What is Primary Sclerosing Cholangitis (PSC)?

From the Guidelines

Primary Sclerosing Cholangitis (PSC) is a chronic, progressive liver disease that requires a comprehensive management approach focusing on treating symptoms and complications, with liver transplantation being the only curative option. The diagnosis of PSC should be made in the presence of typical findings of sclerosing cholangitis on high-quality cholangiography, such as magnetic resonance cholangiopancreaticography (MRCP), and after exclusion of secondary causes 1.

Key Management Strategies

• Ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day may be used to improve liver biochemistry, although its effect on disease progression remains controversial.
• Cholestyramine (4-16 g/day) can help manage pruritus.
• Antibiotics like ciprofloxacin or metronidazole are used for bacterial cholangitis episodes.
• Endoscopic interventions, including balloon dilation or stent placement, are necessary for dominant strictures.
• Regular screening for complications, such as colonoscopy every 1-2 years for colorectal cancer and periodic imaging for cholangiocarcinoma, is crucial due to the strong association with inflammatory bowel disease, particularly ulcerative colitis.
• Fat-soluble vitamin supplementation (A, D, E, K) is recommended for patients with advanced disease.

Diagnostic Approach

The diagnosis of large duct PSC should be made in the presence of typical findings of sclerosing cholangitis on high-quality cholangiography, such as MRCP, and after exclusion of secondary causes 1. A diagnosis of small duct PSC should be considered in patients with elevated serum markers of cholestasis of unknown cause, normal high-quality cholangiography, and compatible histology of PSC, particularly in those with concomitant inflammatory bowel disease (IBD) 1.

Complications and Prognosis

PSC typically progresses slowly over years, with a median transplant-free survival of 12-21 years from diagnosis, though the course is variable and unpredictable. The disease pathogenesis involves immune-mediated damage to bile ducts, with genetic and environmental factors contributing to an abnormal immune response. Bacterial cholangitis is a significant complication in PSC, particularly in those with high-grade strictures, and requires prompt antibiotic treatment 1.

Recommendations

The use of MRCP as a diagnostic tool is strongly recommended due to its high sensitivity and specificity, as well as its non-invasive nature. Additionally, regular screening for complications and prompt treatment of bacterial cholangitis are crucial in managing PSC. The management of PSC should be individualized, taking into account the patient's specific needs and disease characteristics, as outlined in the EASL clinical practice guidelines on sclerosing cholangitis 1.

From the Research

Definition and Prevalence of Primary Sclerosing Cholangitis

• Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive destruction of the bile ducts 2, 3, 4, 5.
• The prevalence of PSC is estimated to be 4 to 16 cases per 100,000 persons, with a significant increase in incidence over the last 20 years 2.
• PSC tends to arise in patients with chronic inflammatory bowel diseases, such as ulcerative colitis 2, 3, 4.

Diagnosis of Primary Sclerosing Cholangitis

• The diagnosis of PSC is typically established with a bile duct imaging study, such as magnetic resonance cholangiopancreaticography (MRCP) or endoscopic retrograde cholangiography 2, 5.
• MRCP is more than 80% sensitive and more than 90% specific for the diagnosis of PSC 2.
• Cholangiography is considered the gold standard for diagnosis of PSC 4.

Treatment and Management of Primary Sclerosing Cholangitis

• Options for drug treatment are limited, and randomized, controlled trials have not shown any improvement of outcomes from the administration of ursodeoxycholic acid (UDCA) 2, 6.
• Interventional endoscopy is used to treat dominant stenoses and cholangitis, although this method of treatment is supported only by low-level evidence 2.
• Liver transplantation is a good option for patients with advanced PSC, resulting in a 10-year survival rate above 80% 2, 4.
• There is no causally directed treatment for PSC, and early diagnosis, complication management, and the evaluation of an optimally timed liver transplantation are the main determinants of outcome 2.

Complications and Prognosis of Primary Sclerosing Cholangitis

• PSC is associated with an increased risk of various types of cancer, most prominently cholangiocellular carcinoma (CCC) 2, 3, 5.
• The risk that a patient with PSC will die of cancer is 40% to 58% 2.
• The time from diagnosis to death or liver transplantation is 12 to 18 years 2.
• Patients with PSC are also at increased risk of colorectal cancer, particularly those with colitis 3, 5.