COMMENTARY

The Challenges Surrounding Primary Sclerosing Cholangitis

Rowen K. Zetterman, MD

Disclosures

April 20, 2015

In This Article

A Disease That Often Overlaps With Several Conditions

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease that produces inflammation of the extrahepatic and/or intrahepatic bile ducts, thereby leading to bile duct stricturing, end-stage liver disease, and hepatic decompensation.[1] The incidence and prevalence rates for PSC have a reported range of up to 1.3 per 100,000 inhabitants annually and 16.2 cases per 100,000 inhabitants, respectively.[2] PSC typically affects young adults, with presentation often occurring before the age of 40 years.[3] There is an approximately 2-to-1 ratio of PSC occurrence in men to women.[2] Once the disease is established, the survival interval from diagnosis to transplantation or death ranges from 7 to 18 years.[3]

PSC is associated with inflammatory bowel disease in 70% of adult cases; inflammatory bowel disease can precede the onset of PSC, develop concurrently, or follow its diagnosis. Occasionally, inflammatory bowel disease does not occur until after liver transplantation for end-stage PSC. Approximately two thirds of patients with PSC and inflammatory bowel disease will have ulcerative colitis, which is often extensive or right-sided with rectal sparing and backwash ileitis. Crohn disease occurs with PSC in approximately 10% of cases. PSC has also been described in fibrosing disorders such as fibrosing parotitis, Reidel struma of the thyroid, orbital pseudotumor, mediastinal fibrosis, retroperitoneal fibrosis, retractile mesenteritis, or Peyronie disease as well as presumed autoimmune diseases, including autoimmune hepatitis, systemic lupus erythematosus, scleroderma, and celiac disease.[4]

PSC is less likely to develop during childhood and, when present, is often associated with inflammatory bowel disease. Both PSC and autoimmune hepatitis appear to be immune-mediated liver diseases. An overlap of both of these hepatic conditions can occur in children. Because serum alkaline phosphatase levels are elevated in children due to bone growth, measurement of gamma-glutamyltransferase should be used in children suspected of having biliary tract disease. Aminotransferases are more elevated in children with PSC than in adults. Dominant biliary strictures and cholangiocarcinoma are uncommon in childhood.[5,6]

In their published guidelines for the diagnosis and management of patients with PSC,[1] the American Association for the Study of Liver Diseases (AASLD) suggests the following diagnostic and treatment pathways for children with suspected PSC and/or autoimmune hepatitis:

  • A liver biopsy can be used to diagnose a suspected overlap syndrome between PSC and autoimmune hepatitis;

  • Children with overlap of PSC and autoimmune hepatitis should be treated with immunosuppressive agents;

  • Screening and surveillance procedures for biliary tract cancer in children with PSC need not be used;

  • Screening for colorectal cancer in patients with inflammatory bowel disease should not be influenced by the simultaneous diagnosis of PSC; and

  • Liver transplantation should be used for children with decompensated, end-stage liver disease from PSC.

Pathogenesis

The mechanism by which PSC develops is unclear. Both genetic predisposition and immune-mediated events may play a role.[7,8] When PSC occurs in families, first-degree relatives are more likely to develop disease.[9] Biliary cells of patients with PSC express HLA class II antigens[10] associated with accumulation of T cells and NK cells around the bile ducts. Circulating autoantibodies are common in PSC,[11] including anti-neutrophil cytoplasmic antibody (ANCA), perinuclear ANCA, anti-nuclear antibody, and anti-smooth muscle antibody. More than 80% of patients with PSC will have low circulating titers of up to three antibodies.[11]

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