Cholestatic liver syndromes (PBC, PSC)

1. Cholestasis

• Stasis of bile — bile cannot flow from liver to duodenum.
• Hallmarks: ↑ alkaline phosphatase, pruritus (→ later jaundice), bile in canaliculi / hepatocytes.

2. Primary Biliary Cholangitis (PBC)

• Formerly “primary biliary cirrhosis”.
• Chronic, progressive, autoimmune cholestatic liver disease; often fatal.
• Middle-aged women; peak 40–50 yr.

Morphology

• Destruction of small–medium intrahepatic bile ducts with granuloma formation → cholestasis → cirrhosis / liver failure.

Pathogenesis & clinical course

• Anti-mitochondrial antibodies (AMA) at high titer — hallmark (target unknown).
• Insidious onset: pruritus → later jaundice (cholestasis ≠ jaundice; it causes it).
• Over ~2 decades: hepatic decompensation → portal hypertension, variceal bleeding, encephalopathy.
• Labs: ↑ alkaline phosphatase + ↑ cholesterol; hyperbilirubinemia late.
• Extrahepatic associations: sicca complex (Sjögren syndrome), scleroderma.

3. Secondary Biliary Cholangitis / Cirrhosis

• Consequence of chronic biliary obstruction — usually gallstones or benign tumors.
• Should not develop in developed countries (cholestasis + jaundice are recognizable and surgically relievable).

4. Primary Sclerosing Cholangitis (PSC)

• Believed autoimmune; more common in males, ~20 yr.
• Progressive fibrosis + destruction of intra- AND extrahepatic bile ducts.
• Concentric (“onion-skin”) sclerosis around ducts → segmental beading.
• Strong association with IBD, especially ulcerative colitis; ANCA-positive → immunologically mediated.
• Sx: progressive fatigue, pruritus, jaundice.
• Late: weight loss, ascites, variceal bleeding, encephalopathy, cholangiocarcinoma risk.
• Poor prognosis → liver transplantation.

5. PBC vs PSC at a Glance

Feature	PBC	PSC
Sex / age	Female, 40–50 yr	Male, ~20 yr
Ducts affected	Small–medium intrahepatic only	Intra + extrahepatic (segmental)
Histology	Granulomas, lymphocytic destruction	Concentric “onion-skin” periductal fibrosis
Serology	AMA (anti-mitochondrial Ab)	ANCA
Associated dz	Sjögren, scleroderma	Ulcerative colitis (IBD)
Cancer risk	HCC (post-cirrhosis)	Cholangiocarcinoma
End-stage Tx	Transplant	Transplant

💡 High-yield: PBC = middle-aged ♀, AMA+, small intrahepatic ducts + granulomas, +Sjögren / scleroderma. PSC = young ♂, ANCA+, intra and extrahepatic onion-skin fibrosis, strongly linked to ulcerative colitis, ↑ cholangiocarcinoma. Both: pruritus precedes jaundice, ↑ ALP, end-stage → transplant.