Jaundice — Causes, Bilirubin, Liver Disease & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Jaundice (icterus) is a yellow discoloration of the skin, sclera (whites of the eyes), and mucous membranes caused by elevated serum bilirubin levels — typically above 35–50 µmol/L (2–3 mg/dL). It is not a disease itself but a clinical sign of an underlying disorder affecting bilirubin production, metabolism, or excretion. Jaundice is classified by mechanism: pre-hepatic (excess bilirubin production from haemolysis), hepatic (impaired liver uptake, conjugation, or excretion — from hepatitis, cirrhosis), and post-hepatic (biliary obstruction — gallstones, pancreatic cancer, bile duct strictures). Adult jaundice always requires investigation to identify the underlying cause. Jaundice (icterus) is the clinical manifestation of hyperbilirubinaemia — visible yellowing of the sclera (detected when serum bilirubin exceeds 35 mcmol/L) and skin (visible when bilirubin exceeds 50-85 mcmol/L). Bilirubin is produced from haemoglobin breakdown in the reticuloendothelial system — unconjugated (indirect) bilirubin, bound to albumin, is taken up by hepatocytes, conjugated with glucuronic acid, and excreted in bile into the intestines where bacteria convert it to urobilinogen (partly reabsorbed and excreted in urine; remainder converted to stercobilin giving faeces their brown colour). This precise pathway determines jaundice classification — abnormality at any step causes specific patterns of bilirubin elevation that differentiate pre-hepatic, hepatic, and post-hepatic causes. Adult jaundice always requires investigation — it is never a normal physiological finding except in neonates (physiological jaundice from immature hepatic bilirubin conjugation, peaking day 2-4). Jaundice is the presenting symptom of some of the most serious medical conditions — acute liver failure, cholangiocarcinoma, and pancreatic cancer — making timely clinical assessment and investigation critical.

Pre-hepatic (haemolytic) jaundice: increased red blood cell destruction from sickle cell disease, spherocytosis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, autoimmune haemolytic anaemia, and malaria. Hepatocellular (hepatic) jaundice: acute viral hepatitis (HAV, HBV, HEV), alcoholic hepatitis, autoimmune hepatitis, drug-induced liver injury (paracetamol, anti-TB drugs), non-alcoholic fatty liver disease, and cirrhosis. Cholestatic (post-hepatic/obstructive) jaundice: gallstones (choledocholithiasis), pancreatic cancer (most common cause of painless progressive jaundice in adults), bile duct cancer (cholangiocarcinoma), primary sclerosing cholangitis, and primary biliary cholangitis. Neonatal jaundice: physiological (universal, resolves by day 14), ABO/Rh incompatibility, G6PD deficiency, and biliary atresia. Pre-hepatic jaundice causes elevated unconjugated bilirubin from excessive haemolysis: sickle cell disease (intravascular haemolysis from rigid sickled erythrocytes — bilirubin pigment gallstones are a complication), spherocytosis (osmotic fragility testing diagnostic), G6PD deficiency (drug-triggered haemolysis — antimalarials, dapsone, nitrofurantoin, fava beans), autoimmune haemolytic anaemia (direct antiglobulin test/Coombs positive), and microangiopathic haemolytic anaemia (TTP, HUS, DIC, preeclampsia — HELLP syndrome). Hepatic jaundice causes: acute hepatitis A, B, E (vaccine-preventable); acute alcoholic hepatitis (elevated GGT, AST:ALT ratio above 2:1 — clinical diagnostic clue); paracetamol hepatotoxicity (most common cause of acute liver failure in the UK — dose-dependent with clear time-action relationship); drug-induced liver injury (DILI — over 1000 drugs implicated; most common drugs: antibiotics, anti-TB drugs, NSAIDs, herbal medicines, statin-induced cholestasis); Wilson's disease (copper accumulation causing acute liver failure with haemolysis and Coombs-negative Kayser-Fleischer rings — consider in any young patient with unexplained hepatitis). Post-hepatic: choledocholithiasis (gallstones in the common bile duct), pancreatic head carcinoma (painless progressive jaundice with Courvoisier's sign — palpable gallbladder — suggests malignant biliary obstruction), cholangiocarcinoma (hilar or distal bile duct tumour — Klatskin tumour most common).

Yellow discoloration of the sclera (earliest clinical sign — detected when bilirubin above 35 µmol/L) followed by skin yellowing and yellow mucous membranes. Accompanying features vary by cause: Dark urine (bilirubin excreted in urine in obstructive jaundice — tea-colored) and pale/clay-colored stools (absent bile in stool in biliary obstruction). Pruritus (severe itching from bile salt deposition in skin) in cholestatic jaundice. Fever, rigors, and right upper quadrant pain (Charcot's triad) indicate acute cholangitis — a medical emergency. Painless progressive jaundice with weight loss in an elderly patient strongly suggests pancreatic or bile duct cancer. Haemolytic jaundice causes mild yellow tinge without dark urine.

