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Purpose: The presence of antimitochondrial antibodies (AMA), the hallmark of primary biliary cirrhosis (PBC), precedes the clinical manifestation of the disease for many years. The main mitochondrial autoantigen is the E2 component of the pyruvate dehydrogenase complex (PDC). The aim of this study was to identify anti-PDC-positive persons from two Estonian populations by different methodologies and to follow up the positive cases., Methods: Enzyme-linked immunosorbent assay (ELISA) tests for antibodies to native PDC and recombinant PDC-E2 fusion protein were performed in 1461 persons (age range, 15-95 years) from Karksi-Nuia (plus 104 volunteers from the neighborhood) and to native PDC in 497 persons (age range, 50-91 years) from Abja-Paluoja (plus 28 volunteers from that neighborhood). Positive cases were tested with an enzyme inhibition assay., Results: We identified 14 asymptomatic persons with antibodies to native PDC and/or recombinant PDC-E2 from these two population samples. Eight of the 14 were available for follow-up. Three of the 8 developed abnormal liver biochemical test results by the ninth year of follow-up. These persons also had, or developed, during the follow-up, a positive AMA immunofluorescence test, inhibitory antibodies to PDC, and anti-PDC of at least IgG and IgA class. Five of the 8 persons with low levels of anti-PDC, of only one immunoglobulin class reacting with only one PDC preparation, did not show any signs of cholestasis or changes in their immunoreactivity during follow-up., Conclusions: A significant number of asymptomatic patients found to have antibodies to PDC are at high risk of developing primary biliary cirrhosis.