Hepatic Expression of Intercellular Adhesion Molecule–1 (Icam–1) in Viral Hepatitis B

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Abstract
The in situ distribution patterns of intercellular adhesion molecule–1 and human leukocyte antigen–DR antigens were studied in serial sections of 61 liver biopsy specimens from patients with hepatitis B virus infection using immunohistochemical techniques. In addition, the topographical relationship between the display of HBcAg on one hand and the expression of intercellular adhesion molecule–1 by hepatocytes on the other was analyzed with a double–staining immunohistochemical procedure in 14 selected liver biopsy samples showing chronic persistent or chronic active hepatitis and signs of active hepatitis B virus replication as reflected by the presence of variable amounts of HBcAg in a nuclear or cytoplasmic pattern of immunoreactivity. Coexpression of intercellular adhesion molecule–1 and human leukocyte antigen–DR antigens by hepatocytes correlated positively with the site and extent of the inflammatory infiltrate, which was composed of lymphocytes expressing lymphocyte function-associated antigen–1. In healthy HBsAg–positive carriers without inflammatory liver disease, no intercellular adhesion molecule–1 or human leukocyte antigen–DR expression was found on hepatocytes; in acute hepatitis, intercellular adhesion molecule–1 and human leukocyte antigen–DR were strongly expressed throughout the liver parenchyma on liver cell membranes and on sinusoidal lining cells. In chronic persistent and chronic active hepatitis and in active cirrhosis, intercellular adhesion molecule–1 and human leukocyte antigen–DR showed membranous positivity on focal clusters of hepatocytes in areas of periportal or intraacinar inflammation. Double–staining for HBcAg and intercellular adhesion molecule–1 revealed variable numbers of HBcAg–positive hepatocytes expressing intercellular adhesion molecule–1 on their cell membranes; these cells may represent the “cytotoxic” model, in which cell–cell interactions between lymphocyte function-associated antigen–1-positive lymphocytes and hepatitis B virus-infected hepatocytes are facilitated. Furthermore, intercellular adhesion molecule–1-positive hepatocytes lacking HBcAg were found in areas of inflammation, indicating that the virus itself does not directly trigger intercellular adhesion molecule–1 expression. These intercellular adhesion molecule–1-positive, HBcAg–negative liver cells might “guide” lymphocytes through the parenchyma toward virally infected target cells. Finally, in many cases, variable numbers of HBcAg–positive liver cells lacked membranous intercellular adhesion molecule–1 expression; these cells may represent the “tolerogenic” model, in which incomplete clearance of virally infected hepatocytes adds to the chronic nature of hepatitis B virus infection. (Hepatology 1990;12:148-154).