Primary Sclerosing Cholangitis

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Primary Sclerosing Cholangitis

A chronic cholestatic syndrome characterized by fibrosing

inflammation in the intrahepatic and extrahepatic bile ducts leading

to narrowing and, eventually, obliteration of the bile ducts and

development of cirrhosis.

Etiology

The cause of primary sclerosing cholangitis (PSC) is unknown.

Theoretic pathogens include toxins, infectious agents, and

abnormalities in immune regulation. Although excess copper has been

implicated, patients have not responded to chelation with

penicillamine, suggesting that elevated hepatic copper levels are a

secondary phenomenon (as in primary biliary cirrhosis). Although both

cytomegalovirus and reovirus type 3 may affect the intrahepatic bile

ducts, there is little evidence that these viruses are present in all

patients with PSC. Altered immune mechanisms appear to be the most

likely cause; HLA-B8 and HLA-DR3, often found in autoimmune diseases,

have also been associated with PSC. Destruction of the bile ducts in

PSC involves T lymphocytes, and alterations in many arms of the

immune system have been noted.

Symptoms and Signs

PSC occurs most often in young men and is commonly associated with

inflammatory bowel disease, especially ulcerative colitis. The onset

is usually insidious, with gradual, progressive fatigue, pruritus,

and jaundice. Episodes of ascending cholangitis with right upper

quadrant pain and fever are uncommon. Some patients present with

hepatosplenomegaly or features of cirrhosis. The terminal phase is

characterized by decompensated cirrhosis, portal hypertension,

ascites, and liver failure.

Diagnosis

Most patients with PSC have elevated serum alkaline phosphatase,

which may be accompanied by mildly increased transaminase. Serum

bilirubin elevation is variable. Unlike in primary biliary cirrhosis,

in PSC the mitochondrial antibody test is negative. PSC is most

readily diagnosed by direct cholangiography, preferably ERCP.

Multiple short strictures and saccular dilations involving the

intrahepatic and extrahepatic bile ducts give the biliary tree an

irregular beaded appearance. The diagnosis is also supported by liver

biopsy findings, which show bile duct proliferation, periductal

fibrosis, inflammation, and loss of bile ducts. As the disease

progresses, fibrosis extends from the portal regions and eventually

leads to biliary cirrhosis.

Prognosis and Treatment

Some patients may be asymptomatic for many years. Such cases may

require only monitoring (eg, routine examination, liver examination,

and liver biochemistry twice per year). In general, the disease is

progressive. Supportive management is indicated for symptoms of

chronic cholestasis (see under Jaundice in Ch. 38) and for

complications of cirrhosis (see Ch. 41). Recurrent bacterial

cholangitis is treated with antibiotics as needed. Dominant

strictures may be managed by endoscopic or transhepatic dilation,

with or without stent placement. Proctocolectomy for patients with

ulcerative colitis is not effective in treating PSC. Corticosteroids,

azathioprine, penicillamine, and methotrexate have variable results

and are associated with significant toxicity. Ursodeoxycholic acid

may reduce itching and improve biochemical parameters but has not

been shown to alter the natural history of the disease. Liver

transplantation is the only apparent cure.

Of patients with PSC, 7 to 10% develop cholangiocarcinoma. The

optimal timing of transplantation to prevent this complication is

unknown.