Original Article
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World J Gastroenterol. Apr 7, 2014; 20(13): 3597-3608
Published online Apr 7, 2014. doi: 10.3748/wjg.v20.i13.3597
Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis
Mio Kobayashi, Yuko Kakuda, Kenichi Harada, Yasunori Sato, Motoko Sasaki, Hiroko Ikeda, Mitsuhiro Terada, Munenori Mukai, Shuichi Kaneko, Yasuni Nakanuma
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 Ikeda, Division of Pathology, Kanazawa University Hospital, Kanazawa 920-8641, Japan
Mitsuhiro Terada, Department of Gastroenterology, Kouseiren Takaoka Hospital, Takaoka 933-8555, Japan
Munenori Mukai, Department of Pathology, Kouseiren Takaoka Hospital, Takaoka 933-8555, Japan
Shuichi Kaneko, Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
Author contributions: Kobayashi M performed the majority of experiments and wrote the manuscript; Kakuda Y analyzed the data; Harada K, Sato Y and Sasaki M contributed to the design of the study; Ikeda H, Terada M, Mukai M and Kaneko S provided the experimental materials; Nakanuma Y organized the study.
Supported by Primary Biliary Cirrhosis Subdivision of Intractable Hepatobiliary Diseases Study Group of Japan (Chairman, Hirohito Tsubouchi; Department of Human and Environmental Sciences, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan)
Correspondence to: Yasuni Nakanuma, MD, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Takaramachi 13-1, Kanazawa 920-8640, Japan. nakanuma@staff.kanazawa-u.ac.jp
Telephone: +81-76-2652197 Fax: +81-76-2344229
Received: May 28, 2013
Revised: July 26, 2013
Accepted: August 17, 2013
Published online: April 7, 2014
Abstract

AIM: 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.

CONCLUSION: These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.

Keywords: Primary biliary cirrhosis, Autoimmune hepatitis, Interface hepatitis, Lobular hepatitis, Plasma cell subclass

Core tip: Primary biliary cirrhosis (PBC) can sometimes present with features of autoimmune hepatitis (AIH). Therefore, the clinicopathological features and immunophenotypes of infiltrated mononuclear cells of AIH and PBC with AIH features were examined. Lobular hepatitis, hepatitic rosette formation, and emperipolesis were more frequent in AIH than PBC. The degree of mononuclear cell infiltration correlated well with hepatitis. Furthermore, elevation of aspartate aminotransferase levels correlated well with necroinflammation and infiltration of mononuclear cells in PBC, which tended to be IgM-predominant. These results suggest that hepatocellular injuries in AIH and PBC may not be identical.