Immunohistochemical techniques for the demonstration of viral antigens in liver tissue

Liver biopsy specimens from patients positive for serum HBsAg reveal various expression patterns when properly stained by immunohistochemical techniques for the demonstration of HBsAg, HBcAg and HDAg. A negative staining for these three antigens seems to be associated with two conditions, i.e., self-limiting acute lobular hepatitis (ALH) or low amounts of intrahepatic antigens. The discrepancy between serum positivity and tissue negativity for HBsAg can be explained either by sampling error or by the higher sensitivity of the radioimmunoassay as compared with immunohistochemical methods. The use of amplification systems such as the avidin-biotin-peroxidase complex enhances the sensitivity of immunohistochemical peroxidase-antiperoxidase (PAP) techniques and makes it possible to detect very small amounts of both HBsAg and HBcAg in liver cells from paraffin-embedded tissue sections which had been negative with the conventional PAP technique. In cases with a positive staining for viral antigens, two main expression patterns (non-aggressive and aggressive) can be distinguished. The non-aggressive pattern is reflected in the HBcAg-free HBsAg-positive type (HBsAg carrier) or the generalized type of nuclear core (HBcAg carrier), while the aggressive pattern is reflected in the presence of HDAg, the presence of HDAg and HBcAg, the focal type of nuclear core or the cytoplasmic HBcAg. Superinfection of HBsAg carriers or switching from generalized to focal core, with or without cytoplasmic expression of HBcAg, results in transition from non-aggressive to aggressive pattern. The aggressive pattern occurs in association with histological features of chronic active hepatitis (CAH). When it occurs in ALH cases or in milder forms of chronic hepatitis, an evolution into CAH has to be expected. Features of severe CAH, eventually with cirrhosis, are found in association with two new expression patterns: the cytoplasmic core and the simultaneous presence of HBcAg and HDAg. When features of CAH are observed in liver tissue specimens with HBcAg-free HBsAg-positive type, the liver disease may be due to viral superinfection or to non-viral etiology, e.g., alpha 1-antitrypsin deficiency.