Natural history of early primary biliary cirrhosis

Background In 1986, we reported a group of 29 patients who were positive in serum for antimitochondrial antibody (AMA), the disease-specific marker for primary biliary cirrhosis (PBC), but who had normal liver function test results and no symptoms of liver disease. However, liver histology was diagnostic or compatible with PBC in 24 patients and normal in only two. The aims of this 10-year follow-up study were to establish whether patients with AMA have very early PBC, to assess the outlook for such patients, and to follow the progression of the disease. Methods All patients were assessed every year at our PBC clinic: records were reviewed, cause of death verified when applicable, and current clinical and biochemical data collected, including repeat liver histology as indicated. Serum samples from the original study were located. Original and follow-up serum samples were tested by ELISA for E2 components of pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex. Findings Five patients died during follow-up; no deaths were attributable to liver disease. Median follow-up of patients who survived was 17.8 years (range 11.0-23.9) from first-detected AMA to the last follow-up review. Overall, 22 (76%) developed symptoms of PBC and 24 (83%) had liver function tests persistently showing cholestasis. Repeat liver biopsy samples were obtained from ten patients; among these patients PBC progressed from Scheuer grade 1 to grade 2 in two and from grade 1 to grade 3 in two. No patient developed clinically apparent cirrhosis. ELISA of baseline serum samples from 27 patients was positive in 21, all of whom had original liver histology compatible with or diagnostic of PBC. Of the six patients who tested negative, only one had an original liver biopsy sample that was compatible with PBC. Interpretation This study confirms that before the advent of any clinical or biomedical indications, individuals positive for AMA do have PBC. This finding extends the natural history of PBC back in some cases for many years. What determines the eventual progression to biochemically and clinically apparent disease is not yet understood. During our study no patient developed clinically apparent portal hypertension or cirrhosis. Thus, although the finding of a solitary persistently raised AMA is confirmation of a diagnosis of PBC, patients with AMA but no other signs or symptoms of PBC seem to have slow progression of the disease.