Primary sclerosing cholangitis (PSC) is a progressive chronic inflammation of both the intrahepatic and extrahepatic bile ducts. The exact etiology is unknown but there is a strong association with autoimmune diseases, particularly ulcerative colitis (UC). In the early stages, PSC is often asymptomatic. As the disease progresses, patients may present with right upper quadrant abdominal pain, pruritus, fatigue, and weight loss. Laboratory tests show findings of cholestasis, including elevated alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT). While not recommended for diagnosis, pANCA is positive in up to 80% of cases. Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) is used for diagnostic confirmation. Management is primarily symptomatic, with liver transplantation reserved for end-stage liver disease.
- The exact cause is unknown.
- Chronic inflammatory bowel diseases (IBD)
- Presence of HLA-B8 and HLA-DR3
- Other autoimmune conditions (e.g., hypergammaglobulinemia IgM)
The majority of patients with PSC also have ulcerative colitis.References:
- Often initially asymptomatic
- Signs of cholestasis
- Later stages: signs of
- Symptoms of chronic , which is frequently associated with PSC, or other associated comorbidities
- Suspect PSC in patients with persistently elevated .
- Obtain abdominal imaging (e.g., ultrasound) to evaluate for .
- Obtain further studies for diagnostic confirmation.
Laboratory studies 
- : normal or moderately elevated (approx. 2–3× ULN) AST and ALT 
- : ↑ total cholesterol 
- CBC: Thrombocytopenia may be a sign of cirrhosis.
Findings are typically nonspecific but may help support the diagnosis or differential diagnoses.
|Serological studies in patients with suspected PSC |
All patients should be tested for elevated IgG4 at least once, as findings may influence management. 
Obtain abdominal imaging for all patients to evaluate for.
- Modalities: ultrasound, CT scan with contrast, MRI
- Supportive findings
Obtain for all patients for diagnostic confirmation.
- Magnetic resonance cholangiopancreatography
- Endoscopic retrograde cholangiopancreatography
Liver biopsy 
Differential diagnoses of cholestatic biliary disease
|Primary sclerosing cholangitis|| |
Secondary sclerosing cholangitis 
|Epidemiology|| || || |
|Pathophysiology|| || |
|Clinical presentation|| |
|Associated conditions|| || |
The differential diagnoses listed here are not exhaustive.
General principles 
- Management is primarily supportive and includes:
- cholestyramine , e.g., with
- Interventional treatment as needed to relieve obstructions
- Monitoring for commonly associated conditions and complications
- No medications currently prevent disease progression (e.g., reduced time to liver transplantation). 
- Liver transplantation is the only curative treatment but has a significant risk of disease recurrence.
Pharmacological management 
- Ursodeoxycholic acid (UDCA)
Immunosuppressants (e.g., glucocorticoids); usually reserved for patients with overlap syndromes: 
Interventional treatment 
Perform as needed in patients with relevant strictures. 
- ERCP with dilation of stenoses
- Indication: patients who cannot undergo ERCP
- Requires placement of a percutaneous drain
Liver transplantation 
- Refer patients with decompensated cirrhosis and a MELD score > 14.
- Additional MELD points may be offered to patients with:
Screening and monitoring 
|Screening and monitoring of complications and comorbidities in PSC |
|Inflammatory bowel disease|
|Gallbladder carcinoma|| || |
|Progression of liver disease|| |
|Osteoporosis|| || |
|Complications of cirrhosis ||Hepatocellular carcinoma|| || |
|Esophageal varices|| || |
Patients with both PSC and UC have a 4–5 times higher risk of developing colorectal dysplasia or cancer than those with UC alone. 
- Steatorrhea and deficiency of fat-soluble vitamins
- Liver cirrhosis
- Bacterial cholangitis
We list the most important complications. The selection is not exhaustive.
- Five-year survival rate after liver transplantation: ∼ 85%