PSC can affect any age group, and it has been described in most racial groups. It usually occurs among men twice as commonly as it does among women. The average age at diagnosis is the early forties, but the disease has been described in children as young as 1 year and adults as old as 90 years. When PSC occurs in children, however, the liver disease seems to share features with autoimmune hepatitis. The overlap of PSC and autoimmune hepatitis in adults occurs in 5% of patients. PSC can be identified in patients without symptoms who come into medical attention solely because of abnormal results of function tests. Symptoms such as jaundice, pruritus, abdominal pain, fever, and weight loss or manifestations of portal hypertension in advanced stages of liver disease are uncommon initial manifestations. Physical examination may be unrevealing. Hepatomegaly, splenomegaly, hyperpigmentation, and excoriation can be found, but patients are now coming to medical attention earlier with a diagnosis established before some of the physical findings of more advanced liver disease have developed. Health-related quality of life is significantly impaired among patients with PSC compared with individuals from the healthy population, although it is similar to other liver disease, such as primary biliary cirrhosis (PBC), and chronic infection with hepatitis B or C virus.
Chronic cholestasis of at least 6 months duration is the biochemical hallmark of PSC. Alkaline phosphatase is the most commonly elevated liver enzyme, usually to a higher level than aminotransferases, which are seldom more than 5 times normal. In children, however, aminotransferase levels may be markedly elevated. Serum bilirubin levels usually are normal, but they may be slightly elevated, and in patients with advanced PSC, they can reach very high levels. Hypergammaglobulinemia occurs in approximately 25% of patients, immunoglobulin M levels being the most commonly elevated component. About 80% of patients test positive for perinuclear antineutrophil cytoplasmic antibodies, but these antibodies can also be found in patients with PBC and autoimmune hepatitis, rendering this test nonspecific.
Typical cholangiographic findings of PSC include multifocal structuring and beading, usually involving the intrahepatic and extrahepatic biliary systems. Often the strictures are diffusely distributed and are short and annular. Cystic duct and gallbladder are affected in 15% of patients. The presence of gallbladder polypoid masses should raise the suspicion of gallbladder cancer.
Liver biopsy findings usually are not enough to establish a diagnosis of PSC. The classic onion-skin fibrosis may be seen in less than 15% of biopsy specimens but, when seen, is highly suspicious of PSC. The most commonly used histologic grading system, proposed by Ludwig and colleagues (1986), has the four following stages: stage 1, portal; stage 2, periportal; stage 3, septal; and stage 4, cirrhosis. Unfortunately, the histologic changes in patients with PSC seem to be quite varied from segment to segment of the same liver at any given point in time.
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