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

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 ( HDA g), hepatitis B surface antigen ( HB sAg) and hepatitis B core antigen ( HB cAg) staining in the liver. Methods Demographic, biochemical and virologic data collected from the HIDIT 1 study were used. HB sAg, HB cAg and HDA g 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 HB sAg ( P = 0.01 for all). HB sAg IHC displayed a negative correlation with gamma glutamyl transferase and positive correlations with serum HBV DNA , serum HB sAg levels and HB eAg serology ( P < 0.001, P = 0.02 and P = 0.007 respectively). HB cAg staining was mainly nuclear and displayed negative correlations with serum HB sAg 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 HDA g expression in CDH whereas the negative correlation between HB cAg expression and liver injury and the overall nuclear localization of HB cAg suggest that HB cAg does not contribute to liver injury in CDH . HDV cases with high level of HBV replication, high serum HB sAg levels, HB eAg positivity, that are probably in the earlier stages of disease (low gamma‐glutamyl transferase), had a more intense HB sAg staining profile. Overall, the data enforce the importance of HDA g and HB sAg in different phases of CDH infection.