ABSTRACT
Primary biliary cirrhosis (PBC) is an immuno logically mediated disease in which activated
T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts
of genetically susceptible patients. This article reviews the results of treatment
of PBC with immunomodulatory agents. Results with drugs such as glucocor-ticoids,
azathioprine, and chlorambucil have been disappointing because of either limited efficacy
(azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved
tests of liver function in three prospective studies and was associated with improved
survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine
appears to slow the rate of progression of PBC but not to stop it. Preliminary results
suggest that colchicine may have synergistic effects if used together with ursodeoxycholic
acid, particularly in patients who are only partially responsive to ursodeoxycholic
acid. Results with cyclosporine have been disappointing because of limited efficacy
and predictable toxicity. The modest improvement in tests of liver function and survival
are counterbalanced by the development of hypertension in some and worsening renal
function in most. There is little beneficial effect on symptoms or histology. Results
with methotrexate are promising. There are improvements in symptoms and tests of liver
function that are equal to those seen with ursodeoxycholic acid and significant improvement
in liver histology. Some patients, particularly those with striking inflammation and
granulomas in portal triads, appear to have achieved sustained remission while on
methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic
acid in patients whose blood tests have responded only partially to ursodeoxycholic
acid. The most effective treatment of PBC will most likely use a combination of drugs
such as ursodeoxycholic acid, colchicine, and methotrexate.
KEY WORDS
primary biliary cirrhosis - cyclosporine - colchicine - methotrexate - azathioprine
- prednisone - treatment - immunomodulatory drugs
