Primary Sclerosing Cholangitis

Also known as: PSC

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.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Obstructive Jaundice

Obstructive jaundice is conjugated hyperbilirubinaemia caused by impaired drainage of bile from the liver into the duodenum.

The obstruction may be intrahepatic or extrahepatic, benign or malignant.

Important surgical causes include:

Choledocholithiasis
Acute cholangitis
Benign biliary stricture
Mirizzi syndrome
Pancreatic head cancer
Cholangiocarcinoma
Ampullary tumour
Gallbladder cancer

Management requires identification of the level, cause and urgency of obstruction before drainage is performed.

Laboratory testing usually demonstrates predominantly conjugated hyperbilirubinaemia with a cholestatic rise in alkaline phosphatase and gamma glutamyl transferase.

Right upper quadrant ultrasound: first investigation; determine whether the biliary tree is dilated and identify the approximate level of obstruction.

MRCP: define biliary anatomy and the obstruction noninvasively.

Contrast CT: particularly important when pancreatic or biliary malignancy is suspected.

Endoscopic ultrasound is useful for distal common bile duct, ampullary and pancreatic lesions and permits tissue acquisition.

ERCP should principally be used when therapy is expected, rather than as a routine diagnostic investigation.

Treat the cause rather than the bilirubin value alone.

Cholangitis

Infection plus obstruction requires urgent antibiotics and biliary decompression.

ERCP is preferred when the obstruction is endoscopically accessible.

Choledocholithiasis

Perform ERCP with sphincterotomy and stone extraction, or operative common bile duct exploration depending on local expertise.

Follow gallbladder derived duct stones with definitive cholecystectomy.

Malignant obstruction

Do not automatically place a biliary stent before potentially curative surgery.

Preoperative drainage is appropriate when there is:

Acute cholangitis
Severe symptomatic jaundice with significant organ dysfunction
Renal impairment attributable to obstruction
Planned neoadjuvant treatment
Significant delay before surgery
Need to optimise a future liver remnant before major hepatectomy

For unresectable malignant obstruction causing jaundice, pruritus, cholangitis or liver dysfunction, internal endoscopic drainage is generally preferred when technically feasible. Percutaneous drainage is used when endoscopic access fails or the anatomy makes it more effective.

Coagulopathy

Check INR in prolonged cholestasis or before invasive procedures.

When vitamin K deficiency is suspected:

Vitamin K 10 mg IV slowly or orally once, then reassess coagulation according to urgency and clinical response.

Failure of INR to correct should prompt consideration of significant hepatic synthetic dysfunction rather than simply escalating vitamin K.

Do not delay urgent biliary drainage in septic cholangitis merely to normalise bilirubin. The immediate objective is decompression of the infected obstructed system.

Primary Sclerosing Cholangitis

Overview

Clinical Features

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management