title: Prevalence of herpesviridae and hepatitis virus sequences in the livers of patients with fulminant hepatitis of unknown etiology in Japan.
abstract: BACKGROUND
  Fulminant non-A, non-B, non-C hepatitis has a high mortality rate, making the identification of its causative agent imperative. Cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, and herpes simplex virus are all members of the herpesviridae family that are associated with fatal hepatic failure. We investigated the involvement of herpesviridae and hepatitis virus in the pathogenesis of fulminant hepatitis.
  
  
  METHODS
  The study participants consisted of 11 patients with fulminant hepatitis and 11 with acute hepatitis negative for known hepatitis viral markers and any other liver diseases. Viral DNA was extracted from liver tissues and amplified. In situ hybridization was then performed for 1 patient to detect viral DNA and RNA, and viral protein was localized by monoclonal antibodies.
  
  
  RESULTS
  Human herpesvirus-6 was detected in liver tissues from seven patients, (five children and two adults) with fulminant hepatitis and two patients with acute hepatitis. Two patients with fulminant hepatitis also had cytomegalovirus in the liver. Although Epstein-Barr virus and herpes simplex virus were detected in the patients with fulminant hepatitis, they were not specific to these patients. In situ hybridization in one of the patients localized DNA and RNA of human herpesvirus-6 in hepatocyte nuclei, and an envelope antigen of this virus was detected in hepatocyte cytoplasm.
  
  
  CONCLUSIONS
  Human herpesvirus-6 was frequently detected in Japanese pediatric patients with fulminant non-A, non-B, non-C hepatitis. Although the significance of human herpesvirus-6 in liver pathogenesis remains unclear, this virus may replicate in hepatocytes in some patients with acute onset hepatitis.
authors.affiliation: Institute of Gastroenterology, Tokyo Women's Medical University, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Naritomi
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanai
authors.forename: Miho
authors.initials: M
authors.lastname: Ogawa
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Torii
authors.forename: Naoaki
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D002648:Child; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006518:Hepatitis Viruses / Q000302:isolation & purification; D006564:Herpesviridae / Q000302:isolation & purification; D015654:Herpesvirus 6, Human / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008099:Liver / Q000821:virology*; D017093:Liver Failure / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral