What is the primary approach to treating Primary Sclerosing Cholangitis (PSC)?

Primary Approach to Treating Primary Sclerosing Cholangitis

There is no effective medical therapy that halts disease progression or improves survival in PSC; management focuses on symptom control, complication management, and liver transplantation for end-stage disease. 1

Medical Therapy: Limited Role

Ursodeoxycholic acid (UDCA) is not recommended for routine treatment of PSC, as randomized controlled trials have not demonstrated improvement in survival or disease progression. 1, 2 This represents a critical departure from other cholestatic liver diseases where UDCA has proven benefit.

• Corticosteroids and immunosuppressants are not indicated for classic PSC 1
• These agents should only be considered in patients with overlap syndrome (PSC plus autoimmune hepatitis features) or IgG4-related sclerosing cholangitis 1

Symptom Management

Pruritus

• First-line: Cholestyramine (or similar bile acid sequestrants) 3, 1
• Second-line: Rifampicin or naltrexone 3, 1
• Always evaluate for and treat dominant strictures, as biliary obstruction can worsen pruritus 3

Nutritional Support

• Fat-soluble vitamin deficiency is common in advanced PSC; maintain a low threshold for empirical replacement 3, 1
• Screen for and treat osteoporosis according to national guidelines 3, 1

Management of Dominant Strictures

Endoscopic therapy is the cornerstone of managing symptomatic dominant strictures (defined as stenosis ≤1.5 mm in common bile duct or ≤1 mm in hepatic duct). 3

Indications for Intervention

Patients with dominant strictures presenting with: 3

• Cholangitis
• Jaundice
• Worsening pruritus
• Right upper quadrant pain
• Deteriorating biochemical indices

Endoscopic Approach

• Balloon dilatation is preferred over stent placement, as stenting is associated with increased complications 3, 1
• Stents should be reserved only for strictures refractory to dilatation 3
• Mandatory: Obtain brush cytology and/or endoscopic biopsy before any therapeutic intervention to exclude cholangiocarcinoma 3
• Administer perioperative antibiotics, as contrast injection into obstructed ducts can precipitate cholangitis 3

Alternative Approaches

• Percutaneous transhepatic cholangiography is reserved for proximal dominant strictures when endoscopic approach fails, though it carries higher morbidity 3
• Surgical biliary bypass (extrahepatic bile duct resection with Roux-en-Y hepaticojejunostomy) may be considered in highly selected non-cirrhotic patients refractory to endoscopic/percutaneous management 3

Important caveat: Retrospective data suggest endoscopic therapy may improve survival compared to predicted Mayo Risk Score (5-year survival 83% vs 65% predicted), though no randomized controlled trials exist. 3

Bacterial Cholangitis Management

• Acute cholangitis: Antimicrobial therapy combined with correction of bile duct obstruction 3
• Recurrent cholangitis: Prophylactic long-term antibiotics 3
• Refractory bacterial cholangitis is an indication for liver transplantation evaluation 3

Surveillance for Complications

Cholangiocarcinoma

• Occurs in 10-15% of PSC patients, often presenting as dominant strictures 3
• CA19-9 has low diagnostic accuracy and is not recommended for routine surveillance 3
• When suspected, refer for specialist multidisciplinary team review with contrast-enhanced cross-sectional imaging 3

Colorectal Cancer

• Annual colonoscopic surveillance is mandatory from diagnosis in PSC patients with coexistent inflammatory bowel disease 3, 1
• Patients without IBD may benefit from colonoscopy every 5 years 3, 1

Gallbladder Polyps

• Annual ultrasound surveillance of the gallbladder 3, 1
• Management of identified polyps should be directed by specialist hepatopancreaticobiliary multidisciplinary team 3

Liver Transplantation

Liver transplantation is the only life-extending therapy for PSC and should be considered in eligible patients with end-stage disease. 3, 1

• Excellent outcomes: 85% survival at 5 years, 70% at 10 years 3
• Ultimately required in approximately 40% of PSC patients 4
• Assess eligibility according to national guidelines 3, 1
• Critical timing consideration: Refractory bacterial cholangitis alone can be an indication for transplantation 3

Ongoing Monitoring

• Lifelong follow-up is essential given the unpredictable disease course and severe complications 1
• Risk stratification using non-invasive assessment tools 1
• Patients with symptomatic, evolving, or complex disease require expert multidisciplinary assessment 3