Different Mechanisms May Exist for HBsAg Synthesis and Secretion During Various Phases of Chronic Hepatitis B Virus Infection

Abstract

BACKGROUND The aim of this study was to characterize the expression and secretion of hepatitis B surface-antigen (HBsAg) in the hepatocytes of hepatitis B virus (HBV)-infected patients at different phases of infection; as such, the association of intrahepatic HBsAg expression with virological markers and the histological characteristics were analyzed. MATERIAL AND METHODS 302 chronic HBV infection patients who had not received antiviral therapy were stratified by HBeAg status. The proportion of HBsAg-positive cells was used as an indicator for HBsAg expression level. RESULTS In HBeAg-positive patients, there was a significant correlation between serum HBsAg and serum HBV DNA levels (r=0.569, p<0.001). Intrahepatic HBsAg expression and serum HBsAg level in HBeAg-positive patients were higher than those in HBeAg-negative patients (p=0.002 and p<0.001, respectively). A significant correlation between serum HBsAg level and intrahepatic HBsAg expression was found in HBeAg-negative patients (r=0.377, p<0.001), but not in HBeAg-positive patients (r=0.051, p=0.557). Very interestingly, the correlation between serum HBsAg level and HBsAg expression in hepatocytes gradually increased along with disease progression through the immune-tolerant, immune-clearance, inactive, and recovery phases of HBV infection (r=-0.184, 0.068, 0.492, and 0.575; and p=0,238, 0,722, 0.012, and 0.002, respectively). CONCLUSIONS Different mechanisms may be involved in HBsAg synthesis and secretion in different phases of chronic HBV infection.

Figure 1

HBsAg expression, virological markers and histologic activity of liver disease. The correlation between HBsAg expression in hepatocytes by HBeAg status (A). The correlation between serum HBsAg levels by HBeAg status (B). The correlation between inflammation grade (G), stages of fibrosis (S), and HBsAg expression in hepatocytes by HBeAg status (C: negative, D: positive). The relationship between G and S and serum HBsAg levels by HBeAg status (E: negative, F: positive). The relationship between serum HBV DNA levels and G and S by HBeAg status (G: negative, H: positive).

Figure 2

Correlation between HBsAg titers in hepatocytes and serum, and serum HBV DNA according to HBeAg status. The relationship between serum HBsAg levels and HBsAg expression in hepatocytes by HBeAg status (A: negative, B: positive). The relationship between the serum HBV DNA levels and HBsAg expression in hepatocytes by HBeAg status (C: negative, D: positive). The relationship between serum HBV DNA levels and serum HBsAg levels by HBeAg status (E: negative, F: positive).

Figure 3

The correlation between serum HBsAg levels and HBsAg expression in hepatocytes along the phases of HBV infection. Immune-tolerant phase: HBeAg(+), FS <6, and HBV DNA >10⁶ copies/mL (A). Immune-clearance phase: HBeAg(+), FS > 6, and HBV DNA between 10³ and 10⁶ copies/mL (B). Inactive phase: HBeAg(−), FS >6, and HBV DNA <10³ copies/mL (C). Recovery phase: HBeAg(−), FS >9.4, and HBV DNA >10³ copies/mL (D).

Figure 4

The pathways associated with HBsAg synthesis and secretion in chronic HBV patients.