What is primary sclerosing cholangitis (PSC)?

From the Guidelines

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation and scarring of the bile ducts, both inside and outside the liver, often associated with inflammatory bowel disease, particularly ulcerative colitis, and typically affecting adults between 30-50 years old with a male predominance. The disease leads to bile duct narrowing, causing bile to accumulate in the liver, resulting in liver damage and potentially cirrhosis. Symptoms include fatigue, itching, jaundice, abdominal pain, and weight loss, though some patients may be asymptomatic initially. Diagnosis involves blood tests showing elevated liver enzymes (particularly alkaline phosphatase), imaging studies like MRCP or ERCP showing characteristic "beaded" appearance of bile ducts, and sometimes liver biopsy 1.

Key Characteristics of PSC

• Chronic liver disease with inflammation and scarring of bile ducts
• Often associated with inflammatory bowel disease, particularly ulcerative colitis
• Typically affects adults between 30-50 years old with a male predominance
• Symptoms include fatigue, itching, jaundice, abdominal pain, and weight loss
• Diagnosis involves blood tests, imaging studies, and sometimes liver biopsy

Management and Treatment

• Currently, there is no curative medical treatment for PSC except liver transplantation for advanced disease
• Management focuses on treating symptoms and complications
• Ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day may help some patients by improving liver biochemistry, though its effect on disease progression remains controversial 1
• Cholestyramine can help manage itching
• Endoscopic procedures may be necessary to dilate strictures or remove stones
• Patients require regular monitoring for complications including cholangitis, dominant strictures, and cholangiocarcinoma, with surveillance colonoscopies recommended due to increased colorectal cancer risk in those with IBD 1

Future Directions

• Research priorities include diagnosis of PSC, diagnosis of cholangiocarcinoma in PSC, endpoint clarification, pathophysiology, and proof-of-concept clinical trials 1
• Novel technologies and large-scale assessments are needed to overcome gaps in understanding PSC pathophysiology
• Academic efforts should be maximized to improve the management of patients with PSC 1

From the Research

Definition and Characteristics of Primary Sclerosing Cholangitis (PSC)

• Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by multifocal strictures in the intra- and extrahepatic biliary tree 2.
• It is a chronic progressive disease, usually associated with underlying inflammatory bowel diseases (IBDs), with a prevalence of 60-80% in western countries 3.
• PSC causes obstruction of intra- and/or extra-hepatic bile ducts by inflammation and fibrosis, leading to biliary obstruction, cirrhosis and portal hypertension with all associated sequelae 4.

Clinical Approach and Management

• The medical treatment options for PSC associated with IBD do not differ from the cases of PSC alone, and include ursodeoxycholic acid and immunosuppressive agents 3.
• Liver transplantation is the only potential curative therapy for PSC with reported survival rates of 85 and 70% at 5 and 10 years after transplant 3.
• Endoscopic therapy, including endoscopic retrograde cholangiopancreatography (ERCP), is used to relieve cholestasis and perhaps also delay the development of liver cirrhosis 2.
• The 4-D approach to endoscopic evaluation and management of PSC includes dominant stricture diagnosis and evaluation, dilation of strictures, dysplasia and cholangiocarcinoma diagnosis, and dosing of antibiotics 4.

Complications and Risks

• Neoplastic transformation in primary sclerosing cholangitis is unpredictable 2.
• The incidence of cholangiocarcinoma is high in PSC patients, with a 398-fold increased risk compared to the general population 4.
• Early detection of cholangiocarcinoma in PSC remains a clinical challenge requiring a specialized diagnostic workup 5.
• Long-life annual surveillance colonoscopy is usually recommended for PSC-IBD patients due to the increased risk for malignancy, including colorectal cancer (CRC) 3.