The correlation of hepatocyte nuclear factor 4 alpha and 3 beta with hepatitis B virus replication in the liver of chronic hepatitis B patients

Hepatocyte nuclear factors 4 alpha (HNF4 alpha) and 3 beta (HNF3 beta) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV). Using cell culture and animal models, we showed that HNF4 alpha supports HBV replication in nonhepatic cells and HNF3 beta inhibits HBV replication. However, the expression of HNF4 alpha and HNF3 beta in the liver tissue of chronic HBV-infected patients and the relationship between the levels of HNF4 alpha and HNF3 beta and HBV replication are unclear. In this study, liver biopsy specimens from 86 chronic HBV-infected patients were collected. The expression levels of HNF4 alpha, HNF3 beta, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were detected by an immunohistochemical technique and the level of HBV DNA was checked by in situ hybridization with serial sections from liver biopsy tissue samples. We show here that samples with higher levels of HNF4 alpha expression also have higher levels of HBsAg, HBcAg and HBV DNA. In contrast, in samples with higher levels of HNF3 beta expression, levels of HBsAg, HBcAg and HBV DNA were lower. There was a positive correlation between HNF4 alpha expression and HBV replication, and a negative correlation between HNF3 beta expression and HBV replication, in the liver of chronic HBV-infected patients. This suggests that HNF4 alpha and HNF3 beta likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4 alpha and HNF3 beta in the liver.