Assessing liver function
There is no single specific method of determining a patient’s liver function. A combination of liver blood tests, causes of liver disease, and signs and symptoms of liver disease are required to estimate liver function.
When to refer
Patients with the following symptoms should be urgently referred to secondary care or A&E for follow up:
- weight loss, clinical jaundice or marked cholestasis which could be signs of liver cancer
- ascites, encephalopathy or bleeding which could be signs of liver decompensation
- jaundice, low albumin or prolonged international normalised ratio (INR) which could be signs of synthetic liver failure
- marked derangement of liver blood tests
Signs and symptoms of liver dysfunction
Signs and symptoms of liver dysfunction are useful to assess alongside liver blood tests to assist in diagnosis and prognosis.
Some patients may have no obvious signs and symptoms of liver dysfunction.
The British Liver Trust has further information on the signs and symptoms of liver disease including red flag symptoms.
Early liver dysfunction
Early non-specific symptoms might include feeling unwell, fatigue, nausea and vomiting, loss of appetite or a tenderness in the liver area.
Advanced liver dysfunction
Symptoms associated with advanced disease may include jaundice, swelling of the abdomen, confusion (encephalopathy), difficulty in stopping bleeding, pale stools, dark urine, fatty stools (steatorrhea), pruritus, and gynecomastia.
Child-Pugh score
The Child-Pugh score was originally designed to assess the severity of liver dysfunction in patients with cirrhosis. It was not developed to guide drug dosing and can only be used in patients with cirrhosis.
For further information, visit our page on calculating and using the Child-Pugh score.
Interpreting liver blood tests
Liver blood tests can be monitored over hours, days or weeks to assess whether liver function is stable, improving or deteriorating. The monitoring frequency will depend on the diagnosis.
When interpreted in isolation, the clinical significance of liver blood tests can often be unclear because:
- abnormal liver blood tests do not always indicate the extent of liver damage
- results can be normal even in advanced liver disease
- some liver blood tests can be abnormal in the absence of liver disease or affected by conditions not related to the liver
- some changes to liver blood tests are transient
Questions to ask when giving medicines advice in liver impairment provides guidance on the background information and risk factors to consider when gathering information.
Abnormal liver blood tests
Interpreting liver blood tests is complicated. In all cases, take a full medical history, including signs and symptoms of liver disease, and consider risk factors.
Consider the following factors when liver blood tests are abnormal.
Slightly abnormal
Generally, if liver blood tests are less than twice the upper limit of normal (ULN), repeat the tests and consider seeking further advice.
Refer to secondary care or a liver specialist if no cause can be identified and liver blood tests continue to be abnormal.
If the cause is alcohol-related, ask the patient to abstain, and repeat their liver blood tests after a month.
Significantly abnormal
Any level greater than 2 to 3 times the ULN requires further investigation. This may include further blood tests, imaging or referral to secondary care or a liver specialist for investigation and follow up.
Interpreting liver blood tests
Check your local reference ranges as these can vary between laboratories.
The management of abnormal liver blood tests will depend on the cause. Many medicines can also affect liver blood tests.
Below are examples of common liver blood tests and their reference ranges.
Albumin
Albumin is a protein made in the liver. It is a non-specific indicator of the synthetic function of the liver with a long half-life (20 days).
A low albumin without alteration in other liver blood tests is unlikely to be of hepatic origin.
A low albumin in association with abnormal liver blood tests can indicate chronic liver disease or dysfunction.
However, albumin can also be reduced in other clinical situations, such as sepsis, systemic inflammatory disorders, nephrotic syndrome, malabsorption, and gastrointestinal protein loss.
Normal blood albumin levels range from 35 to 50 g/L.
Abnormal results
Refer any patients with low albumin and abnormal liver blood tests to secondary care or a liver specialist for further investigation.
ALT and AST
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) transaminases are enzymes found in the liver. When the liver is damaged, ALT and AST levels can increase within hours and remain high for a few days after.
