Primary Sclerosing Cholangitis (PSC)

Risk factors

• Male sex
• Inflammatory bowel disease (particularly pancolitis with rectal sparing)
• Family history of PSC or autoimmune disease
• Smoking is protective (in contrast to most autoimmune diseases)

Pathophysiology

Multifactorial autoimmune pathogenesis with T-cell-mediated injury to biliary epithelium in a genetically susceptible host. Resulting concentric 'onion-skin' periductal fibrosis obliterates small ducts and produces multifocal strictures and dilations of medium and large ducts. Progression to biliary cirrhosis, portal hypertension, and end-stage liver disease occurs over years to decades.

Clinical presentation

Differential diagnosis

• Primary biliary cholangitis — Female predominance, intrahepatic small-duct disease, AMA positive, normal MRCP
• Secondary sclerosing cholangitis — Cause identified — recurrent cholangitis, biliary surgery, ischemic, AIDS cholangiopathy, ICU-related, drug-induced
• IgG4-related sclerosing cholangitis — Elevated IgG4, mass-like infiltrates, responsive to corticosteroids
• Cholangiocarcinoma — Mass, dominant stricture; can complicate established PSC — high risk and difficult to distinguish
• AIDS cholangiopathy — Cryptosporidium, CMV in immunocompromised; papillary stenosis with intrahepatic strictures
• Choledocholithiasis with cholangitis — Acute Charcot triad, dilated CBD with stones on imaging

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Cholestatic LFTs<br/>± known IBD] --> B[MRCP]
  B --> C{Multifocal strictures<br/>+ dilations beaded?}
  C -->|Yes| D[Likely PSC<br/>Exclude IgG4-SC, secondary causes]
  C -->|No, LFTs persist| E[Liver biopsy<br/>r/o small-duct PSC]
  D --> F[Colonoscopy at dx<br/>annual if IBD present]
  D --> G[Annual MRI/MRCP + CA 19-9<br/>cholangiocarcinoma surveillance]
  D --> H[Annual gallbladder US<br/>any polyp ≥8 mm chole]
  D --> I{Symptomatic dominant<br/>stricture or cholangitis?}
  I -->|Yes| J[ERCP: balloon dilation,<br/>brushings, short-term stent if needed]
  I -->|No| K[Symptom control<br/>± consider UDCA case-by-case]
  D --> L[Liver transplant for ESLD,<br/>refractory cholangitis, intractable pruritus]

Treatment

Complications

• Cholangiocarcinoma (~10-15% lifetime risk; difficult to detect early)
• Gallbladder carcinoma (markedly elevated risk)
• Colorectal cancer in PSC-IBD (greater risk than IBD alone)
• Hepatocellular carcinoma in cirrhotic PSC
• Recurrent bacterial cholangitis
• Dominant strictures (10-50%) with cholestasis and infection risk
• Biliary cirrhosis with portal hypertension, varices, ascites
• Metabolic bone disease, fat-soluble vitamin deficiencies
• Recurrence in transplanted graft (~20-25%)

PANCE pearls

• Young to middle-aged man with UC and elevated alkaline phosphatase — MRCP for PSC.
• Beaded appearance with alternating strictures and dilations on MRCP is the hallmark.
• Always colonoscope at PSC diagnosis — many have undiagnosed IBD; annual surveillance thereafter due to elevated colorectal cancer risk.
• Avoid high-dose UDCA (≥28-30 mg/kg/day) — increases adverse outcomes (Lindor 2009 trial).
• A new dominant stricture, sudden worsening of cholestasis, weight loss, or rising CA 19-9 in PSC must trigger urgent imaging and ERCP with brushings for cholangiocarcinoma.

References

• AASLD 2010/2023 — AASLD Practice Guideline: Diagnosis and Management of Primary Sclerosing Cholangitis (Chapman et al., Hepatology 2010; 2023 update Bowlus et al.)
• EASL 2022 — EASL Clinical Practice Guidelines on sclerosing cholangitis (J Hepatol 2022)
• ACG 2023 — ACG Clinical Guideline: Primary Sclerosing Cholangitis and Primary Biliary Cholangitis (Bowlus et al., 2023)