The Challenges Surrounding Primary Sclerosing Cholangitis

Accompanying Disorders and Complications

Bacterial cholangitis occurs in PSC associated with right upper quadrant pain and tenderness, fever, chills, elevated aminotransferases, and cholestatic enzymes.

The AASLD guidelines suggest:

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  PSC patients with recurrent bacterial cholangitis should be considered for long-term antibiotic therapy; and
  
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  PSC patients with refractory bacterial cholangitis should be considered for liver transplantation.
  

Overlap disorders between autoimmune hepatitis and PSC are more likely in children and young adults. Between 1.4% and 17% of PSC patients will have simultaneous autoimmune hepatitis and PSC. Patients may have clinical manifestations of both diseases, including cholestasis and high aminotransferases. If an overlap of these disorders is considered possible, liver biopsy should be performed to establish a diagnosis, with subsequent treatment of autoimmune hepatitis using corticosteroids or other immunosuppressive therapy.

PSC can be associated with a number of complications. The prevalence of osteopenia in PSC increases with older patient age and greater disease severity.

The AASLD guidelines suggest:

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  Bone density studies should be used to exclude osteopenia at diagnosis of PSC and every 2-3 years thereafter;
  
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  If osteopenia is confirmed, 1.0-1.5 g of calcium and 1000 IU of vitamin D per day are recommended;
  
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  If osteoporosis is present, the use of bisphosphonate therapy in addition to calcium and vitamin D supplementation should be considered; and
  
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  In patients who have concurrent esophageal varices and osteoporosis, parenteral forms of bisphosphonates should be used.
  

Portal hypertension with ascites, esophagogastric varices, and hepatic encephalopathy can occur in end-stage PSC. Varices may develop in patients lacking cirrhosis due to portal fibrosis and portal venous occlusion. Nodular regenerative hyperplasia has also been described. Low circulating platelet counts can be a predictor of varices in PSC. Patients with PSC and an ileostomy following colectomy can develop peristomal varices and bleeding. Patients with end-stage PSC and decompensation should be considered for liver transplantation.

Cholangiocarcinoma occurs in 5%-10% of PSC patients with large-duct disease and is often found shortly after an initial clinical diagnosis of PSC. It is important to maintain a suspicion that cholangiocarcinoma may have developed if the patient with PSC experiences any clinical changes. Worsening liver tests, elevation of serum carbohydrate antigen 19-9, progressive clinical decompensation or jaundice, cholangitis, or worsening portal hypertension may all be signs of cholangiocarcinoma. Carbohydrate antigen 19-9 levels can be helpful but are not diagnostic of the presence of cholangiocarcinoma.

The AASLD guidelines suggest:

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  Patients with PSC should be evaluated for cholangiocarcinoma with clinical or biochemical deterioration;
  
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  Surgical resection of cholangiocarcinoma should be considered in PSC patients lacking cirrhosis; and
  
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  Liver transplantation can be considered for patients with early cholangiocarcinoma not amenable to surgical resection.
  

Gallbladder disease frequently occurs in patients with PSC. Gallstones, polyps, gallbladder wall thickening, and other changes suggesting involvement by sclerosing cholangitis may occur. As gallbladder polyps in patients with PSC have a higher risk for malignancy, periodic ultrasound evaluation is suggested followed by cholecystectomy when a gallbladder polyp is identified.

The AASLD guidelines suggest:

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  Annual ultrasound in patients with PSC to detect mass lesions of a gallbladder; and
  
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  Cholecystectomy as treatment for a gallbladder mass lesion regardless of lesion size, if underlying liver disease permits.
  

Inflammatory bowel disease is commonly associated with PSC; approximately 70% of patients will have ulcerative colitis and 10% will have Crohn disease. Patients with PSC and ulcerative colitis have a greater risk for mucosal dysplasia and colon cancer, which may be as much as 10-fold higher than patients with ulcerative colitis alone. Patients with PSC and Crohn colitis also have a greater risk for colon cancer. Even patients with PSC but without inflammatory bowel disease have an increased risk for colon cancer than age- and sex-matched adults without PSC.

The AASLD guidelines suggest:

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  Colonoscopy with mucosal biopsies should be completed at the time of diagnosis of PSC if there is no prior history or symptoms of inflammatory bowel disease; and
  
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  Those patients with both PSC and inflammatory bowel disease should have surveillance colonoscopy every 1-2 years.
  

Hepatocellular carcinoma may develop in patients with PSC who have cirrhosis. Periodic ultrasound surveillance and alpha-fetoprotein measurement should be completed in these patients.