Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation, destruction
and fibrosis of the intrahepatic and extrahepatic bile ducts that leads to cirrhosis of the liver. PSC is often complicated by recurrent episodes of bacterial cholangitis (infection of the bile ducts with bacteria). Patients with PSC also have an increased risk of cholangiocarcinoma (bile duct cancer). The cause of PSC is unknown but many investigators suspect that it is an autoimmune disease. Other etiologies, such as infectious agents, toxins or recurrent infections of the bile ducts are also possible causes. PSC has a worldwide prevalence of approximately 3/100,000. About 70 % of patients are men and about 75% of patients with PSC have inflammatory bowel disease, mainly ulcerative colitis. The mean age of diagnosis is around 40 years.
Most patients with PSC are diagnosed by discovering elevated serum alkaline phosphatase and gammaglutamyltranspeptidase activities on biochemical testing for other reasons (e. g. during evaluation of inflammatory bowel disease). Some patients present with pruritus (itching), jaundice (yellow skin caused by bilirubin retention), fatigue, fever, weight loss or signs of advanced liver disease. Patients can also present with signs and symptoms indistinguishable from those of acute bacterial cholangitis such as fever, chills and right upper quadrant abdominal pain.
Laboratory tests in PSC usually show elevated serum alkaline phosphatase and gammaglutamyltranspeptidase activities with slight elevations in serum aminotransferase activities. Early in the disease, the serum bilirubin concentration is usually normal or slightly elevated but it becomes markedly elevated late in the course. Sometimes, large fluctuations in serum bilirubin concentration can occur, even early in the disease, possibly as a result of transient bile duct obstruction or superimposed bacterial cholangitis. Early in the course of the disease, the serum albumin concentration and prothrombin time are normal. Later, when cirrhosis develops, the albumin concentration falls and the prothrombin time can be prolonged. The prothrombin time can also be prolonged prior to the development of cirrhosis secondary to decreased vitamin K absorption, in which case it will correct with the administration of parenteral vitamin K. About 30 % of patients with PSC have elevated serum gamma-globulin concentrations and about half have elevated serum IgM concentrations. About half of patients have serum antibodies against a perinuclear antigen in neutrophil cytoplasm (ANCA) and fewer have anti-smooth muscle (actin) or antinuclear antibodies. Some HLA haplotypes are also associated with PSC. As mentioned above, about 75 % of patients with PSC have inflammatory bowel disease, usually ulcerative colitis. The diagnosis of PSC is made by endoscopic retrograde cholangiopancreatography (ERCP). The characteristic findings include multifocal strictures and dilatations of the intrahepatic and extrahepatic bile ducts. Liver biopsy is usually confirmatory but not diagnostic. Liver biopsy is also important in determining if the patient has cirrhosis. Biopsy findings include degeneration of bile duct epithelial cells, infiltration of bile ducts with lymphocytes and neutrophils, "onion skin" lesions (concentric layers of fibrosis tissue surrounding a bile duct), periportal fibrosis, piecemeal necrosis, portal to portal fibrosis, loss of bile ducts, changes of cholestasis and frank cirrhosis. The "onion skin" lesion is diagnostic but is not usually seen.
Secondary causes of sclerosing cholangitis must be ruled out when making the diagnosis of PSC. Causes of secondary sclerosing cholangitis include drugs, bile duct cancers, past biliary tree surgery and opportunistic infections of the bile ducts that can cause a similar picture in patients with AIDS. These causes of secondary sclerosing cholangitis can usually be ruled-out by history, physical examination and laboratory tests.
PSC is a progressive disease that leads to cirrhosis and liver failure. The median survival, or time to liver transplantation, is around ten years from the time of diagnosis. The course of disease is usually complicated by recurrent bouts of superimposed bacterial cholangitis. A very high serum bilirubin concentration, complications of cirrhosis, older age and anemia indicate a poor prognosis and suggest that the patients should be referred for orthotopic liver transplantation.
Current medical therapy does not have a significant impact on slowing the progression of PSC but has an important role in the treatment of complications. Ursodiol improves laboratory parameters but it probably does not prolong survival or time to referral for liver transplant. Pruritus (itching) is a frequent complication that can be treated with bile acid-binding resins such as cholestyramine and opioid antagonist.
Deficiencies in fat-soluble vitamins are treated by supplementation. Aggressive antibiotic therapy is necessary to treat episodes of bacterial cholangitis. There may be some role for endoscopic dilatation of dominant bile duct strictures in some cases but there have been no controlled clinical trials. If such a procedure is contemplated, a physician with considerable experience in treating patients with PSC should be consulted. As there is an increased incidence of cholangiocarcinoma in patients with PSC, this should
always be suspected, especially in patients with long-standing disease whose condition worsens. Orthotopic liver transplantation is highly effective in the treatment of patients with advanced liver disease caused by PSC. Indications for liver transplantation include complications of cirrhosis such as bleeding esophageal varices, refractory ascites, encephalopathy and severe hepatic synthetic dysfunction. Patients with recurrent episodes of bacterial cholangitis and PSC should also be considered for orthotopic liver transplantation.