The pathophysiology of PSC is unclear, but there is evidence suggesting an autoimmune component to the disease. There is also a genetic predisposition, with an increased prevalence of HLA-B2 and DR3 in patients with PSC. Other proposed causes include chronic portal bacteremia, cytotoxic bile acids, and viral infections.
Currently, no medical therapy has been shown to be beneficial in PSC. A 2-year randomized, controlled trial using UDCA at a dose of 12 to 15 mg/kg/d in patients with PSC was associated with improved liver tests, however there was no beneficial effect on survival, liver histology, cholangiographic appearance or symptoms.
Liver transplantation is effective for patients who have evidence of end-stage liver disease or who have recurrent bouts of cholangitis that cannot be controlled with dilation of a dominant stricture. Unfortunately, PSC recurs in 15% to 20% of cases, and recurrence is often associated with loss of the graft. Currently, no medical therapy has been shown to be beneficial in PSC.