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How is primary sclerosing cholangitis treated?

Primary sclerosing cholangitis (PSC) is a chronic (lasting years and decades), progressive (worsening over time) disease of the bile ducts.
– This disease channelizes bile from the liver into the intestines.
– Bile is a watery liquid made by the cells of the liver that is important for digesting food in the intestine, particularly fat.
– This liquid also helps to get rid of the body of toxins.
– Liver cells secrete the bile they make into small canals within the liver.
– The bile flows through the canals and into larger collecting canals (ducts).
– The bile then flows within the intrahepatic bile ducts out of the liver and into the extrahepatic bile ducts.
– From the extrahepatic bile ducts, the bile flows into the intestine where the bile mixes with food.

In primary sclerosing cholangitis :
– The intrahepatic and extrahepatic bile ducts become inflamed,
– scarred and thickened (sclerotic),
– narrowed,
– finally obstructed.

Obstruction of the ducts can lead to:
– abdominal pain,
– itching,
– jaundice,
– infection in the bile ducts (cholangitis),
– liver scarring that leads to liver cirrhosis,
– liver failure.

Diagnosis of primary sclerosing cholangitis includes:
– Blood tests
– Radiologic tests
– Colonoscopy

The treatment of primary sclerosing cholangitis includes:
– Cholestyramine (Questran) or rifampin(Rifadin) to diminish itching.
– Antibiotics for infection, specifically cholangitis.
– Vitamin D and calcium to prevent bone loss (osteoporosis).
– Medications such as ursodiol (UDCA) to retard the progression of primary sclerosing cholangitis.
– ERCP with balloon dilatation.
– Stenting (a procedure in which the bile ducts are stretched open) for primary sclerosing cholangitis patients with dominant extra-hepatic duct strictures.
– Liver transplantation for patients with advanced cirrhosis.

Medications
– Ursodiol (UDCA),
– Prednisone,
– Methotrexate(Rheumatrex, Trexall),
– Colchicine,
– 6-mercaptopurine,
– Tacrolimus (Prograf),
– Cyclosporine (Neoral, Gengraf)

UDCA
– Ursodiol (UDCA) is a bile acid.
– This is given orally and replaces other bile acids in the body.
– UDCA is believed to protect against damaging effects of other bile acids on the liver cells.
– It also can induce formation of antioxidants.
– UDCA is the most extensively studied medication for primary sclerosing cholangitis.
– Its standard doses are15 mg/kg/day.
– It has been shown to improve fatigue, and improve blood levels of liver enzymes in these patients.
– Higher doses (20-30 mg/kg/day) UDCA has been shown to improve blood liver enzymes.
– It also decreases bile duct inflammation, and decrease liver scarring.
– UDCA is safe and well tolerated.
– It may improve bile duct disease and retard the development of liver cirrhosis.
– UDCA may decrease colon cancer risk in patients with both primary sclerosing cholangitis and chronic ulcerative colitis.

Treatment of dominant strictures
– Dominant strictures are major narrowing in the extrahepatic bile ducts.
– Dominant strictures of the extrahepatic bile ducts occur in 7%-20% of primary sclerosing cholangitis patients.
– ERCP and balloon dilatation (stretching) of the stricture can improve symptoms and abnormal blood levels of liver enzymes and bilirubin.
– Successful dilatation of dominant strictures decreases the risk of developing cholangitis.
– ERCP and dilatation of dominant strictures should be done in centers with highly experienced physicians.
– In ERCP, doctors often also perform brush cytology of the dominant strictures to exclude cholangiocarcinoma.
– Surgery is another treatment for dominant extrahepatic strictures.
– Surgical resection of the stricture followed by creation of a choledocho-jejunostomy which is an artificial passage for bile formed by attaching the bile duct from above the stricture directly into the small intestine.
– This can improve symptoms, delay liver transplantation, and lower the risk of cholangiocarcinoma.

Liver transplantation
The reasons for liver transplant in primary sclerosing cholangitis patients are similar to those in other forms of end-stage liver disease. They are:
– Internal bleeding due to rupture of esophageal varices.
– Severe ascites that are refractory to medical treatment.
– Frequent episodes of bacterial cholangitis.
– Hepatic encephalopathy.

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