Primary Sclerosing Cholangitis

Primary sclerosing cholangitis is a chronic fibroinflammatory cholangiopathy causing progressive multifocal stricturing of intrahepatic and extrahepatic bile ducts.

It is strongly associated with inflammatory bowel disease, particularly ulcerative colitis.

Progressive disease can cause recurrent bacterial cholangitis, biliary cirrhosis and portal hypertension.

PSC substantially increases the risk of cholangiocarcinoma, gallbladder malignancy and, when associated with inflammatory bowel disease, colorectal cancer.

No medical therapy reliably reverses established PSC or prevents progression in all patients. Liver transplantation is the definitive treatment for advanced disease.

Many patients are initially identified through cholestatic liver abnormalities.

Symptomatic disease can cause:

• Fatigue
• Pruritus
• Right upper quadrant discomfort
• Jaundice
• Recurrent fever from bacterial cholangitis

Rapid worsening of jaundice, new weight loss or a new focal biliary obstruction should raise concern for cholangiocarcinoma rather than being attributed automatically to progression of benign PSC.

MRCP: diagnostic imaging of choice; demonstrates multifocal biliary stricturing with intervening normal or dilated segments.

Do not use ERCP simply to establish the diagnosis because it adds pancreatitis and cholangitis risk.

Liver biopsy is mainly required when MRCP is normal but small duct PSC is suspected, or when autoimmune hepatitis overlap is possible.

At diagnosis, evaluate for inflammatory bowel disease with colonoscopy and biopsies.

Medical management

There is no proven curative drug treatment.

In a patient with persistently elevated alkaline phosphatase or significant cholestatic symptoms, a monitored trial of:

Ursodeoxycholic acid 13 to 23 mg/kg/day orally in divided doses

can be considered.

Continue only if there is meaningful biochemical or symptomatic improvement over approximately 12 months. Avoid very high dose ursodeoxycholic acid because doses around 28 to 30 mg/kg/day have been associated with worse clinical outcomes.

For troublesome pruritus:

Cholestyramine 4 g orally once daily, increasing according to response up to a total of approximately 4 to 16 g/day.

Other medications should be taken at least 1 hour before or 4 to 6 hours after cholestyramine because it interferes with absorption.

Relevant biliary stricture

New obstructive jaundice, bacterial cholangitis or significant deterioration in cholestatic liver tests should trigger MRCP.

A clinically relevant high grade stricture requires ERCP with brush cytology, fluorescence in situ hybridisation where available, and intraductal biopsy, because cholangiocarcinoma must be excluded.

Balloon dilate a symptomatic stricture when drainage can be improved.

If a plastic biliary stent is necessary, remove it within approximately 4 weeks rather than leaving it indefinitely because stent occlusion can precipitate cholangitis.

Acute bacterial cholangitis requires IV antibiotics and urgent biliary decompression when obstruction persists.

Cancer surveillance

For adult large duct disease, perform annual MRI with MRCP, with or without CA 19 9, for cholangiocarcinoma and gallbladder malignancy surveillance.

A gallbladder polyp above approximately 8 mm should prompt consideration of cholecystectomy because malignancy risk is substantial.

PSC with inflammatory bowel disease requires high intensity colonoscopic surveillance, generally every 1 to 2 years.

Transplantation

Consider liver transplantation for:

• Decompensated cirrhosis
• Recurrent bacterial cholangitis despite adequate biliary management
• Refractory severe pruritus
• Persistent severe jaundice
• High grade biliary dysplasia
• Progressive portal hypertension or liver failure.