Primary Sclerosing Cholangitis -- Approach to Diagnosis

Ian L. Steele, MD; Cynthia Levy, MD; Keith D. Lindor, MD


April 25, 2007

Laboratory Studies

Elevated serum ALP is the most common laboratory abnormality seen in PSC. ALP levels are often found to be 3 to 10 times the upper limit of normal, whereas serum AST and ALT levels are typically 2-3 times the upper limit of normal.[9,10] The majority of patients with PSC have a normal serum total bilirubin level. An increase in bilirubin may result from stricturing due to advanced disease, acute cholangitis, choledocholithiasis, or development of malignancy. As with most liver diseases, altered prothrombin time and serum albumin levels reflect progression of disease.[3,6,11,17]

Changes in immunologic markers are not unusual. Serum immunoglobulin levels are frequently elevated, particularly IgG and IgM. Although serum IgG4 levels are usually within normal limits, approximately 9% of patients can present with elevated IgG4 (> 140 mg/dL).[18] These patients differ from those with normal serum IgG4 levels in that they have a lower frequency of associated IBD, higher PSC Mayo risk scores, and shorter time to liver transplantation, possibly representing a more severe course of disease. The pancreatogram may be abnormal in these patients, causing confusion with another entity known as autoimmune sclerosing pancreatitis.[19,20,21] Additional studies are needed to better define diagnostic criteria and to determine whether this subgroup of patients with PSC and increased IgG4 levels will respond similarly to steroid therapy as patients with autoimmune sclerosing pancreatitis.

As many as 97% of patients with PSC have at least one detectable autoantibody;[22] however, the presence of multiple antibodies does not correlate with disease activity.[23] Anti-smooth muscle antibodies and antinuclear antibodies are found in up to 75% of patients with PSC.[24] But when antimitochondrial antibodies are detected, consideration should be given to primary biliary cirrhosis as a more likely diagnosis. Cases of PSC-primary biliary cirrhosis overlap have been described, although exceedingly rare.[25,26,27] Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) has been described in up to 80% of patients with PSC, as well as in 30% of their unaffected family members.[28] P-ANCA in PSC appears to be unrelated to ulcerative colitis, as it may be seen in patients with PSC without ulcerative colitis. Recent investigation has shown that antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA) are found in up to 44% of patients with PSC irrespective of the presence of IBD,[23] but its significance is yet to be determined.

Gastroenterologists frequently use serum CA 19-9 as a screening test for cholangiocarcinoma in patients with PSC. However, this tumor marker is not specific for cholangiocarcinoma and levels can be elevated in many circumstances, including both malignant and benign conditions. Thus, an abnormal serum CA 19-9 level can be found not only in patients with cholangiocarcinoma, pancreatic cancer, and hepatocellular carcinoma, but also in those with PSC without cancer, alcoholic liver disease, cholangitis, autoimmune hepatitis, chronic viral hepatitis, and pancreatitis. We have previously evaluated the utility of CA 19-9 as a screening tool in patients with PSC and found that a serum value > 129 U/mL could adequately differentiate between benign and malignant strictures with a sensitivity of 78.6% and specificity of 98.5%. These numbers were in agreement with data reported by other investigators. However, the positive predictive value was only 56.6%, and almost all cases of cholangiocarcinoma that had an elevated CA 19-9 level were too advanced to qualify for any curative treatment. These findings suggest that serum CA 19-9 does not perform well as a screeningtest. Other diagnostic modalities are needed to identify patients who could benefit from early intervention.[29]


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