Primary Sclerosing Cholangitis
GENERAL PRINCIPLES
Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder characterized by inflammation, fibrosis, and obliteration of the extrahepatic and/or intrahepatic bile ducts.
• PSC can be subdivided into small duct and large duct disease. Small duct disease is defined as typical histologic features of PSC with a normal cholangiogram. In large duct disease or classic PSC, typical “beads on a string” strictures of the biliary tree can be detected by cholangiography. Small duct disease carries a more favorable prognosis.15
• The peak incidence is at about age 40 years. Most patients are middle-aged men, and the male-to- female ratio is 2:1.
• PSC is frequently associated with IBD (70% of patients have concomitant UC). The clinical course of these conditions is not correlated.
• PSC increases the risk of colon cancer, in addition to the risk conferred by IBD alone.
DIAGNOSIS
Clinical Presentation
• Clinical manifestations include intermittent episodes of jaundice, hepatomegaly, pruritus, weight loss, and fatigue. Patients may also present with acute cholangitis.
• Acute cholangitis is defined as an infection of the biliary ductal system usually caused by bacteria ascending from its junction with the duodenum and is a frequent complication in patients with strictures of the biliary ducts. Symptoms of acute cholangitis include fever, chills, rigors, jaundice, and right upper quadrant pain.
• Cholangiocarcinoma is the most frequent neoplasm associated with PSC. Patients with PSC have a 10%-15% lifetime risk of developing cholangiocarcinoma.
• Secondary causes of sclerosing cholangitis and IgG4 associated cholangitis/autoimmune pancreatitis must be ruled out.
Diagnostic Testing
• The diagnosis of PSC should be considered in individuals with IBD who have increased levels of ALP even in the absence of symptoms of hepatobiliary disease.
• ANA is positive in up to 50% of cases, and perinuclear antineutrophil cytoplasmic antibody is positive in 80% of cases.
• MRCP is the preferred diagnostic study of choice.
DIAGNOSTIC PROCEDURES
• ERCP is a therapeutic procedure in patients with PSC when acute cholangitis is suspected. It is also performed when a dominant (severe) stricture is seen on MRCP to obtain duct brushings and biopsies to evaluate for cholangiocarcinoma. Sending brushings for fluorescence in situ hybridization may aid in the diagnosis of cholangiocarcinoma. Intraductal endoscopy, specifically cholangioscopy, can provide direct visualization of the biliary ducts with the advantage of direct tissue sampling.
• Liver biopsy is helpful in the diagnosis of small duct PSC, by excluding other diseases, and in staging. Characteristic histologic findings include concentric periductal fibrosis (“onion skinning”), degeneration of bile duct epithelium, ductular proliferation, ductopenia, and cholestasis.
TREATMENT
Medications
• At this time, there is no established medical treatment for PSC.
• Several randomized, placebo-controlled trials comparing the use of UDCA (13-23 mg/kg/d) to placebo showed improvement of LFTs in the UDCA group. However, there was no difference in long-term survival or time to liver transplantation. UDCA (gt;28 mg/kg/d) was associated with a higher risk of serious adverse events including death and transplantation and is not currently recommended for PSC.16
• Episodes of cholangitis should be managed with IV antibiotics and endoscopic therapy.
Nonpharmacologic Therapies
• ERCP can dilate and stent dominant strictures but does not mitigate disease progression.
• Surgical management
î Colectomy for UC does not affect the course of PSC.
î Patients with decompensated cirrhosis or recurrent cholangitis should be referred for liver transplantation. Recurrent PSC after liver transplantation has been documented.
î Selected hilar cholangiocarcinomas may be considered for liver transplantation.
î Gallbladder polyp follow-up should be comanaged with a liver or GI specialist.