title: Role of immunohistochemistry for hepatitis D and hepatitis B virus in hepatitis delta.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Kabaçam
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Berna
authors.initials: B
authors.lastname: Savaş
authors.forename: Onur
authors.initials: O
authors.lastname: Keskin
authors.forename: George
authors.initials: G
authors.lastname: Dalekos
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idilman
authors.forename: Andreas
authors.initials: A
authors.lastname: Erhardt
authors.forename: Kendal
authors.initials: K
authors.lastname: Yalçın
authors.forename: Mithat A
authors.initials: MA
authors.lastname: Bozdayi
authors.forename: Hakan
authors.initials: H
authors.lastname: Bozkaya
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.forename: Hans
authors.initials: H
authors.lastname: Dienes
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydın
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D019701:Hepatitis D, Chronic / Q000821:virology*; D035923:Hepatitis delta Antigens / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008099:Liver / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D035923:Hepatitis delta Antigens; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase
keywords: Chronic Delta Hepatitis; Delta Antigen; HBcAg; HBsAg; Immunohistochemistry; Quantitative Surface Antigen