A Liver Function Test (LFT) is a blood test used to evaluate the health of the liver by measuring various enzymes, proteins, and substances produced by the liver. These tests help detect liver damage, infections, and metabolic disorders.
Key Components of LFT
- Alanine Aminotransferase (ALT) & Aspartate Aminotransferase (AST): Indicators of liver cell damage.
- Alkaline Phosphatase (ALP): Helps assess bile duct function.
- Bilirubin: Measures liver’s ability to process waste.
- Albumin & Total Protein: Evaluates liver’s protein production.
- Prothrombin Time (PT): Assesses blood clotting ability.
LFTs are commonly used to diagnose liver diseases, monitor medication effects, and assess overall liver function.
Bilirubin Metabolism
To understand the significance of raised bilirubin levels, it is essential to consider the bilirubin metabolism/excretion pathway:
- 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)
Key Liver Function Tests and Their Interpretation
1.Alanine Aminotransferase (ALT) & Aspartate Aminotransferase (AST)
Function: These enzymes are found in liver cells and indicate hepatocellular injury when elevated.
Interpretation:
- High ALT & AST: Suggests liver cell damage (e.g., viral hepatitis, alcohol-related liver disease, drug toxicity).
- AST:ALT Ratio >2:1: Often seen in alcoholic liver disease.
2.Alkaline Phosphatase (ALP) & Gamma-Glutamyl Transferase (GGT)
Function: ALP is found in bile ducts and bones, while GGT is more specific to liver and bile duct function.
Interpretation:
- Elevated ALP & GGT: Indicates cholestasis (bile flow obstruction), possibly due to gallstones or liver disease.
- High ALP with Normal GGT: May suggest bone disease rather than liver dysfunction.
3.Bilirubin Levels
Function: Bilirubin is a waste product processed by the liver and excreted in bile.
Interpretation:
- High Bilirubin: Can indicate liver dysfunction, bile duct obstruction, or hemolysis (excessive breakdown of red blood cells).
4.Albumin & Total Protein
Function: The liver synthesizes albumin, which helps maintain blood volume and transport substances.
Interpretation:
- Low Albumin: Suggests chronic liver disease, malnutrition, or kidney dysfunction.
5.Prothrombin Time (PT) & International Normalized Ratio (INR)
Function: Measures blood clotting ability, which depends on liver-produced clotting factors.
Interpretation:
- Prolonged PT/INR: Indicates impaired liver function, often seen in cirrhosis or acute liver failure.
Clinical Applications
- Assessing Drug Toxicity: Some medications can affect liver enzymes, requiring regular monitoring
- Screening for Liver Disease: LFTs help detect conditions like hepatitis, fatty liver disease, and cirrhosis.
- Monitoring Liver Function: Used to track disease progression or response to treatment.
Varying Reference Ranges
When assessing your patient’s bloodwork, it’s important to remember that reference ranges will vary by laboratory. In addition, certain ranges will differ between males and females and may be higher in individuals with an increased body mass index.
| Liver Test (Friedman, 2022a) | General Range |
| Liver Enzymes: found in the liver and other tissues; elevated levels indicate liver injury and disease. | |
| Alanine aminotransferase (ALT) | Male: 29–33 units/Liter (L) Female: 19–25 units/L |
| Aspartate aminotransferase (AST) | Male: 10–40 units/L Female: 9–32 units/L |
| Alkaline phosphatase (ALP) | Male: 45–115 units/L Female: 30–100 units/L |
| Gamma-glutamyl transpeptidase (GGT) | Male: 8–61 units/L Female: 5–36 units/L |
| 5’-nucleotidase (Friedman, 2022b) | 0.3–3.2 Bodansky units |
| Lactate dehydrogenase (LDH) (UpToDate, n.d.) | 80–225 units/L |
| Liver Function Tests (LFTs): indication of hepatic function, the ability to produce protein as well as fibrinogen and vitamin K-dependent clotting factors II (prothrombin), VII, IX, and X. | |
| Total protein (UpToDate, n.d.) | 5.5–9.0 g/100 mL (55–90 g/L) |
| Albumin | 3.5–5 g/100 mL (35–50 g/L) |
| Prothrombin time (PT) | 11.0–13.7 seconds |
| International normalized ratio (INR) (Shikdar, Vashisht, & Bhattacharya, 2023) | Approximately 1.0 second |
| Bilirubin: the pigment in bile produced from the breakdown of blood proteins (hemoglobin) in aging red blood cells. Levels will indicate bile duct injury or obstruction. | |
| Bilirubin, total (UpToDate, n.d.) | 0.3–1.0 mg/dL (5.1–17.1 mmol/L) |
| Direct bilirubin, conjugated (UpToDate, n.d.) | 0.1–0.3 mg/dL (1.7–5.1 mmol/L) |
| Indirect bilirubin, unconjugated (UpToDate, n.d.) | 0.2–0.7 mg/dL (3.4–12 mmol/L) |
Degree of elevation
The degree of elevation will vary depending on the cause of injury.
- Borderline: AST and/or ALT elevation is less than 2 times the upper limit of normal (ULN).
- Mild: AST and/or ALT elevation is 2 to 5 times the ULN.
- Moderate: AST and/or ALT elevation is 5 to 15 times the ULN.
- Severe: AST and/or ALT elevation is greater than 15 times the ULN.
- Massive: AST and/or ALT is greater than 10,000 units/L.
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)
REFERENCES
- Friedman, L.S. (2022a, April 5). Approach to the patient with abnormal liver biochemical and function tests. UpToDate. https://www.uptodate.com/contents/approach-to-the-patient-with-abnormal-liver-biochemical-and-function-tests
- Friedman, L.S. (2022b, July 28). Enzymatic measures of cholestasis (e.g., alkaline phosphatase, 5’-nucleotidase, gamma-glutamyl transpeptidase). UpToDate. https://www.uptodate.com/contents/enzymatic-measures-of-cholestasis-eg-alkaline-phosphatase-5-nucleotidase-gamma-glutamyl-transpeptidase
- Lala, V., Zubair, M. & Minter, D.A. (2023, July 30). Liver Function Tests. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482489
- Malakouti, M., Kataria, A., Ali, S. K., & Schenker, S. (2017). Elevated Liver Enzymes in Asymptomatic Patients – What Should I Do?. Journal of clinical and translational hepatology, 5(4), 394–403. https://doi.org/10.14218/JCTH.2017.00027
- Melendez-Rosado, J., Alsaad, A., Stancampiano, F. F., & Palmer, W. C. (2018). Abnormal Liver Enzymes. Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates, 41(6), 497–507. https://doi.org/10.1097/SGA.0000000000000346
- Saiman, Y. (2023, August). Laboratory Tests of the Liver and Gallbladder. Merck Manual. https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/testing-for-hepatic-and-biliary-disorders/laboratory-tests-of-the-liver-and-gallbladder
- Shikdar, S., Vashisht, R., & Bhattacharya, P. (2023, May 1). International Normalized Ratio (INR). Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK507707/
- UpToDate. (n.d.) Laboratory test reference ranges in adults. UpToDate. https://www.uptodate.com/contents/laboratory-test-reference-ranges-in-adults
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