Diverse virological, histopathological and prognostic implications of seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection.

The evolutions of serum hepatitis B virus (HBV)-DNA, liver histology and intrahepatic expressions of HBV antigens were longitudinally investigated in 24 serum HBeAg+/HBV-DNA+ chronic hepatitis B patients who subsequently seroconverted to anti-HBe. After HBeAg conversion, serum HBV-DNA still persisted in 10 patients, and liver HBcAg in 7 of them. Of the 24 patients, 3 subgroups with diverse prognoses were identified. Ten patients progressed from chronic active hepatitis to cirrhosis, and in 7 of them HBV-DNA and/or HBcAg persisted. Eight patients with undetectable HBV-DNA and HBcAg recovered. In the remaining 6 patients, chronic liver diseases persisted; in 3 of them, HBV-DNA and in one HBcAg. These findings indicate that continued viral replication is present in a significant number of patients after HBeAg seroconversion in Taiwan, and is responsible for disease progression. In addition to HBcAg and HBV-DNA, the severity of underlying liver histology, when HBeAg seroconversion occurred, was critical for the outcome of the disease. Another remarkable finding was that clusters of ground-glass hepatocytes, well correlated with the marginal expression of HBsAg, were demonstrated in 14 of 16 biopsies with serum anti-HBe+/HBV-DNA-, but found in only 4 of 44 biopsies with positive serum HBV-DNA, indicating a strong association of the expressions of liver histology and hepatocyte HBsAg with the status of viral replication.