ALT and AST levels can be raised in viral hepatitis, non alcoholic fatty liver disease (now known as metabolic dysfunction-associated steatotic liver disease), alcohol related liver disease, auto-immune hepatitis and drug-induced liver injury. They can also be raised in heart disease.
Normal blood ALT and AST levels range from 0 to 40 IU/L.
Abnormal results
Marked elevations of ALT or AST (greater than 1,000 IU/L) suggest drug-induced liver injury (such as paracetamol overdose), acute viral hepatitis, ischaemic, or autoimmune hepatitis and may require referral to secondary care for further follow up.
ALP
Alkaline phosphatase (ALP) is a non-specific liver enzyme mainly found in the bile ducts of the liver.
Increases in ALP together with an elevated GGT can indicate cholestasis. ALP can also be slightly raised in hepatocellular disease such as primary biliary cholangitis, biliary obstruction and genetic disorders of bile synthesis and excretion.
High levels of ALP can also occur in bone diseases. If ALP levels are high in isolation, consider checking the patient’s vitamin D status.
Normal reference ranges depend on the assay method used. Check local laboratory reference ranges.
Abnormal results
The management plan depends on the extent of ALP elevation and abnormalities in other liver blood tests.
Bilirubin
Bilirubin is the main pigment in bile. It is produced when red blood cells are broken down in the liver.
It may be raised in cholestasis but can also be raised in hepatocellular disease.
Normal blood bilirubin levels range from 5 to 21 micromol/L.
Abnormal results
The management plan depends on the extent of bilirubin elevation and abnormalities in other liver blood tests.
GGT
Gamma glutamyl transpeptidase (GGT) is mainly found in the liver.
High GGT levels and high ALP levels are indicative of cholestasis.
GGT levels can be high from alcohol use.
GGT levels may be 2 to 3 times above the ULN in patients with non-alcoholic fatty liver disease (also called metabolic dysfunction-associated steatotic liver disease) and in patients with chronic hepatitis C infection.
Normal GGT levels range from 0 to 50 IU/L.
Abnormal results
Stopping alcohol intake for 4 weeks should normalise GGT levels in patients with excessive alcohol consumption.
Platelets
Low platelet count (thrombocytopenia) is the most common blood abnormality in chronic liver disease. However, platelets may also be reduced in a wide variety of medical conditions. See NICE CKS for information on non-cancer causes for low platelet levels.
Thrombocytopenia is a platelet count below 150 × 109/L.
Abnormal results
All patients with chronic liver disease and thrombocytopenia should be managed within secondary care.
PT
Prothrombin is a protein made by the liver to help blood clot. Prothrombin Time (PT) measures how long it takes for blood to clot.
PT is a sensitive indicator of the synthetic function of the liver, particularly in acute liver failure due to its short half-life (approximately one day) and is used to calculate INR.
An increase in PT usually results from decreased clotting factors, warfarin treatment, or deficiency in vitamin K as seen in fat malabsorption and chronic cholestasis.
A increase in PT without alteration in other liver blood tests is unlikely to be of hepatic origin.
Normal reference ranges are from 12 to 16 seconds.
Abnormal results
Any liver abnormalities with raised PT or raised INR should be referred to secondary care or a liver specialist for further investigation.
Liver blood tests and hepatotoxic medicines
Some medicines, including herbal and dietary supplements, can cause mild, transient, and insignificant increases in liver blood tests but this may not be an absolute contraindication in patients with liver dysfunction.
The risks and benefits of using the medicine need to be considered, although the interpretation of liver blood tests and monitoring over the course of a patient’s liver disease may become more complicated.
The SPS medicines monitoring tool provides monitoring advice for specific medicines including liver function.
Further information and support
Information resources for managing medicines in liver impairment signposts to other good sources of information.
Patient.info provides further and more detailed information on liver blood tests, what to do when abnormal and non-hepatic, hepatocellular and cholestatic patterns of abnormality. It is recommended to read these resources in addition to this article.
If relevant information is not available on the SPS website or the information resources listed, or if your clinical scenario is complex, we suggest you seek further advice from the SPS Medicines Advice service.