title: Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma.
abstract: OBJECTIVE
  To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma.
  
  
  METHODS
  A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system.
  
  
  RESULTS
  Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to "rare" distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively.
  
  
  CONCLUSIONS
  Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Parham
authors.initials: P
authors.lastname: Safaie
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Mugilan
authors.initials: M
authors.lastname: Poongkunran
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Kuang
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Asad
authors.initials: A
authors.lastname: Javaid
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Carl
authors.initials: C
authors.lastname: Jacobs
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pohlmann
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Imad
authors.initials: I
authors.lastname: Nasser
authors.affiliation: Parham Safaie, Mugilan Poongkunran, Ping-Ping Kuang, Asad Javaid, Daryl TY Lau, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Daryl T Y
authors.initials: DT
authors.lastname: Lau
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000032:analysis*; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens
keywords: Chronic hepatitis B; Hepatitis B core antigen; Hepatitis B surface antigen; Hepatitis B virus; Hepatocellular carcinoma