title: Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan.
abstract: OBJECTIVE
  The mortality due to hepatocellular carcinoma (HCC) has ranged widely in various areas of Japan since 30 years ago and the incidence was particularly high in once Schistosoma japonicum (Sj)-endemic areas. Our aim was to estimate the spread time of hepatitis C virus (HCV) infection in the past with possible relevance to a higher incidence of HCC in once Sj-endemic than Sj-nonendemic areas.
  
  
  METHODS
  During 2001, 131 strains of HCV-1b were obtained from patients in three previously Sj-endemic areas, as well as Sj-nonendemic areas in Japan and a cross-sectional study was conducted on them with molecular evolutionary analyses.
  
  
  RESULTS
  A phylogenetic tree reconstructed on HCV-1b sequences in the NS5B region disclosed 2 independent clusters for Sj-positive and -negative groups with a high bootstrap value. The estimated effective number of HCV-infections indicated a transition from quiescence to rapid exponential growth in the 1920s among patients with schistosomiasis, which is 20 years earlier than that among patients without schistosomiasis.
  
  
  CONCLUSIONS
  The estimated spread time in previously Sj-endemic areas in Japan coincides with injection treatment for Sj since 1921. A high incidence of HCC there would be attributed to a long duration of HCV infection since 1920s.
authors.affiliation: Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kousuke
authors.initials: K
authors.lastname: Hanada
authors.forename: Etsuro
authors.initials: E
authors.lastname: Orito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Akahane
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Gojobori
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D019143:Evolution, Molecular; D005260:Female; D016174:Hepacivirus / Q000145:classification; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D010802:Phylogeny; D012554:Schistosomiasis japonica / Q000150:complications* / Q000188:drug therapy