Change of hepatitis B virus DNA distribution associated with the progression of chronic hepatitis.

Hepatitis B virus (HBV) DNA was detected by in situ hybridization in 53 out of 74 liver specimens from patients with chronic HBV infection. The distribution of HBV DNA was classified into three patterns: diffuse (HBV DNA distributed diffusely, within the section of specimen), lobular (HBV DNA was present in 1/3-2/3 of the section) and spotty. All three specimens from asymptomatic HBV carriers showed the diffuse pattern. In the advanced stage of liver disease (chronic active hepatitis with severe activity and liver cirrhosis), a decreased number of specimens showed the diffuse pattern, whereas the number of specimens with the lobular pattern increased. From these data, we conclude that HBV may replicate diffusely in the liver in the early stage of chronic liver disease, and the site of HBV replication becomes localized in the advanced stage of the disease. The main target cells of immunocytes may be hepatocytes undergoing HBV replication, because HVB DNA was frequently detected in areas of focal, piecemeal and bridging hepatic necrosis.