Primary sclerosing cholangitis

Chronic inflammatory disease characterised by strictures of the intrahepatic and extrahepatic biliary tree

• Generally progressive

Pathophysiology

• Poorly understood
• Likely autoimmune
• ?Bacterial translocation and infection
• Genetic factors, although complex and polygenetic, exist

Aetiology

• 2/3 male
• Average age 40s

Associated with:

• • UC (most common - 60-90% of cases)
  • Crohns
  • T1DM
  • Thyroiditis
  • Autoimmune hepatitis
  • Ankylosing spondylitis
  • Coeliac disease
  • Acute pancreatitis
  • Pancreatic adenocarcinoma
  • Gallstones
  • GB polyps/cancer
    • Some recommend annual biliary USS
    • Cholecystectomy for ANY size polyp
  • Colorectal adenocarcinoma - need frequent surveillance
  • Cholangiocarcinoma (as high as 15%)
    • Not associated with duration of PSC disease or presence of cirrhosis
    • No high-risk group has been identified to target with screening protocols
    • Screening consists of serial MRCP and CA 19-9 (can be falsely elevated in setting of jaundice though)
    • ERCP for those with increasing CA 19-9 or those in whom dominant strictures develop or progress
    • Need complete resection to manage
  • HCC

Distribution

• Intra and extrahepatic 75%
• Only intrahepatic 15%
• Only extrahepatic 10%
• 'Dominant stricture' = a narrowing 1.5mm or less in CBD or 1mm or less in CHD

Presentation

• Non-specific
• Often asymptomatic
• Often recurrent cholangitis leading to secondary biliary cirrhosis and not uncommonly, biliary malignancy
• Can lead to end-stage liver disease/portal HTN
• Present intra and extra hepatic ducts in 70%, just intra-hepatic in 25% and just extra-hepatic in <5%
• Can be classic biliary - RUQ pain, pruritis, fatigue
• Can be deranged LFTs/liver failure, especially if intrahepatic disease primarily

Diagnosis

• MRCP is gold standard
• ERCP

Workup

• Need liver biopsy to document degree of fibrosis
• Colonoscopy (exclude CRC and diagnose IBD)

Medical therapy

• No drug has slowed disease progression, prolonged survival or improved outcomes in patients with PSC
• Future therapies?
  • Antifibrotic agents
  • TNF-a inhibitors
  • T-cell modulators
  • Inhibitors of 'toxic bile' formation (Farnesoid X agonists)

Endoscopic/IR therapies

• ERCP best treatment methodology
• Opportunity for cholangioscopy/EUS - better chance of identifying CCA
• Balloon dilation - 80% get a good clinical response
• If no response: endobiliary stents
  • Need to remove after 6-8 weeks
  • Complications - bleeding, perforation, pancreatitis, cholangitis
• The role of PTC is mostly limited to those with previous RYGB or other biliary bypass

Surgical resection

• Should generally be avoided in PSC - limited impact on survival, significant morbidity, increased scarring in porta hepatis which may complicate future transplant
• Only exception would be patients with early disease, but a dominant extrahepatic stricture, who may be eligible for biliary reconstruction (hepaticojejunostomy)

Liver transplant

• Use Mayo Model to predict optimal timing of transplant
  • Bilirubin
  • Degree of fibrosis
  • Presence of splenomegaly
  • Age
• Recurrent PSC in 25% (IBD and intact colon puts them at risk)
• If unsuspecting small CCA (<1cm) is found at explant, the long-term prognosis seems to be unaffected

Complications

• CCA (lifetime risk 10-20%) - annual MRCP and CA19-9 is a sensible screening pattern)
• Cholelithiasis/GB CA
• Cholestasis-associated problems
  • Metabolic bone disease
  • Fat-soluble vitamin deficiencies
  • Choledocholithiasis
• Higher risk of CRC

Prognosis

• Average survival from diagnosis to death/transplantation is 12-18 years