Impact of precore and core promoter mutations on hepatic histology in patients with chronic hepatitis B

Aliment Pharmacol Ther. 2005 Aug 15;22(4):301-7. doi: 10.1111/j.1365-2036.2005.02563.x.

Abstract

Background: The details of liver histology of patients with precore and core promoter mutations are still not clear.

Aim: To determine the role of precore and core promoter mutations in liver histology in Chinese patients with chronic hepatitis B.

Patients and methods: Intrahepatic hepatitis B virus DNA (by COBAS Amplicor hepatitis B virus Monitor test) and precore and core promoter mutations (by a line probe assay) were measured in 54 chronic hepatitis B patients. Expression of hepatitis B core antigen, hepatitis B e antigen and hepatitis B surface antigen was determined by immunohistological staining. Histological activity index was scored according to Knodell's criteria.

Results: Compared with patients without core promoter mutations, patients with core promoter mutations had more severe intrahepatic inflammation and fibrosis, and more cytoplasmic expression of hepatitis B core antigen (P = 0.028). No such differences were found in patients with and without precore mutations. Logistic regression showed that core promoter mutations were independently associated with cytoplasmic expression of hepatitis B core antigen (P = 0.026). Intrahepatic hepatitis B virus DNA levels correlated with serum hepatitis B virus DNA levels (r = 0.71, P < 0.001) and the percentage of hepatitis B core antigen-positive hepatocytes (r = 0.37, P = 0.047), but had no correlation with serum alanine aminotransferase levels nor the degree of inflammation and fibrosis.

Conclusions: Patients with core promoter mutations had more severe inflammation and fibrosis, and more frequent cytoplasmic expression of hepatitis B core antigen. This suggested that core promoter mutations might cause more serious liver disease.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • DNA, Viral / genetics
  • Female
  • Hepatitis B Core Antigens / metabolism
  • Hepatitis B e Antigens / metabolism
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis B, Chronic / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Promoter Regions, Genetic / genetics

Substances

  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B e Antigens