What is the management approach for Primary Sclerosing Cholangitis (PSC)?

Management of Primary Sclerosing Cholangitis

There is no effective medical therapy for PSC outside of liver transplantation; management focuses on lifelong surveillance for complications, endoscopic treatment of dominant strictures, and timely referral for transplantation. 1, 2

Medical Therapy: What NOT to Do

Do not use ursodeoxycholic acid (UDCA) for routine treatment of PSC. 1, 2 While older 2010 guidelines were equivocal about UDCA, the most recent 2019 British Society of Gastroenterology guidelines provide a STRONG recommendation against its use based on MODERATE to HIGH quality evidence. 1 UDCA at standard doses (13-15 mg/kg/day) improves liver biochemistry but does not prevent treatment failure, death, or transplantation. 1 High-dose UDCA has actually been shown to have negative effects in advanced disease. 3

Do not use corticosteroids or immunosuppressants for classic PSC. 1, 2 These agents are not indicated unless the patient has:

• PSC-autoimmune hepatitis overlap syndrome 1, 2
• IgG4-related sclerosing cholangitis 1, 2

Diagnostic Approach

Use MRCP as the principal imaging modality for suspected PSC. 1, 2 MRCP is more than 80% sensitive and more than 90% specific for PSC diagnosis. 4

Reserve ERCP exclusively for: 1, 2

• Tissue acquisition (cytological brushings) from strictures
• Therapeutic intervention for dominant strictures
• Evaluation when cholangiocarcinoma is suspected

Perform liver biopsy only for: 1

• Suspected small duct PSC
• Possible overlap syndromes (PSC-AIH)
• Unclear diagnosis

Surveillance Strategy: Lifelong Monitoring Required

All PSC patients require lifelong follow-up given the unpredictable disease course and serious complications. 1, 2

Cholangiocarcinoma Surveillance

Perform annual contrast-enhanced MRI to screen for cholangiocarcinoma. 2 The cumulative lifetime risk of cholangiocarcinoma is 10-20%, and it accounts for a large proportion of PSC mortality. 5 When clinical suspicion is high (deteriorating constitutional status or liver biochemistry), repeat CA 19-9 and cholangiography with brushings for cytology including FISH studies. 1

Inflammatory Bowel Disease Surveillance

Screen all PSC patients for colitis with colonoscopy and colonic biopsies. 1, 2 Up to 80% of PSC patients have concomitant IBD, predominantly ulcerative colitis. 2

For PSC patients with IBD: 1

• Annual colonoscopic surveillance from diagnosis of colitis (colorectal cancer risk is substantially elevated)
• For those without IBD: colonoscopy every 5 years or sooner if new symptoms develop

Additional Surveillance

Perform annual gallbladder ultrasound. 6 Gallbladder polyps and adenocarcinoma are recognized complications. 5

Screen for osteoporosis with risk assessment. 2, 7, 6 Once detected, treat according to national guidelines. 6

Screen for esophageal varices when cirrhosis or portal hypertension is present, following standard cirrhosis guidelines. 1, 2

Management of Complications

Dominant Strictures

Treat dominant strictures with endoscopic balloon dilatation, preferably without stenting. 2, 6 This approach improves liver biochemistry and pruritus. 2

Mandatory pathological sampling of suspicious strictures during ERCP to exclude cholangiocarcinoma. 6 Patients should undergo expert multidisciplinary evaluation before ERCP is performed. 6

Bacterial Cholangitis

Treat with antimicrobial therapy and bile duct decompression. 2

Pruritus

First-line: cholestyramine (or similar bile acid sequestrant). 6

Second-line: rifampicin or naltrexone. 6

Nutritional Deficiencies

Maintain low threshold for empiric replacement of fat-soluble vitamins in advanced PSC. 6 Malnutrition and vitamin deficiencies are relatively common. 6

Portal Hypertension

Manage according to standard cirrhosis guidelines. 2

Liver Transplantation

Liver transplantation is the only curative therapy for advanced PSC. 2, 7 Approximately 40% of patients ultimately require transplantation. 5

Assess eligibility and refer according to national guidelines when: 7, 6

• Bilirubin levels indicate advanced liver disease
• Evidence of decompensated liver disease develops
• Estimated 10-year survival is approximately 65%, but individual variation is substantial 1

For early-stage cholangiocarcinoma not amenable to surgical resection, consider liver transplantation following neoadjuvant therapy at experienced transplant centers. 1 PSC has excellent transplant outcomes compared to other indications, though disease recurrence can occur. 5

Prognostic Assessment

Do not rely on prognostic models to predict outcomes in individual patients. 1 While models incorporating age, bilirubin, AST, albumin, and variceal bleeding history exist, no consensus exists regarding the optimal model, and their ability to predict individual patient outcomes is limited. 1

Use non-invasive risk stratification, but recognize that no single method can be recommended at present. 1

Special Considerations

Pregnancy in cirrhotic PSC patients carries increased maternal and fetal risks; provide preconception counseling and specialized monitoring. 6

Encourage participation in patient support groups. 6