Congenital Liver Diseases

Biliary Atresia - Bile Duct Blockade

Progressive fibro-obliteration of extrahepatic biliary tree causing bile flow obstruction. Commonest cause of surgical neonatal jaundice.

• Types (Kasai):
  • Type I: Common bile duct.
  • Type II: Common hepatic duct.
  • Type III: Porta hepatis (most common, ~90%).
• Clinical: Jaundice (>2 wks), acholic stools, dark urine, hepatomegaly.
• Diagnosis:
  • ↑ Direct bilirubin, ↑ GGT.
  • Ultrasound: Triangular cord sign.

    ⭐ Triangular cord sign on US is highly suggestive.

  • HIDA scan: No bowel excretion.
  • Liver biopsy: Ductular proliferation, fibrosis.
  • Intraoperative cholangiogram (gold standard).
• Management:
  • Kasai portoenterostomy (ideal <60-90 days).
  • Liver transplant (failed Kasai/late).
• Complications: Cholangitis, portal HTN, cirrhosis.

Neonatal Cholestasis & Hepatitis - When Yellow Spells Trouble

• Definition: Jaundice >14 days + conjugated hyperbilirubinemia (CB >1 mg/dL or >20% of Total Bilirubin).
• Etiology:
  • Obstructive: Biliary Atresia (BA), choledochal cyst.
  • Intrahepatic:
    • Idiopathic Neonatal Hepatitis (INH): Commonest; giant cells on biopsy.
    • Infections (TORCH), Metabolic (A1AT def.).
• Clinical: Jaundice, dark urine, acholic stools, hepatomegaly.
• Investigations: LFTs (↑CB, ↑GGT), USG, HIDA, Liver Biopsy.

  ⭐ GGT markedly ↑ in Biliary Atresia (>300 IU/L), helps differentiate from Neonatal Hepatitis.

• Management: Treat cause. Supportive: MCT oil, Vitamins A,D,E,K, UDCA.

Metabolic Liver Diseases - Enzyme Errors Wreak Havoc

• Inherited enzyme defects disrupting liver metabolism, leading to organ damage.
• Wilson's Disease: ATP7B gene defect → ↓copper (Cu) excretion. Kayser-Fleischer rings, ↑urinary Cu. Tx: Chelators (e.g., Penicillamine, Trientine).
• Hereditary Hemochromatosis: HFE gene defect → ↑iron (Fe) absorption. "Bronze diabetes", cirrhosis, cardiomyopathy. ↑Ferritin, ↑transferrin saturation. Tx: Phlebotomy.
• Alpha-1 Antitrypsin (A1AT) Deficiency: SERPINA1 gene defect → misfolded A1AT protein accumulates in hepatocytes (PAS+ globules, diastase-resistant). Results in cirrhosis & emphysema.
• Galactosemia: Galactose-1-Phosphate Uridyltransferase (GALT) enzyme deficiency → galactose-1-phosphate accumulation. Jaundice, hepatomegaly, cataracts, E. coli sepsis in neonates. Tx: Lactose/galactose-free diet.

⭐ Alpha-1 Antitrypsin deficiency characteristically shows PAS-positive, diastase-resistant globules, typically found in periportal hepatocytes.

Syndromic & Structural Conditions - When Liver's Not Alone

• Alagille Syndrome (ALGS): AD; JAG1/NOTCH2. Paucity of intrahepatic bile ducts.
  • Key: Cardiac (pulm. stenosis), skeletal (butterfly vertebrae), ocular (post. embryotoxon), characteristic facies. 📌 5 major criteria (cardiac, skeletal, ocular, facial, liver).

  ⭐ Liver biopsy: paucity of interlobular bile ducts (<0.5 bile ducts/portal tract).

• Caroli Disease: AR; PKHD1. Saccular intrahepatic bile duct dilatation.
  • "Central dot sign" (portal vein in dilated duct) on imaging.
  • Risks: cholangitis, stones, cholangiocarcinoma.
• Caroli Syndrome: Caroli disease + Congenital Hepatic Fibrosis (CHF) → portal HTN.
• Congenital Hepatic Fibrosis (CHF): AR; PKHD1. Portal fibrosis, abnormal portal veins.
  • Portal HTN (varices), preserved LFTs initially. Assoc. ARPKD.
• Biliary Atresia Splenic Malformation (BASM): Biliary atresia + splenic/laterality defects (e.g., asplenia, situs inversus).

High‑Yield Points - ⚡ Biggest Takeaways

• Gilbert's syndrome: Mild unconjugated hyperbilirubinemia due to UGT1A1 mutation.
• Crigler-Najjar Type I: Severe unconjugated hyperbilirubinemia, absent UGT, kernicterus. Type II responds to phenobarbital.
• Dubin-Johnson syndrome: Conjugated hyperbilirubinemia, black liver, defective MRP2.
• Rotor syndrome: Conjugated hyperbilirubinemia, no liver pigmentation, defective OATP1B1/3.
• Alagille syndrome: Paucity of bile ducts, butterfly vertebrae, pulmonary stenosis.
• Biliary atresia: Neonatal cholestasis, acholic stools, Kasai procedure needed.
• Congenital hepatic fibrosis: Linked to ARPKD, causes portal hypertension.