Qualitative and quantitative differences between bile ducts in chronic hepatitis and in primary biliary cirrhosis

Aim—Lymphocytic infiltration in the portal triads usually conceals the detection—in haematoxylin and eosin (H&E) stained sections—of bile ducts in two liver diseases: chronic hepatitis and primary biliary cirrhosis. The aim was to assess the number and the characteristics of the bile ducts in those diseases with the aid of an antibody to cytokeratin 7 (CK7) Methods—Consecutive sections from 99 liver biopsies were stained with H&E and anti-CK7. Results—In H&E sections the total number of central bile ducts in the triads was 52 in primary biliary cirrhosis (n = 37), 69 in chronic hepatitis (n = 43), and 30 in miscellaneous cases (n = 19). Using anti-CK7, the number of central bile ducts was 276 in primary biliary cirrhosis, 348 in chronic hepatitis, and 96 in miscellaneous cases. Central bile ducts with lumen were found in 93.0% of chronic hepatitis cases and in 89.5% of the miscellaneous cases, but in only 13.5% of the primary biliary cirrhosis cases. Peripheral bile ducts in groups of ≥ 4/triad were found in all cases of chronic hepatitis (100%) and in 75.7% primary biliary cirrhosis cases, but only in 10.5% of the miscellaneous cases. In 21.6% of primary biliary cirrhosis cases, no bile ducts (central and/or peripheral) were present. Conclusions—Anti-CK7 detects bile ducts in the triads that are concealed by chronic inflammatory cells. Central and peripheral bile ducts in groups of ≥ 4 were significantly more common in primary biliary cirrhosis and chronic hepatitis than in other liver diseases. The lack of lumen in central bile ducts, as well as the absence of central and/or peripheral bile ducts in CK7 stained liver sections, seem to be valuable additional parameters in the differential diagnosis between primary biliary cirrhosis and chronic hepatitis. Key Words: bile ducts • cytokeratin 7 • primary biliary cirrhosi

Autoantigens in primary biliary cirrhosis

The automimmune liver disease primary biliary cirrhosis (PBC) is characterised by serum autoantibodies directed at mitochondrial and nuclear antigens (seen in most patients and a subset of patients, respectively). The antimitochondrial antibodies (AMA) characteristic of PBC are directed at members of the 2-oxoacid dehydrogenase components of multienzyme complexes; in particular, the E2 and E3 binding protein (E3BP) components of the pyruvate dehydrogenase complex (PDC). The presence of autoantibodies reactive with PDC-E2 and/or E3BP is strongly predictive of the presence of PBC. Therefore, the detection of these antibodies plays a very important role in the diagnosis of PBC. Originally demonstrated using immunofluorescence approaches, AMA can now be detected by the use of commercially available enzyme linked immunosorbent assays (ELISAs). Although the ELISA based approaches have advantages in terms of laboratory practicality, they are slightly less sensitive for the diagnosis of PBC than immunofluorescence (occasional patients with PBC show reactivity with PDC related antigens not present in the antigen preparations available for use with ELISA). Therefore, immunofluorescence should continue to be available as a complementary diagnostic test for use in occasional patients. In a subset of patients with PBC, autoantibodies are directed at increasingly well characterised nuclear antigens. Antinuclear antibody (ANA) positive patients are typically AMA negative. There are no significant differences in disease phenotype between AMA positive and AMA negative groups. At present, the clinical detection of ANA is mostly by Hep2 immunofluorescence, although ELISA kits for individual nuclear antigens are increasingly becoming available. Key Words: liver cirrhosis • biliary • autoimmunity • autoantibod