The role of large (pre-S1) and middle (pre-S2)
proteins of
HBsAg in hepatitis B virus (HBV)
infection is not fully known. Therefore, we studied the expression of
pre-S proteins in the liver and serum of 26 patients with chronic HBV
infection, using immunoperoxidase staining and
enzyme immunoassay. Pre-S1 and pre-S2
proteins were detected in a large number of patients in both liver and serum, irrespective of the disease activity. Serial sections showed that most cells positive for
HBsAg were also positive for
pre-S proteins. The localization of pre-S2 and
HBsAg was similar, with cytoplasmic and membranous stainings of hepatocytes, whereas pre-S1 was expressed exclusively in cytoplasm. Serum levels of
HBsAg, pre-S1, and pre-S2 of
DNA polymerase-positive cases were significantly higher than those of
DNA polymerase-negative cases. Membranous display of pre-S2 on hepatocytes was observed more often in
DNA polymerase-positive patients, and their serum pre-S2 levels were significantly higher than those without it. The predominant localization of cytoplasmic
HBcAg usually was associated with active, ongoing
hepatitis. Its expression and
DNA polymerase activity were significantly correlated. These results indicate that
pre-S proteins in serum and the membranous display of pre-S2 on hepatocytes of patients with chronic HBV
infection refect active viral replication, but their expression does not correlate with disease activity.