is unconjugated in the blood, as the hepatocytes have not yet metabolised it. The remainder of LFTs are generally normal, as the liver is otherwise working well.

Hint: In pre-hepatic jaundice, patients are often anaemic due to excess red blood cell breakdown. The diagnosis may be Gilbert’s syndrome if no anaemia is present.

Gilbert’s syndrome

Gilbert’s syndrome is a congenital disorder present in up to 5% of the population. It results from a deficiency of glucosyltransferase, the enzyme responsible for the conjugation of bilirubin within hepatocytes.

Gilbert’s syndrome classically presents following viral infection with raised bilirubin but normal LFTs/ full blood count. The disease is benign and requires no specific management.

Hepatocellular jaundice

Hepatocellular jaundice occurs when hepatocytes are damaged and dysfunctional, leading to an inability to metabolise unconjugated bilirubin from the bloodstream. This leads to high levels of unconjugated bilirubin in the blood. There will generally also be very high ALT / AST levels, marking hepatocyte damage.

Hint: Common causes of hepatocellular injury are covered above (hepatitis, cirrhosis, malignancy, drug or toxin insult). When liver injury is severe, there are not enough functioning hepatocytes to metabolise bilirubin, and jaundice will develop.

Cholestatic (obstructive) jaundice

Cholestasis is an interruption in bile flow from hepatocytes to the gut. When this interruption is severe, bilirubin levels will build up in the blood. The bilirubin has been metabolised in the liver, and thus the bilirubin in the blood is predominantly conjugated bilirubin. There will generally also be high ALP levels with associated high GGT, marking dysfunction of the biliary system.

Obstructive jaundice will classically lead to dark urine and pale stools. Bilirubin cannot enter the gastrointestinal tract due to cholestasis, leading to low stercobilinogen excretion in stools.

The bilirubin in the blood is conjugated and can be filtered by the kidneys. The presence of conjugated bilirubin gives the urine a very dark colour.

Hint: Stools may also be pale in hepatocellular jaundice, as there is decreased bilirubin metabolism/excretion, however as the bilirubin in the blood is unconjugated, it will not be able to pass into the urine. Therefore, the urine should remain a normal colour.

Causes of cholestasis

Cholestasis can occur due to either intrahepatic or extrahepatic biliary obstruction.

Causes of intrahepatic obstruction (obstruction of the hepatic bile canaliculi):

  • Hepatitis
  • Cirrhosis
  • Malignancy
  • Drugs (e.g. antibiotics, oral contraceptive pills, anabolic steroids)
  • Pregnancy

Causes of extrahepatic obstruction (obstruction of hepatic ducts, or distal biliary tree):

Split bilirubin

The split of conjugated/unconjugated bilirubin in the blood can be requested to give further clues as to the aetiology of jaundice.

Causes of predominantly unconjugated hyperbilirubinaemia:

  • Pre-hepatic jaundice (e.g. haemolysis)
  • Gilbert syndrome

Causes of predominantly conjugated hyperbilirubinaemia:

  • Cholestasis
  • Hepatocellular jaundice*

*Hepatocellular jaundice can initially cause a mixed conjugated/unconjugated jaundice, but at its most severe, unconjugated hyperbilirubinaemia is seen.


Albumin is synthesised in the liver and helps to bind water, cations, fatty acids and bilirubin. It also plays a crucial role in maintaining the oncotic pressure of blood. Albumin is used as a non-specific marker of the synthetic function of the liver.

Albumin levels can fall due to:

Hint: A decrease in the synthetic function of the liver indicates severe liver disease.

Albumin has a half-life of 20 days, so it will take time to decrease, even in severe liver disease. Further assessment of the synthetic function of the liver can be gained by ordering a coagulation screen, as the liver is also responsible for the synthesis of clotting factors.

Severe liver disease leads to decreased production of clotting factors and an increased prothrombin time (PT) / INR in the absence of other causes of coagulopathy.

The liver is also responsible for gluconeogenesis, and serum blood glucose assessment can also indirectly assess the liver’s synthetic function. However, gluconeogenesis tends to be one of the last functions to become impaired in liver failure.

LFT interpretation method

Determine the pattern of LFT derangement

The pattern of ALT to ALP rise can indicate whether the pathology is primarily cholestatic or hepatocellular:

  • A greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular injury
  • A less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis
  • It is possible to have a mixed picture involving both hepatocellular injury and cholestasis

An isolated ALP rise without a GGT rise should raise your suspicion of bony pathology.

Assess the bilirubin

Bilirubin is a marker of severity in acute cholestatic pathology and acute hepatocellular liver injuries. The presence of clinical jaundice is generally an indication of severe disease requiring urgent referral to secondary care for prompt assessment and management.

An isolated bilirubin rise without further LFT derangement suggests pre-hepatic jaundice or Gilbert’s disease.

Assess synthetic function

In severe hepatocellular injuries, the synthetic functions of the liver also become impaired, leading to decreased albumin.

Coagulation studies may show prolonged prothrombin time, and in very severe disease, serum blood glucose may be low due to impaired gluconeogenesis.

Hint: In chronic hepatocellular pathology (e.g. cirrhosis), the ALT / AST may return to within the normal range, however synthetic function of the liver can be markedly impaired.

Summary table

The table below compares the typical LFT patterns associated with acute hepatocellular damage and cholestasis. A single arrow (↑) refers to a mild impairment, and a double arrow (↑↑) refers to severe impairment.

  Acute hepatocellular damage Cholestasis



Normal or ↑



Normal or ↑


 Normal or ↑



 Normal or ↑



 Range from normal to ↑↑

 Range from normal to ↑↑

Further investigations

Once the pattern of LFT derangement has been established, it is essential to determine the underlying cause.

If cholestasis is suspected, an ultrasound should be arranged to assess the biliary tree for a potential site/cause of biliary obstruction.

If hepatocellular injury is suspected, a liver ultrasound is generally arranged to assess for any structural lesions that may give clues as to the diagnosis. If the cause is unclear, a ‘liver screen’ may be ordered to investigate further.

Liver screen

A ‘liver screen’ is a batch of blood investigations to identify a wide range of potential causes of liver disease:

  • Hepatitis serology (A/B/C)
  • Epstein-Barr Virus (EBV)
  • Cytomegalovirus (CMV)
  • Anti-mitochondrial antibody (AMA)
  • Anti-smooth muscle antibody (ASMA)
  • Anti-liver/kidney microsomal antibodies (Anti-LKM)
  • Anti-nuclear antibody (ANA)
  • p-ANCA
  • Immunoglobulins – IgM/IgG
  • Alpha-1 Antitrypsin (to rule out alpha-1 antitrypsin deficiency)
  • Serum Copper (to rule out Wilson’s disease)
  • Ceruloplasmin (to rule out Wilson’s disease)
  • Ferritin (to rule out haemochromatosis)


Dr Chris Jefferies


  1. Coates P. Liver Function Tests. Australian Family Physician. March 2011. Available at [LINK].
  2. UpToDate. Approach to the patient with abnormal liver biochemical and function tests. May 2023. Available at [LINK].
  3. Professional. Abnormal Liver Function Tests. July 2019. Available at [LINK].
  4. UpToDate. Bilirubin metabolism. October 2022. Available at [LINK].


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