What is the diagnosis and treatment for Primary Sclerosing Cholangitis (PSC)?

From the Guidelines

Primary sclerosing cholangitis (PSC) is a chronic liver disease that requires a multidisciplinary approach to manage symptoms and complications, with liver transplantation being the only definitive treatment for advanced disease. The condition is characterized by inflammation and scarring of the bile ducts, both inside and outside the liver, leading to bile duct narrowing and liver damage. According to the most recent guidelines 1, the treatment of PSC focuses on managing symptoms and complications, with ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day being prescribed to improve liver biochemistry, although its effect on disease progression remains uncertain.

Management of Symptoms and Complications

• Pruritus can be managed with bezafibrate or rifampicin, as recommended by the EASL clinical practice guidelines 1.
• Endoscopic procedures like ERCP may be required to dilate strictures and improve bile flow, with balloon dilation being the preferred method 1.
• Antibiotics are used to treat cholangitis episodes, typically with broad-spectrum coverage, such as third-generation cephalosporins, ureidopenicillins, carbapenems, and fluoroquinolones 1.
• Patients require regular monitoring for complications, including cholangiocarcinoma, and should undergo colonoscopy screening due to the high association with inflammatory bowel disease.

Treatment of Pruritus

• Bezafibrate is recommended as the first-line pharmacological treatment for moderate to severe pruritus in PSC, due to its sustained antipruritic effect and strong additive anticholestatic effects when combined with UDCA 1.
• Rifampicin may be used as a second-line treatment, but it may induce drug-induced hepatitis after 4-12 weeks in up to 12% of cholestatic patients 1.
• Naltrexone may be used as a third-line treatment, but starting at very low doses (12.5 mg) is recommended to avoid early side effects resembling an opioid withdrawal syndrome 1.

Importance of Multidisciplinary Approach

• PSC patients should be treated in a tertiary hospital to facilitate a multidisciplinary approach without jeopardizing future transplantation 1.
• A multidisciplinary team, including hepatologists, gastroenterologists, radiologists, and surgeons, is essential to manage the complex symptoms and complications of PSC.

From the Research

Definition and Characteristics of Primary Sclerosing Cholangitis

• Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis 2.
• PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40 2.
• Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC 2, 3.

Diagnosis and Clinical Presentation

• PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD 2.
• When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue 2, 4.
• Cholangiography is the gold standard for diagnosis of PSC, with typical radiologic findings including multifocal strictures and dilation involving the intrahepatic or extrahepatic biliary tract, or both 3, 4.

Management and Treatment

• Management of PSC is mainly focused on treatment of symptoms and addressing complications, as no effective medical therapy for halting disease progression has been identified 2, 5.
• Ursodiol (ursodeoxycholic acid) has been tested as a potential treatment, but studies have shown no significant clinical benefit 5.
• Liver transplantation is a good option for patients with advanced PSC, although the disease can recur after successful transplantation 2, 3, 4.
• Endoscopic treatment of symptomatic biliary strictures and evaluation of dominant strictures are also part of the management strategy 4.

Complications and Prognosis

• PSC can be complicated by bacterial cholangitis, dominant strictures, gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy 2.
• CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC 2.
• Patients with PSC have a markedly increased risk of cancer, notably including cholangiocarcinoma and gallbladder and colorectal cancers (particularly in patients with colitis) 4, 6.