Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis.
OBJECTIVE
To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) with AIH features.


METHODS
Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined. The activity of periportal and lobular inflammation was scored 0 (none or minimal activity) to 4 (severe), and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3. The infiltration of mononuclear cells positive for CD20, CD38, CD3, CD4, and CD8 and positive for immunoglobulins (IgG, IgM, and IgA) at the periportal areas (interface hepatitis) and in the hepatic lobules (lobular hepatitis) were semiquantitatively scored in immunostained liver sections (score 0-6). Serum aspartate aminotransferase (AST), immunoglobulins, and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.


RESULTS
Lobular hepatitis, hepatitic rosette formation, and emperipolesis were more extensive and frequent in AIH than in PBC. CD3+, CD4+, and CD8+ cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC. The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC, but to a lesser degree in AIH. CD20+ cells were mainly found in the portal tracts and, occasionally, at the interface in both diseases. Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration, specifically CD38+ cells in PBC. No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH. While most AIH cases were IgG-predominant at the interface, PBC cases were divided into IgM-predominant, IgM/IgG-equal, and IgG-predominant types, with the latter sharing several features with AIH.


CONCLUSIONS
These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Mio
M
Kobayashi
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Yuko
Y
Kakuda
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Kenichi
K
Harada
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Yasunori
Y
Sato
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Motoko
M
Sasaki
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Hiroko
H
Ikeda
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Mitsuhiro
M
Terada
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Munenori
M
Mukai
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Shuichi
S
Kaneko
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Yasuni
Y
Nakanuma
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D018951:Antigens, CD20 / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001707:Biopsy, Needle; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D006505:Hepatitis / Q000175:diagnosis*; D019693:Hepatitis, Autoimmune / Q000175:diagnosis*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged
D018951:Antigens, CD20; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D001219:Aspartate Aminotransferases; D051997:ADP-ribosyl Cyclase 1
Autoimmune hepatitis; Interface hepatitis; Lobular hepatitis; Plasma cell subclass; Primary biliary cirrhosis