Intrahepatic expression of pre-S proteins of hepatitis B virus and its possible relation to liver cell necrosis.

To assess the significance of intrahepatic expression of pre-S1 and S2 proteins of hepatitis B virus (HBV) in patients with HBV infection, an indirect immunoperoxidase technique employed monoclonal antibodies to pre-S proteins was used to detect pre-S1 and -S2 proteins in 80 liver specimens. The frequency of pre-S1 and -S2 proteins was 61.3% and 51.3%, respectively, and the co-expression of pre-S and HBsAg occurred in most specimens. The preferential expression of pre-S1 and -S2 in HBcAg-positive specimens suggests that pre-S proteins are associated with HBV replication. Membranous expression of both pre-S1 and -S2 is associated with inflammatory activity and liver cell necrosis. Furthermore, our results show that T cells, not NK or B cells, were the predominantly infiltrating cells in necrotic foci with pre-S expression. Almost all of these T cells may express HLA-DR antigen simultaneously; therefore, they are activated. In conjunction with these data, we conclude that, as the essential components of HBV envelope proteins, pre-S proteins may play an important role in resulting in liver cell necrosis.