Immunologic effects of ursodeoxycholic acid in primary biliary cirrhosis

Investigations were undertaken to determine the effect on lymphocyte reactivity of treatment of primary biliary cirrhosis with ursodeoxycholic acid (UDCA). Eight patients with stage 2 and 6 with stage 3 primary biliary cirrhosis were observed. Patients were treated with 300 mg of UDCA three times daily for 1 to 3 years. UDCA reduced jaundice, pruritus, and serum alkaline phosphatase levels. Repeat liver biopsy showed a decrease in inflammation in 3 patients. One patient with stage 3 primary biliary cirrhosis had disease progression despite UDCA treatment. Phytohemagglutinin (PHA) and concanavalin A (con A) were added to mixed lymphocytes from 9 patients receiving UDCA before and after 1 year of treatment. T-cell reactivity was determined by evaluating tritiated thymidine incorporation into DNA. Patients exhibiting an improvement in liver function tests had a significant reduction in lymphocyte reactivity to these mitogens (P < .01). When UDCA was stopped, the response to PHA and con A returned to pretreatment levels, reflecting continued presence of immunologic abnormalities characteristic of primary biliary cirrhosis. UDCA's effect on lymphocyte reactivity appears to be due to a reduction of hydrophobic bile acids, since it does not alter response to mitogens in patients with a normal liver.