Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic mice model.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) overlapping with chronic hepatitis B virus (HBV) infection is undergoing a rapid increase in China. Therefore, the establishment and character of an animal model with both NAFLD and chronic HBV infection has become an urgent task. METHODS: Mice with chronic HBV genotype B infection were established with a microinjection of oocytes. Transgenic and nontransgenic mice were then randomized into groups of NAFLD + HBV, HBV, NAFLD, and control and were treated with high-fat diets or common forage. At 8, 16, and 24 weeks, characteristics of NAFLD were evaluated by physical indices, liver function tests, glycolipid metabolism, and histopathological scoring. Viral dynamics were also analyzed by HBV-DNA and HBV-related antigens. RESULTS: Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were expressed, and HBV-DNA was replicated in HBV transgenic mice at different stages in the serum and liver. Hepatic steatosis was only induced after exposure of the mice to high-fat diets, and no obvious pathological changes occurred in the HBV group from 8 to 24 weeks. Compared to mice with HBV alone, significant reductions in serum levels of HBV-DNA, HBsAg and HBeAg occurred in the NAFLD + HBV group after 24 weeks (all P < 0.05). Nevertheless, the NAFLD and NAFLD + HBV groups shared comparable physical and metabolic disorders and similar steatotic, inflammatory and fibrotic characteristics in the liver. CONCLUSION: High-fat diets and transgenic operations on the HBV genotype B induced a rodent model of NAFLD overlapping with chronic HBV infection, and this model reduces the HBV viral factors but not the metabolic and histologic features.

Non-cytolytic antigen clearance in DNA-vaccinated mice with electroporation.

AIM: To explore the potential of electroporation (EP)-mediated hepatitis B virus (HBV) DNA vaccination for the treatment of chronic HBV infection. METHODS: BALB/c mice were vaccinated with HBV DNA vaccine encoding for the HBV preS(2)-S antigen, combined with or without EP. HBV surface antigen expression plasmid was administered into mice liver via a hydrodynamic injection to mimic HBV infection. The clearance of antigen in the serum and liver was detected by ELISA assay and immunohistochemical staining. The histopathology of the liver tissues was examined by HE staining and serum alanine aminotransferase assay. RESULTS: The immunogenicity of HBV DNA vaccine encoding for the HBV preS(2)- S antigen can be improved by EP-mediated vaccine delivery. The elicited immune responses can indeed reduce the expression of HBV surface antigen (HBsAg) in hepatocytes of the mouse model that was transfected to express HBsAg using the hydrodynamic injection method. The antigen clearance process did not cause significant toxicity to liver tissue, suggesting a non-cytolytic mechanism. CONCLUSION: The EP-aided DNA vaccination may have potential in mediating viral clearance in chronic hepatitis B patients.