Jaundice in adults

Adult jaundice (icterus) is yellow discoloration of the sclerae, skin, and mucous membranes caused by hyperbilirubinaemia. In UK practice, bilirubin is normally <21 micromol/L and visible jaundice usually appears once bilirubin rises to around >50 micromol/L, so jaundice should be treated as a clinical sign that requires cause-directed assessment rather than a diagnosis on its own.

Bilirubin handling has three linked stages, and failure at any stage can produce jaundice. In pre-hepatic disease, excess haem breakdown (usually haemolysis) generates unconjugated bilirubin faster than hepatocytes can conjugate it; this form is albumin-bound, water-insoluble, and not excreted in urine. In intra-hepatic disease, hepatocyte uptake/conjugation/excretion is impaired by inflammation, toxins, alcohol, MASLD, autoimmune disease, hereditary disorders, or infiltrative malignancy, often giving mixed patterns of bilirubin and liver enzyme derangement. In post-hepatic disease, conjugated bilirubin cannot drain through bile ducts (for example gallstones, strictures, pancreatic or biliary malignancy), causing cholestasis with dark urine and pale stool. Mechanisms frequently overlap in real patients (for example sepsis with cholestasis plus drug injury). See Figure: bilirubin metabolism pathway (standard hepatology textbook diagram of pre-hepatic, hepatic, and post-hepatic flow).

• Gallstone disease
• Alcohol misuse
• Viral hepatitis exposure risk (blood-borne or sexual)
• Metabolic dysfunction-associated steatotic liver disease (obesity, type 2 diabetes, dyslipidaemia)
• Known autoimmune disease (for autoimmune hepatitis or cholangiopathy)
• Personal or family history of inherited haemolytic disorders (for example sickle cell disease, thalassaemia, hereditary spherocytosis, G6PD deficiency)
• Recent or chronic hepatotoxic drug exposure (for example paracetamol excess, amoxicillin-clavulanate, flucloxacillin, nitrofurantoin, isoniazid, rifampicin, terbinafine, chlorpromazine, antiepileptics)
• Use of herbal/dietary supplements or anabolic steroids
• Increasing age and comorbidity (higher risk of idiosyncratic DILI and malignancy)
• Pancreatic or biliary tract cancer risk factors (age, smoking, chronic pancreatitis)

• Ascending cholangitis with sepsis and shock
• Acute liver failure with encephalopathy and coagulopathy
• Progressive chronic liver disease, portal hypertension, and hepatic decompensation
• Renal dysfunction (including hepatorenal syndrome in advanced liver disease)
• Fat-soluble vitamin deficiency and malnutrition in prolonged cholestasis
• Missed or delayed diagnosis of pancreatobiliary or hepatic malignancy

Prognosis is determined by the underlying cause and speed of intervention: benign inherited conditions (for example Gilbert syndrome) have an excellent outlook, whereas obstructive sepsis, acute severe DILI, and hepatopancreatobiliary cancers carry substantial morbidity and mortality. Early recognition of red flags, prompt imaging, withdrawal of offending drugs, and urgent biliary decompression when obstructed markedly improve outcomes.