GPAtlas🧭 When to suspect
Jaundice is the visible yellowing of the sclerae and skin produced by accumulation of bilirubin. It is a clinical sign, not a diagnosis, and the task in primary care is to establish the mechanism and, above all, to identify the few causes that are immediately dangerous. Jaundice becomes visible once the serum bilirubin reaches roughly 50 µmol/L (normal is about 3–20 µmol/L); it appears earliest in the sclerae and is easily overlooked in people with brown or black skin, so examine the eyes in good natural light.
The single most useful discriminator is the pattern of the liver enzymes alongside the colour of the urine and stool. A hepatocellular picture (alanine and aspartate aminotransferases – ALT and AST – raised disproportionately) points to intrinsic liver disease, whereas a cholestatic picture (alkaline phosphatase – ALP – and gamma-glutamyl transferase – GGT – raised disproportionately) points to obstruction. Conjugated (water-soluble) hyperbilirubinaemia spills into the urine and is blocked from the gut, producing the classic triad of dark urine, pale stools and pruritus; unconjugated (pre-hepatic) hyperbilirubinaemia does not.
| Mechanism | Blood-test & clinical clues | Common causes |
|---|---|---|
| Pre-hepatic | Unconjugated (indirect) hyperbilirubinaemia; ALT/ALP normal; urine and stool normal; no pruritus | Haemolysis; Gilbert's syndrome; resorption of a large haematoma |
| Hepatocellular | Mixed/conjugated; ALT and AST raised > ALP; may show stigmata of chronic liver disease | Viral hepatitis (A, B, C, E); alcohol-related and metabolic-associated liver disease; drug-induced liver injury; autoimmune hepatitis; cirrhosis |
| Cholestatic / obstructive | Conjugated; ALP and GGT raised > ALT; dark urine, pale stools, pruritus | Common bile duct stones; pancreatic / biliary malignancy; primary biliary cholangitis and primary sclerosing cholangitis; drug-induced cholestasis |
Treat painless jaundice with weight loss, particularly over the age of 40, as malignancy until proven otherwise; treat fever with right upper quadrant (RUQ) pain and jaundice as ascending cholangitis; and treat confusion, bruising or rapidly deepening jaundice as acute liver failure.
Source: NICE NG12 · British Society of Gastroenterology
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