Correlation of hepatocyte expression of hepatitis B viral antigens with histological activity and viral titer in chronic hepatitis B virus infection: an immunohistochemical study.

BACKGROUND AND AIM The localization of hepatitis B virus (HBV) core antigen to the nucleus or cytoplasm of hepatocytes has biological implications for viral packaging and persistence. This study examined the relationship between the localization of hepatitis B virus antigens, histological activity, and viral titer in patients with chronic HBV infection. METHODS Liver biopsies from 110 patients with chronic HBV infection were studied. Ishak's scoring system was used for the histological analysis. The localization of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and the percentage of hepatocytes stained positive by immunohistochemistry were correlated with viral titer, histological activity, and fibrosis indices using Spearman rank correlation. RESULTS In 88 hepatitis B e-antigen (HBeAg)-positive individuals, the nuclear localization of HBcAg correlated significantly with DNA titer (r = 0.435, P = 0.001) and negatively with fibrosis (r = -0.297, P = 0.005). The cytoplasmic localization correlated significantly with histological activity (r = 0.211, P = 0.049). In 22 HBeAg-negative individuals, the nuclear localization of HBcAg correlated significantly with histological activity (r = 0.625, P = 0.002), DNA titer (r = 0.651, P = 0.009), and fibrosis (r = 0.447, P = 0.042). The cytoplasmic localization correlated significantly with DNA titer (r = 0.524, P = 0.045) and fibrosis (r = 0.528, P = 0.012). There was no correlation of HBsAg expression with DNA titer, histological activity index, or fibrosis in both groups. HBeAg-positive patients presented at a younger age. CONCLUSION In HBeAg-positive individuals, nuclear core antigen correlated with DNA titer, and cytoplasmic localization with histological activity, whereas in HBeAg-negative individuals, nuclear localization correlated with DNA titer, histological activity, and fibrosis, and cytoplasmic localization correlated with DNA titer and fibrosis, but not with histological activity. These observations suggest biological differences between HBeAg-positive and -negative disease.