Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis

Abstract

Reports from North America and Northern Europe have suggested that antimitochondrial antibody (AMA) negative primary biliary cirrhosis (PBC) is a distinct chronic cholestatic liver disease with high prevalence of serum non‐organ‐specific autoantibodies other than AMA. To evaluate if such a peculiar serum immunoreactivity is associated with clinically relevant characteristics, we reviewed our experience with 297 Italian patients who have had a clinical and histological diagnosis of PBC and were regularly followed‐up at our Center from June 1974 to June 1994. AMA‐negative and AMA‐positive patients were compared in terms of biochemical and clinical features, and clinical outcome of the disease. At presentation, 30 of 297 patients (10%) tested negative for AMA by indirect immunofluorescence. Six of them tested positive for antimitochondrial M2 antibodies (AMA‐M2) by immunoblotting analysis, therefore, diagnosis of AMA‐negative PBC was made in 24 patients (8%). At the initial visit, AMA‐negative and AMA‐positive patients were similar in terms of biochemical and clinical features. Antinuclear and anti‐smooth‐muscle antibodies (ANA and ASMA) were more frequently positive in the AMA‐negative patients (71% vs. 31%, and 37% vs. 9%; both P = .0002). Incidence of complications of cirrhosis and development of liver failure resulting in death or referral for liver transplantation did not differ significantly between the two populations. In conclusion, data from this historical cohort study suggest that the distinct serological features of AMA‐negative PBC are not associated with substantial differences in the clinical spectrum or course of the disease.

Primary biliary cirrhosis once rare, now common in the United Kingdom?

“…In respect to the 23 patients who were AMA negative, but had abnormal LFTs and diagnostic liver histology, we feel that we are justified to include them because AMA-negative PBC is widely regarded as part of the spectrum of PBC. [11][12][13] Because of our case finding methods we may have underestimated the prevalence and proportion of AMA-negative PBC in our population.…”

PBC and AMA?what is the connection?

“…8,9 Some patients in whom AMA are not detectable by conventional indirect immunofluorescence, may nevertheless be AMA positive when assessed by immunoblotting. 10,11 Furthermore, the use of cloned mitochondrial antigens such as triple hybrid recombinant molecule (r-MIT3) which contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2 12 may identify AMA in the sera of patients previously thought to be AMA negative. Some patients labeled as having AMA-negative PBC, or ''autoimmune cholangitis,'' 6 may therefore be AMA positive rather than truly AMA negative.…”

Primary Biliary Cirrhosis Associated with Painless Thyroiditis.

“…On the other hand, some forms ofAMA-negative PBCare believed to be a distinct clinical entity designated as autoimmune cholangitis (5-7). However, it is suggested that AMA-positive and AMA-negativePBCshare a similar clinical spectrum and outcome (8,9). The present paper describes a patient with AMA-negative PBCassociated with hyperthyroidism caused by painless thyroiditis.…”

“…Someauthors have found differential features, such as piecemeal necrosis, positive ASMA, higher serum aminotransferase levels, lower serum IgMlevels, and a benefical effect of prednisone and azathioprine in patients with autoimmunecholangitis (26). On the other hand, a similar clinical spectrum and a similar outcomeof the disease have been reported in AMA-negative and AMA-positive PBC, although different patterns of immunoreactivity are present in the two conditions (8,9). In the case presented here, normal serum aminotransferase levels and higher serum IgM levels were noted and serum ALPand y-GTP levels were improved with ursodeoxycholic acid.…”