Primary Sclerosing Cholangitis
Primary sclerosing cholangitis is an idiopathic, cholestatic liver disease that is caused by chronic inflammation and fibrosis medium and large bile ducts. About half of patients do not have symptoms at the time of diagnosis, but are discovered by abnormal liver function tests. When symptoms are present, they usually include right upper quadrant abdominal pain, pruritus, jaundice and fatigue. Physical exam may reveal jaundice, hepatomegaly, splenomegaly and excoriations.
Liver enzymes reveal a cholestatic pattern with a predominant elevation of serum alkaline phosphatase. Serum ALT and AST are usually less than 300 IU/L. Alkaline phosphatase and bilirubin may fluctuate over time due to transient blockage of bile ducts by biliary sludge or small stones. Serum albumin concentration is often normal in the early stage of disease, but decreases with progressive inflammation. Additional laboratory findings include polyclonal gammopathy and atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA). Anti-mitochrondrial antibodies, which are characteristic of primary biliary cholangitis, are usually not detected.
Diagnostic criteria include an increased serum alkaline phosphatase level that persists for more than 6 months, cholangiographic findings of bile-duct strictures, and exclusion of causes of secondary sclerosing cholangitis. Liver biopsy is usually not necessary for diagnosis unless small-duct primary sclerosing cholangitis or autoimmune hepatitis is suspected.
Patients with primary sclerosing cholangitis often have coexisting ulcerative colitis. The risk of colon cancer in patients with primary sclerosing cholangitis and ulcerative colitis is four times higher than in patients with inflammatory bowel disease alone.
Primary sclerosing cholangitis is the most common risk factor for cholangiocarcinoma. Median survival after diagnosis is 10 to 12 years. Approximately 40% of patients with primary sclerosing cholangitis ultimately require liver transplantation. After liver transplantation, the 5-year survival rate is approximately 72%. Primary sclerosing cholangitis recurs in approximately 25% of patients after transplantation.
