We will investigate the immunological and genetic events involved in the development of primary biliary cirrhosis and will determine whether colchicine will favorably alter the course of this disease. Sixty patients with primary biliary cirrhosis (PBC) will be entered into a prospective double-blind study of colchicine versus placebo. The response to treatment will be evaluated by anaylsis of life table survival curves, observation of serial liver function tests and comparison of percutaneous liver biopsies done at 24-month intervals and read under code. We will apply the early stopping principal to the success rates in order to minimize the duration of the colchicine trial, in the event that colchicine should prove to be effective. We will perform HLA-DR typing of all PBC patients and their first degree relatives using the standard microlymphocytotoxicity assay. We will study in vitro antimitochondrial antibody production, suppressor cell function, and antilymphocyte antibodies in PBC patients and their first degree relatives and attempt to isolate and identify immunoregulatory factors responsible for the development of this disease. If there is a favorable response to colchicine, we will determine whether it correlates with normalization of suppressor cell function and a lowered titer of antilymphocyte antibodies. We will correlate histocompatibility antigens with suppressor cell function, response to therapy and presence of autoantibodies in patients and family members in an effort to determine the genetic factors necessary for the development of PBC.
