Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality.
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.
Tanaka
Yasuhito
Y
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Kurbanov
Fuat
F
Mano
Shuhei
S
Orito
Etsuro
E
Vargas
Victor
V
Esteban
Juan I
JI
Yuen
Man-Fung
MF
Lai
Ching-Lung
CL
Kramvis
Anna
A
Kew
Michael C
MC
Smuts
Heidi E
HE
Netesov
Sergey V
SV
Alter
Harvey J
HJ
Mizokami
Masashi
M
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