Value of Autoantibody Analysis in the Differential Diagnosis of Chronic Cholestatic Liver Disease

BACKGROUND & AIMS: It is challenging to diagnose patients with chronic cholestatic liver diseases when all the classic criteria are not fulfilled. We evaluated the performance of the recently developed MIT3-based enzyme-linked immunosorbent assay (ELISA), which detects antimitochondrial autoantibodies (AMAs), together with ELISAs for other autoimmune liver disease-related antibodies in patients with chronic cholestatic liver disease. METHODS: Sera from 281 patients with chronic cholestatic conditions, including primary biliary cirrhosis (PBC), primary sclerosing cholangitis, AMA-positive autoimmune hepatitis, and "undetermined cholangiopathy" were tested for the following PBC-associated autoantibodies: anti-gp210, anti-sp100, conventional anti-M2, anti-M2 (MIT3) IgG, anti-M2 (MIT3) IgA, as well as anti-centromere, anti-soluble liver antigen, and anti-chromatin. RESULTS: Of 57 patients with PBC who were AMA-negative by conventional M2 ELISA, 14 were found to be AMA-positive by the MIT3-IgG assay. Furthermore, on the basis of the data from 3 tests (MIT3-IgG, gp210, and sp100), PBC was confirmed in 20 of 57 (35%) patients diagnosed with AMA-negative PBC. We confirmed that sp100 and gp210 antibodies were detected only in patients with PBC and AMA-positive autoimmune hepatitis, whereas gp210 was detected more frequently in patients known to have had a poor outcome. Of the 11 patients with an undetermined cholangiopathy, 3 (27%) tested positive for PBC with the MIT3-IgG assay. In contrast to previous findings, anti-centromere antibodies were not found to be associated with poor outcome in PBC. CONCLUSIONS: ELISAs for AMAs and antinuclear antibodies are useful in diagnosis and prognosis of patients with features of PBC who lack conventional AMA and in patients with a cholangiopathy of undetermined etiology.