Histopathological analysis of chronic hepatitis B virus (HBV) infection in relation to HBV replication.

The interrelationship among expression patterns of hepatitis B surface and core antigens (HBsAg and HBcAg) in the liver, hepatitis B virus (HBV) DNA in sera, HBeAg/anti-HBe status and histological features was examined in 189 liver specimens and 106 sera from Japanese patients with chronic HBV infection, utilizing immunoperoxidase methods and a spot hybridization technique. HBsAg and HBcAg were distributed uniformly among the lobules in 8 viral carriers with "normal" liver (NVC) and 30 patients with persistent hepatitis (PB) seropositive for HBcAg. This uniform staining pattern was quite distinct from the non-uniform and irregular patterns in 137 patients with chronic active hepatitis (CAH) associated with or not associated with cirrhosis. HBcAg was often found to be stained strongly in the cytoplasm as well as in the nucleus of hepatocytes in HBeAg-positive CAH, in contrast to NVC/PH, in which cytoplasmic HBcAg was very weak. Serum HBV DNA was detected in all 22 cases with HBeAg-positive NVC/PH, 41 of 46 (89.1%) cases with HBeAg-positive CAH, 6 of 23 (26.1%) casew with anti-HBe-positive CAH and none of 3 cases with anti-HBe-positive NVC/PH. The level of serum HBV DNA and staining of HBcAg were in decreasing order in these groups. While the presence of serum HBV DNA and HBcAg staining was always associated with HBeAg seropositivity in NVC/PH, this was not always found in CAH. Moreover, necroinflammatory activity in the liver did not always parallel viral replication in CAH. These findings seem to confirm that NVC/PH and CAH have different biologic processes; viral replication is always concordant in the former, but is sometimes discordant in the latter with HBeAg/anti-HBe status. The immunologic response of the host seems to suppress and distort replication of the virus to a varying degree among patients and areas of the same liver in CAH differently to that in NVC/PH. The different life cycle of the virus, including integration of viral DNA into the cellular genome, may subsequently result in discordant states of various virus markers in CAH.