title: Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality.
abstract: OBJECTIVE
  Molecular evolutionary analysis based on coalescent theory can provide important insights into epidemiologic processes worldwide. This approach was combined with analyses of the hepatitis C virus (HCV) epidemiologic-historical background and HCV-related hepatocellular carcinoma (HCC) in different countries.
  
  
  METHODS
  The HCV gene sequences of 131 genotype 1b (HCV-1b) strains from Japan, 38 HCV-1a strains from the United States, 33 HCV-1b strains from Spain, 27 HCV-3a strains from the former Soviet Union (FSU), 47 HCV-4a strains from Egypt, 25 HCV-5a strains from South Africa, and 24 HCV-6a strains from Hong Kong isolated in this study and previous studies were analyzed.
  
  
  RESULTS
  The coalescent analysis indicated that a transition from constant size to rapid exponential growth (spread time) occurred in Japan in the 1920s (HCV-1b), but not until the 1940s for the same genotype in Spain and other European countries. The spread time of HCV-1a in the United States was estimated to be in the 1960s; HCV-3a in the FSU, HCV-5a in South Africa, and HCV-6a in Hong Kong in the 1960s, mid-1950s, and late 1970s, respectively. Three different linear progression curves were determined by analysis of the relationship between HCV seroprevalence and HCC mortality in different geographic regions; a steep ascent indicated the greatest progression to HCC in Japan, a near horizontal line indicated the least progression in the United States and the FSU, and an intermediate slope was observed in Europe.
  
  
  CONCLUSIONS
  These findings strongly suggest that the initial spread time of HCV is associated with the progression dynamics of HCC in each area, irrespective of genotype.
authors.affiliation: Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Fuat
authors.initials: F
authors.lastname: Kurbanov
authors.forename: Shuhei
authors.initials: S
authors.lastname: Mano
authors.forename: Etsuro
authors.initials: E
authors.lastname: Orito
authors.forename: Victor
authors.initials: V
authors.lastname: Vargas
authors.forename: Juan I
authors.initials: JI
authors.lastname: Esteban
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Anna
authors.initials: A
authors.lastname: Kramvis
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kew
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Smuts
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Netesov
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality*; D008297:Male; D008875:Middle Aged