Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients have inflammatory bowel disease, most often ulcerative colitis. Other associated conditions include connective tissue disorders, autoimmune disorders, and immunodeficiency syndromes, sometimes complicated by opportunistic infections. Fatigue and pruritus develop insidiously and progressively. Diagnosis is by cholangiography (magnetic resonance cholangiopancreatography or ERCP). Liver transplantation is indicated for advanced disease.
PSC is the most common form of sclerosing cholangitis. Most (70%) patients with PSC are men. Mean age at diagnosis is 40 yr.
Although the cause is unknown, PSC is associated with inflammatory bowel disease, which is present in 80% of patients. About 5% of patients with ulcerative colitis and about 1% with Crohn disease develop PSC. This association and the presence of several autoantibodies (eg, anti–smooth muscle and perinuclear antineutrophilic antibodies [pANCA]) suggest immune-mediated mechanisms. T cells appear to be involved in the destruction of the bile ducts, implying disordered cellular immunity. A genetic predisposition is suggested by a tendency for the disorder to develop in multiple family members and a higher frequency in people with HLAB8 and HLADR3, which are often correlated with autoimmune disorders. An unknown trigger (eg, bacterial infection, ischemic duct injury) probably causes PSC to develop in genetically predisposed people.
Symptoms and Signs
Onset is usually insidious, with progressive fatigue and then pruritus. Jaundice tends to develop later. About 10 to 15% of patients present with repeated episodes of right upper quadrant pain and fever, possibly due to ascending bacterial cholangitis. Steatorrhea and deficiencies of fat-soluble vitamins can develop. Persistent jaundice harbingers advanced disease. Symptomatic gallstones and choledocholithiasis tend to develop in about 75% of patients. Some patients, asymptomatic until late in the course, first present with hepatosplenomegaly or cirrhosis. PSC tends to slowly and inexorably progress. The terminal phase involves decompensated cirrhosis, portal hypertension, ascites, and liver failure. The time from diagnosis to liver failure is about 12 yr.
Despite the association between PSC and inflammatory bowel disease, the two diseases tend to run separate courses. Ulcerative colitis may appear years before PSC and tends to have a milder course when associated with PSC. Similarly, total colectomy does not change the course of PSC.
The presence of both PSC and inflammatory bowel disease increases the risk of colorectal carcinoma, regardless of whether a liver transplantation has been done for PSC. Cholangiocarcinoma develops in 10 to 15% of patients.
PSC is suspected in patients with unexplained abnormalities in liver function tests, particularly in those with inflammatory bowel disease. A cholestatic pattern is typical: elevated alkaline phosphatase and γ-glutamyltransferase (GGT) rather than aminotransferases. Gamma globulin and IgM levels tend to be increased. Anti–smooth muscle antibodies and pANCA are usually positive. Antimitochondrial antibody, positive in primary biliary cirrhosis, is characteristically negative.
Imaging of the hepatobiliary system begins with ultrasonography to exclude extrahepatic biliary obstruction. Although ultrasonography or CT can show ductal dilation, diagnosis requires cholangiography to show multiple strictures and dilations in the intrahepatic and extrahepatic bile ducts. Cholangiography should begin with magnetic resonance cholangiopancreatography (MRCP). ERCP is usually a 2nd choice because it is invasive. Liver biopsy is usually not required for diagnosis; when done, it shows bile duct proliferation, periductal fibrosis, inflammation, and loss of bile ducts. With disease progression, periductal fibrosis extends from the portal regions and eventually leads to secondary biliary cirrhosis.
Measurement of serum tumor markers and ERCP surveillance with brush cytology should be done regularly to check for cholangiocarcinoma.
Asymptomatic patients usually require only monitoring (eg, physical examination and liver function tests twice/yr). Ursodeoxycholic acid (eg, 5 mg/kg po tid, up to 15 mg/kg/day) reduces itching and improves biochemical markers but not survival. Chronic cholestasis and cirrhosis require supportive treatment. Episodes of bacterial cholangitis warrant antibiotics and therapeutic ERCP as needed. If a single stricture appears to be the major cause of obstruction (a dominant stricture, found in about 20% of patients), ERCP dilation (with brush cytology to check for tumors) and stenting can relieve symptoms.
Liver transplantation is the only treatment that improves life expectancy in patients with PSC and that offers a cure. Recurrent bacterial cholangitis or complications of end-stage liver disease (eg, intractable ascites, portosystemic encephalopathy, bleeding esophageal varices) are reasonable indications for liver transplantation.
Last full review/revision November 2013 by Ali A. Siddiqui, MD
Content last modified November 2013