Overall Bottom Line

PSC is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary system that can result in the formation of multifocal biliary strictures.
Though the etiology of the disease remains elusive, evidence suggests the role of genetic and immunologic factors.
Disease progression varies from patient to patient; the disease can result in complications of ESLD, portal hypertension, cholangitis and/or the development of cholangiocarcinoma.
While the majority of patients with PSC have or develop IBD (70–90%; mainly ulcerative colitis), a minority of patients with IBD have or will develop PSC (2.4–7.5%).
No specific therapy is of proven benefit and treatment is supportive. Liver transplantation is a viable option and should be considered early for those that have complications of their disease.

Section 1: Background

Definition of disease

PSC is a chronic progressive fibro-obliterative bile duct inflammation that can involve any part of the biliary tree.

The exact etiology of PSC remains unknown and multiple factors likely play a role.
Immune-mediated injury to the bile ducts may be responsible.
Other factors including bacteria, viruses, toxic bile acids, ischemia or environmental factors may precipitate the occurrence of this disease in an otherwise genetically susceptible individual.

The characteristic lesion seen on liver histology is an onion skin-type periductal fibrosis. The duct eventually degenerates and disappears leaving a bile duct scar. Depending on the disease severity, portal fibrosis becomes more pronounced and biliary cirrhosis develops.

Risk factor	Frequency amongst affected individuals
Male gender	70%
IBD (pancolitis > distal colitis)	70–90%
HLA B8	60–80%

No medical intervention has been demonstrated to prevent the disease.
The lifetime risk of developing cholangiocarcinoma is around 10%. Unfortunately lack of good surveillance tools limits early detection of cholangiocarcinoma.
The increased risk of gall bladder cancer and colorectal tumors leads to the recommendation of annual US and periodic colonoscopies.

Any patient with a repeatedly abnormal cholestatic pattern of liver chemistries should be evaluated. Likewise, patients with IBD and abnormal liver chemistries should be evaluated for PSC though only 2.4–7.5% will have or develop PSC.

Most patients with PSC present with abnormal liver chemistries in a cholestatic pattern though some will present with complaints of pruritus.
Rarely patients will be diagnosed with PSC after a bout of cholangitis or after presenting with ESLD or cholangiocarcinoma.
The physical examination findings of PSC are non-specific.
The diagnosis is typically established using cholangiographic techniques to define the biliary tract anatomy.
Rarely the diagnosis is made by finding characteristic “periductal” fibrosis on liver histology and normal cholangiography (i.e. small duct PSC).

Differential diagnosis	Features
AIDS cholangiopathy	History of positive HIV antibody differentiates
Bile duct neoplasm	Can be difficult to distinguish. Brushings and biopsy of the bile duct make the diagnosis
Biliary tract surgery	History of prior biliary surgery
Choledocholithiasis	History of pain and differences in cholangiographic appearance
Congenital abnormalities	Cholangiography should be able to differentiate
Ischemic injury to the bile duct	History of ischemic injury
Caustic injury – excluding chemotherapy	History of caustic injury
IgG4 sclerosing cholangitis	Distinguished based on laboratory testing and history of pancreatitis