Positive antimitochondrial antibody but normal alkaline phosphatase: Is this primary biliary cirrhosis?

Abstract

Twenty-nine patients with a positive antimitochondrial antibody titer greater than or equal to 1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer greater than or equal to 1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.

Large‐scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis

“…(10) All the 29 patients were previously screened in a workup for another AID. (9) Liver biopsies were performed in the majority of them, and at the screening, 24 patients had histological lesions compatible with or diagnostic of PBC, suggesting that, before the advent of any clinical or biochemical manifestations, those patients did have PBC. Median follow-up was 17.8 years.…”

“…5. Cumulative incidence rates of PBC at 1, 3, and 5 years were 2% (95% CI, 0-7), 7% (95% CI, [2][3][4][5][6][7][8][9][10][11][12][13][14][15], and 16% (95% CI, , respectively. Neither age, sex, AMA titer, PBC-specific ANAs, personal or familial history of AID, or baseline serum levels of bilirubin, ALP, GGT, ALT, or IgM were predictive of PBC development (Table 3).…”

“…(6,7) In such a situation, longitudinal studies seem to indicate AMAs to be inevitably associated with PBC development, but these studies are rather old, all originated from a single UK center and limited area, and involve no more than 29 patients in total. (8)(9)(10) So far, no large, prospective study has been conducted to assess specifically the significance of AMAs in the absence of clinical indications of PBC. The aim of the present study was therefore to evaluate, prospectively and at a large-scale level, the prevalence, clinical characteristics, and outcomes of patients with AMAs, but nonestablished diagnosis of PBC.…”

PBC and AMA?what is the connection?

“…4 A decade later, 76% had developed symptoms of PBC and 83% had cholestatic liver tests. None had progressed to cirrhosis.…”

Editorial: Recurrent primary biliary cirrhosis

“…Most clinicians would accept that such patients have PBC. 6 However, these criteria are not adequate for the diagnosis of recurrent disease because conventional liver tests are not specific and the persistence of autoantibodies may mean no more than that the patient had PBC. The diagnosis of recurrent PBC can be made only on histological criteria.…”