Role of immunohistochemistry for hepatitis D and hepatitis B virus in hepatitis delta

Liver Int. 2014 Sep;34(8):1207-15. doi: 10.1111/liv.12376. Epub 2013 Dec 5.

Abstract

Background & aims: Immunohistochemical assessment of liver tissue in chronic delta hepatitis (CDH) is underinvestigated. Aim of the study was (i) to assess variables associated with hepatitis D antigen (HDAg), hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) staining in the liver.

Methods: Demographic, biochemical and virologic data collected from the HIDIT 1 study were used. HBsAg, HBcAg and HDAg immunohistochemical (IHC) staining was semiquantitatively assessed.

Results: Hepatitis D antigen immunohistochemical staining displayed positive correlations with age and alanine aminotransferase (ALT) and negative correlations with serum HBsAg (P = 0.01 for all). HBsAg IHC displayed a negative correlation with gamma glutamyl transferase and positive correlations with serum HBV DNA, serum HBsAg levels and HBeAg serology (P < 0.001, P = 0.02 and P = 0.007 respectively). HBcAg staining was mainly nuclear and displayed negative correlations with serum HBsAg and histologic activity (P = 0.002 and P = 0.02 respectively). Pegylated IFN based treatment led to a decline of all IHC markers, however, these markers had no impact on treatment outcome.

Conclusions: These data suggest an association of liver injury with HDAg expression in CDH whereas the negative correlation between HBcAg expression and liver injury and the overall nuclear localization of HBcAg suggest that HBcAg does not contribute to liver injury in CDH. HDV cases with high level of HBV replication, high serum HBsAg levels, HBeAg positivity, that are probably in the earlier stages of disease (low gamma-glutamyl transferase), had a more intense HBsAg staining profile. Overall, the data enforce the importance of HDAg and HBsAg in different phases of CDH infection.

Keywords: Chronic Delta Hepatitis; Delta Antigen; HBcAg; HBsAg; Immunohistochemistry; Quantitative Surface Antigen.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alanine Transaminase / blood
  • Biomarkers / metabolism*
  • Female
  • Hepatitis B Core Antigens / metabolism*
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis D, Chronic / virology*
  • Hepatitis delta Antigens / metabolism*
  • Humans
  • Immunohistochemistry / methods*
  • Liver / metabolism*
  • Liver / virology
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Statistics, Nonparametric
  • gamma-Glutamyltransferase / blood

Substances

  • Biomarkers
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis delta Antigens
  • gamma-Glutamyltransferase
  • Alanine Transaminase

Associated data

  • ISRCTN/ISRCTN83587695