Liver function tests (LFTs): serum bilirubin (total, conjugated, unconjugated) characterizes the type of jaundice. Predominantly unconjugated (indirect) bilirubin indicates pre-hepatic cause; predominantly conjugated (direct) bilirubin indicates hepatic or post-hepatic cause. ALT and AST elevation indicates hepatocellular damage; elevated ALP and GGT indicate cholestasis. Viral hepatitis serology (HBsAg, anti-HCV, HAV IgM, HEV IgM) identifies infectious causes. Abdominal ultrasound is the first-line imaging for jaundice — identifies biliary dilatation, gallstones, liver parenchymal disease, and pancreatic masses. CT or MRCP (magnetic resonance cholangiopancreatography) further characterizes biliary anatomy. ERCP (endoscopic retrograde cholangiopancreatography) is both diagnostic and therapeutic for biliary stones. The bilirubin fractionation determines jaundice mechanism: predominantly unconjugated (indirect) hyperbilirubinaemia indicates pre-hepatic haemolysis or Gilbert's syndrome (a benign UGT1A1 promoter polymorphism affecting 5-10% of the population, causing mild intermittent jaundice with fasting or illness — entirely benign, requires no treatment). Predominantly conjugated (direct) hyperbilirubinaemia confirms hepatic or cholestatic jaundice. The hepatocellular versus cholestatic pattern: ALT and AST greater than 10x upper limit of normal with modest ALP elevation = hepatocellular; ALP and GGT greater than 3x with modest transaminases = cholestatic. Abdominal ultrasound assesses biliary duct dilatation (above 6 mm common bile duct = cholestasis/obstruction), gallstones, and liver parenchymal texture (cirrhosis, infiltration, tumour). MRCP (magnetic resonance cholangiopancreatography) provides non-invasive 3D biliary tree imaging without radiation — the first-choice investigation for suspected biliary obstruction following ultrasound. ERCP (endoscopic retrograde cholangiopancreatography) is both diagnostic and therapeutic — used for bile duct stone extraction, biliary stenting, and obtaining biliary brushings for malignancy cytology.

Treatment is directed entirely at the underlying cause of jaundice — there is no treatment for bilirubin accumulation independent of its cause. Haemolytic anaemia: treat the underlying haemolytic disorder (transfusion, corticosteroids for autoimmune haemolysis, splenectomy). Viral hepatitis A/E: supportive care; HBV: antiviral therapy (tenofovir, entecavir); HCV: direct-acting antiviral cure in 8–12 weeks. Alcoholic/drug-induced hepatitis: alcohol abstinence, stop offending drug, corticosteroids for severe alcoholic hepatitis. Biliary obstruction from gallstones: ERCP with sphincterotomy and stone extraction. Pancreatic or bile duct cancer: surgical resection (Whipple's procedure) if operable; biliary stenting (ERCP or percutaneous) for palliation. Neonatal jaundice: phototherapy (bili-lights); exchange transfusion for severe hyperbilirubinaemia. Haemolytic jaundice management: disease-specific treatment of the underlying haemolytic disorder; folic acid supplementation (5 mg daily) to support erythropoiesis in chronic haemolysis; transfusion for symptomatic anaemia. Acute alcoholic hepatitis with Maddrey DF above 32 or MELD above 21: prednisolone 40 mg/day for 28 days followed by Lille score assessment at 7 days — if score above 0.45 (non-response), prednisolone is discontinued. Paracetamol hepatotoxicity: N-acetylcysteine (NAC) by Rumack-Matthew protocol — 21-hour IV infusion (150 mg/kg in 200 mL 5% dextrose over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours) is the antidote, effective even up to 24 hours after ingestion in severe cases. Biliary obstruction from stones: ERCP with sphincterotomy and Dormia basket or balloon stone extraction achieves clearance in 90-95% of cases. Cholangitis: IV ceftriaxone 2 g daily (or piperacillin-tazobactam for severe cases) plus urgent ERCP biliary drainage within 24-48 hours (within 24 hours for severe/Reynold's pentad). Neonatal jaundice: phototherapy with blue-spectrum LED (430-490 nm wavelength); exchange transfusion for severe hyperbilirubinaemia above threshold curves.

Acute cholangitis from biliary obstruction with infection (bacteria ascending into bile ducts) causes Charcot's triad (fever, rigors, right upper quadrant pain) or Reynold's pentad (plus shock and confusion) — a life-threatening emergency requiring urgent ERCP biliary drainage and IV antibiotics. Acute liver failure from severe hepatocellular jaundice causes coagulopathy, hepatic encephalopathy, renal failure (hepatorenal syndrome), and death without liver transplantation. Kernicterus in neonates — bilirubin crosses the blood-brain barrier in severe neonatal hyperbilirubinemia, causing permanent neurological damage including cerebral palsy, deafness, and cognitive impairment — prevented by timely phototherapy or exchange transfusion.

Vaccinate against hepatitis A and hepatitis B — both vaccine-preventable causes of jaundice. Avoid excessive alcohol consumption — the most preventable cause of alcoholic hepatitis and cirrhosis. Check all medications (prescribed and over-the-counter) for hepatotoxic potential; never exceed recommended paracetamol dose (maximum 4 g/day, 2 g/day in liver disease). Gallstones can be prevented by maintaining healthy weight, avoiding rapid weight loss, and eating a low-fat, high-fiber diet. Neonatal jaundice: all newborns should be assessed for jaundice at 72 hours after birth; breastfeed early and frequently; check jaundice in premature infants at lower thresholds. Universal hepatitis B vaccination in infancy prevents the most common global cause of jaundice.

Any new jaundice (yellow eyes or skin) in an adult requires same-day or next-day medical assessment — jaundice is always significant and never normal in adults. Attend A&E immediately for: jaundice with fever, rigors, and right upper quadrant pain (Charcot's triad — bacterial cholangitis; potentially life-threatening requiring urgent biliary decompression); jaundice with confusion (possible hepatic encephalopathy); jaundice with severe abdominal pain; or jaundice with signs of liver failure (bruising, prolonged bleeding, leg swelling). For neonatal jaundice: all newborns with visible jaundice in the first 24 hours require same-day emergency assessment; jaundice persisting beyond 2 weeks in a term baby (3 weeks if premature) requires urgent GP assessment and serum bilirubin testing to exclude biliary atresia.