Ask three questions of every set of results. One: is the bilirubin conjugated or unconjugated? Two: is the enzyme rise hepatocellular (ALT dominant) or cholestatic (ALP and GGT dominant)? Three: is the liver still working (INR and albumin)? Most of what people call "liver function tests" are actually markers of liver injury. Only bilirubin, albumin and the INR say anything about function.
The three patterns
| Unconjugated haemolysis · Gilbert |
Hepatocellular hepatitis · drugs · ischaemia |
Cholestatic stones · tumour · drug cholestasis | |
|---|---|---|---|
| Bilirubin | Unconjugated | Mixed | Conjugated |
| ALT / AST | Normal | ↑↑↑ (may exceed 1000 U/L) | Normal or mildly ↑ |
| ALP / GGT | Normal | Normal or mildly ↑ | ↑↑↑ |
| Albumin | Normal | Normal; ↓ if chronic | Normal early |
| INR | Normal | ↑ if failing; usually not corrected by vitamin K | May ↑; usually corrects with vitamin K |
| Urine | No bilirubin; urobilinogen ↑ | Bilirubin + | Bilirubin +; urobilinogen absent if complete |
| Next step | Blood film, reticulocytes, LDH, haptoglobin, Coombs, G6PD | Viral serology, paracetamol level, drug review | Ultrasound — are the ducts dilated? |
What each test actually measures
| Test | Reflects | How to read it |
|---|---|---|
| Bilirubin | Production versus clearance | Confirms and grades jaundice. The height alone does not tell you the cause; the pattern of the others does. |
| ALT | Hepatocyte injury (liver-specific) | Dominant rise means a hepatocellular picture. |
| AST | Injury: liver, muscle, heart, red cells | An AST:ALT ratio above 2 suggests alcohol. Also rises in haemolysis and muscle injury. |
| ALP | Bile duct epithelium; also bone and placenta | Dominant rise means cholestasis — but check GGT to confirm it is coming from the liver. |
| GGT | Biliary epithelium; enzyme induction | Rises with ALP in cholestasis. An isolated rise suggests alcohol or enzyme-inducing drugs. |
| Albumin | Synthetic function, slow (half-life ≈3 weeks) | Low in chronic liver disease — but also in sepsis, malnutrition and nephrotic syndrome. |
| PT / INR | Synthetic function, fast (factor VII, hours) | The best early marker in acute liver failure. Also rises with vitamin K malabsorption in obstruction. |
The R-factor: a number instead of an argument
"Which enzyme is higher?" is not a fair question when the reference ranges differ. The R-factor normalises both to their upper limit of normal first:
R = (ALT ÷ ULN of ALT) ÷ (ALP ÷ ULN of ALP)
- R ≥ 5 — hepatocellular
- R between 2 and 5 — mixed
- R ≤ 2 — cholestatic
Use the free R-factor calculator to work it out with your own laboratory's limits.
ALT above 1000 U/L — a short list
Viral hepatitis (A, B, E) · paracetamol and other drug toxicity · ischaemic "shock liver" after hypotension · acute autoimmune hepatitis · a passing common bile duct stone. Surgeons meet the last one often: a patient with biliary pain whose ALT is 1200 on day one and 300 on day three has usually passed a stone, not caught hepatitis. The trend over 48–72 hours is more informative than any single set.
Five traps
- CA 19-9 rises in any biliary obstruction, benign or malignant, and in cholangitis. It cannot diagnose cancer on its own — repeat it after drainage.
- Bilirubin falls slowly after successful drainage, because part of it is bound to albumin (delta bilirubin) and clears over two to three weeks. A slow fall is not a failed stent if the patient and the ALP are improving.
- Falling ALT with a rising INR in acute hepatitis can mean hepatocytes are running out, not recovering.
- Isolated high ALP with a normal GGT is usually bone — a growing adolescent, fractures, Paget's disease, metastases — or pregnancy.
- Isolated unconjugated bilirubin with a normal blood count, normal reticulocytes and normal enzymes is Gilbert syndrome. Reassure; no scan needed.
A note on reference ranges
Ranges differ between laboratories. The examples on this site use ALT 0–41 U/L, AST 0–40, ALP 35–105, GGT 5–36, albumin 3.8–4.4 g/dL and total bilirubin 0.0–1.1 mg/dL with a direct fraction up to 0.3. Always read results against the ranges printed on your own report.