Associations of Expressions of HBcAg and HBsAg with the Histologic Activity of Liver Disease and Viral Replication

Abstract

Background/Aims: Subcellular localization of hepatitis B virus (HBV) core antigen (HBcAg) and HBV surface antigen (HBsAg) is known to be related to the activity of liver disease and the level of HBV replication. The aim of this study was to determine the correlation between histologic activity, viral replication, and the intracellular distributions of HBcAg and HBsAg. Methods: We enrolled 670 patients with chronic hepatitis B who underwent liver biopsy at Bundang CHA hospital between 1997 to 2007. The data from medical records were reviewed retrospectively. Results: The stage of fibrosis was higher (3.31±1.34 vs. 2.43±1.39, mean±SD, p＜0.01) and the grade of necroinflammatory activity was higher (9.39±3.11 vs. 6.13±3.40, p＜0.001) for the cytoplasmic expression of HBcAg (cHBcAg) than for the nuclear expression of HBcAg (nHBcAg). The serum HBV DNA level was 677.30±983.14 pg/mL in cHBcAg, 1274.46±1417.28 pg/mL in nHBcAg, 1121.01±1121.0 pg/mL in c-nHBcAg, and 229.47±678.92 pg/mL in negative (p＜0.001). HBeAg was seropositive in 74.7% of patients with cHBcAg, 90.6% in those with nHBcAg, 90.3% in those with n-cHBcAg, and 55.6% in those with negative (p＜0.001). The histologic stage and grade of hepatitis were not significantly correlated with the subcellular localization of intrahepatic HBsAg (p＞0.05). Conclusions: These observations suggest that the histologic activity of hepatitis is higher and viral replication is lower in cHBcAg positive patients than in those with nHBcAg. (Gut and Liver 2008;2:166-173)

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

“…Among HBeAgnegative patients, only one had positive but rare distribution intrahepatic HBcAg. These results are consistent with previous reports that higher level of viral replication (or serum HBV DNA) is associated with diffuse dis tribution and mixed cytoplasmic/nuclear pattern of HBcAg [7,8,11,13,18,24,30] . In contrast to HBcAg, all patients had positive intrahepatic HBsAg regardless of their HBeAg status, and its distribution did not correlate with HBV DNA levels.…”

Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients

“…Based on these results, we expected good delineation of the evolution of CHB in HBeAg-positive patients by the HBcAg and HBsAg expression pattern. At the initial phase, the hepatocyte HBcAg expression shifts from nucleus to cytoplasm with advancing age and intensifying hepatic inflammation and fibrosis, as suggested in the present as well as a previous study 9. Then, HBcAg expression ultimately disappears in association with a significant reduction of viral load, followed by the alteration of HBsAg expression pattern from non-submembranous (diffuse and globular) to submembranous type, in conjunction with a further increase in age and disease progression.…”

“…The intrahepatic expression of HBcAg is reportedly related to the presence of serum HBeAg and HBV replication, and its expression patterns have also been correlated with the degree of hepatic inflammation 6–9. Furthermore, the presence of hepatocytes with HBsAg membranous staining was positively correlated with serum HBV DNA levels, suggesting its role as a marker of active viral replication 10,11.…”

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

“…The CD4 + lymphocyte is known to be a very specific immune reaction to HBcAg, and the CD8 + lymphocyte plays an important role in viral clearance 12,13. HBcAg expression pattern in hepatocytes had been found to be related to the activity of liver disease, hepatocyte proliferation, and HBV DNA level 14. In previous studies, the cytoplasmic type was seen in patients with active hepatitis and hepatocyte regeneration 3,4.…”