Key Facts

PSC is a chronic progressive cholangiopathy characterised by inflammation and fibrosis of the bile ducts leading to strictures, cholestasis, and ultimately biliary cirrhosis. Its strong association with IBD and risk of cholangiocarcinoma make it a complex condition to manage.

Epidemiology

Prevalence ~6 per 100,000 in the UK. Incidence ~1 per 100,000 per year. Male predominance (2:1). Mean age at diagnosis 30-40 years. Higher prevalence in Northern European populations. ~70% of PSC patients have IBD (usually UC).

Aetiology

Unknown — likely autoimmune with genetic susceptibility (HLA-B8, DR3, DR2) and environmental triggers. The gut-liver axis is important: aberrant homing of gut-primed T cells to the liver via the portal circulation may drive biliary inflammation. The association with IBD supports this "leaky gut" hypothesis.

Pathophysiology

Chronic inflammation of bile duct epithelium (cholangiocytes) → concentric periductal fibrosis ("onion-skinning") → stricture formation → bile stasis → secondary biliary cirrhosis. Both large (intra- and extrahepatic) and small duct forms exist. The resulting cholestasis causes pruritus, malabsorption, and progressive liver failure. Chronic inflammation and bile stasis predispose to cholangiocarcinoma.

Early Disease

• Often asymptomatic (detected incidentally on LFTs)
• Fatigue
• Pruritus (may be severe)
• RUQ discomfort

Progressive Disease

• Jaundice (fluctuating — may relate to dominant strictures)
• Recurrent cholangitis (fever, rigors, jaundice — bacterial superinfection of stagnant bile)
• Hepatomegaly, splenomegaly
• Features of cirrhosis/portal hypertension

Associated Conditions

• IBD (~70%) — usually UC (mild pancolitis; often subclinical)
• Increased colorectal cancer risk in PSC-IBD (5× risk compared to UC alone)
• Autoimmune hepatitis overlap (~10%)
• Gallbladder polyps/cholangiocarcinoma

Red Flags

• Rapidly progressive jaundice (cholangiocarcinoma)
• Dominant stricture on MRCP (cholangiocarcinoma risk)
• Weight loss in established PSC (malignancy)
• Recurrent cholangitis episodes

Bloods

• ALP/GGT: raised (cholestatic pattern) — hallmark
• Bilirubin: normal early; rising indicates advanced disease or dominant stricture
• IgG: may be mildly raised (overlap with AIH if significantly raised)
• pANCA: positive in ~60% (atypical — perinuclear)
• AMA: negative (distinguishes from PBC)
• CA19-9: may be raised (but poor specificity — also raised in cholangitis/cholestasis without malignancy)
• IgG4: exclude IgG4-related disease

Imaging

• MRCP: diagnostic — multifocal strictures and dilatations of intra- and/or extrahepatic bile ducts ("beaded" or "pruned tree" appearance)
• USS abdomen: liver assessment, gallbladder polyps (annual screening)
• FibroScan: fibrosis assessment (may be confounded by cholestasis)

Special Tests

• Liver biopsy: NOT required for diagnosis if MRCP characteristic; indicated for: suspected small-duct PSC (normal MRCP), overlap syndrome, staging
  • Histology: concentric periductal fibrosis ("onion-skinning"), bile duct loss, periportal fibrosis
• Colonoscopy: ALL PSC patients should have colonoscopy at diagnosis to screen for IBD; annual surveillance colonoscopy if PSC-IBD (high CRC risk)
• ERCP + brush cytology: for dominant stricture assessment (cholangiocarcinoma diagnosis)
• FISH (fluorescence in situ hybridisation): on biliary brushings for cholangiocarcinoma detection

Non-pharmacological

• Annual colonoscopy surveillance: ALL PSC-IBD patients (5× CRC risk)
• Annual USS + CA19-9: cholangiocarcinoma and gallbladder screening
• MRCP: if dominant stricture or worsening LFTs
• Bone health: DEXA, calcium/vitamin D
• Fat-soluble vitamin supplementation: if cholestasis advanced

Pharmacological

• UDCA: widely used (13-15 mg/kg/day) but evidence for benefit in PSC is LIMITED — may improve LFTs but NOT proven to slow disease progression or improve transplant-free survival. High-dose UDCA (28-30 mg/kg/day) may be HARMFUL (Lindor et al., Hepatology 2009)
• Vancomycin: emerging evidence, particularly in paediatric PSC; adult trials ongoing
• Pruritus: cholestyramine, rifampicin, naltrexone (same approach as PBC)
• Recurrent cholangitis: intermittent antibiotics (ciprofloxacin, co-amoxiclav); prophylactic antibiotics if very frequent
• IBD management: standard UC/Crohn's therapy; note that colectomy does NOT improve PSC course

Surgical/Interventional

• ERCP: for dominant stricture dilatation ± short-term stenting; improves jaundice and cholangitis; brush cytology for cholangiocarcinoma screening
• Liver transplantation: only curative option; indicated for decompensated disease, recurrent cholangitis, intractable pruritus, or cholangiocarcinoma within criteria; 5-year survival ~80%; PSC recurs in ~20-25% of grafts
• Cholecystectomy: if gallbladder polyps >8 mm (high cholangiocarcinoma risk)

Referral Criteria

• All PSC to hepatology for specialist management
• Colonoscopy for IBD screening at diagnosis
• Transplant assessment if decompensated or cholangiocarcinoma
• HPB surgery for suspicious strictures/gallbladder lesions

Median transplant-free survival from diagnosis is ~12-15 years. Disease course is highly variable. Cholangiocarcinoma develops in 10-15% (lifetime risk) — leading cause of death in PSC; often diagnosed late. CRC risk in PSC-IBD is 5× that of UC alone — annual colonoscopy surveillance is essential. Post-transplant 5-year survival ~80%; PSC recurrence in graft ~20-25%.

PSC Surveillance Schedule

PSC vs IgG4-Sclerosing Cholangitis