Primary Sclerosing Cholangitis (PSC)

Overview of PSC

Primary sclerosing cholangitis is a life-threatening idiopathic chronic cholestatic disease affecting the intra- and/or extrahepatic bile ducts of the liver and which cannot be ascribed to another cause, thus differentiating it from secondary sclerosing cholangitis. Inflammation and fibrosis of the bile ducts leading to formation of a beaded pattern and multifocal bile duct strictures are the hallmark of this progressive disease, leading to destruction of the bile ducts, fibrosis, cirrhosis, portal hypertension and ultimately hepatic decompensation resulting in liver failure. 

Epidemiology of PSC

The pathogenic etiology and mechanism of PSC is unclear, but is often associated with inflammatory bowel disease (IBD) and ulcerative colitis, the latter of which affects approximately 75 percent of patients with PSC. The inflammatory infiltrate in PSC suggests that there are exogenous triggers that initiate the hepatic innate immune response, and accordingly, inflammatory cells are activated through secretion of cytokines and chemokines perpetuating an inflammatory reaction. Proinflammatory cytokines have been shown to directly affect the function of cholangiocytes.

PSC is a rare disease, estimated to affect fewer than 50,000 people in the United States.

Treatment

Currently there are no effective therapies for PSC. Ursodeoxycholic acid (UDCA) is the most studied therapy for PSC, and although several studies have shown that there is improvement in liver biochemistries, there is a long history of inconclusive trials failing to demonstrate positive clinical outcomes or increased transplant-free survival compared to placebo. Patients often require a liver transplant within 10-15 years of diagnosis. The prognosis is often poor for this progressive disease, with median survival of 12 years without a liver transplant.

Symptoms

Although many patients maybe asymptomatic, common symptoms include:

  • Jaundice
  • Puritus (itching)
  • Fatigue

Diagnosis

The steps and tests commonly used to diagnose and assess PSC are outlined below:

  • Medical history, physical and blood tests

A history review and physical is the usual starting point to diagnose PSC. Blood tests are used to examine liver function and inflammation. These tests include ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase, also abbreviated as ALK), GGT (gamma-glutamyltranspeptidase), and bilirubin.

  • ERCP

Endoscopic retrograde cholangiopancreatograph (ERCP) or magnetic resonance cholangiopancreatography (MRCP) are specialized procedures to examine your bile ducts and determine if, where, and to what extent they have become injured/affected as a result of PSC.

  • Colonoscopy

Because PSC is often associated with inflammatory bowel disease, especially ulcerative colitis, a colonoscopy may be recommended to see if you have this condition.

  • Liver biopsy

If the above have been performed but the diagnosis cannot be established or more information is needed, a liver biopsy may be pursued.

Current Activities

We are studying CVC, an investigational product, intended for the treatment of patients with PSC.

We are sponsoring a Phase 2a study of CVC

External Resources

You can find more information on PSC on these websites...

PSC Partners

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