Comparison of genotypes C and D of the hepatitis B virus in Japan: a clinical and molecular biological study.
The genotype-related differences between genotype C and genotype D of the hepatitis B virus (HBV) remain unknown. The relationship was studied between the HBV genotypes and their clinical features, paying special attention to genotypes C and D. Serum samples from 413 HBV carriers were genotyped using an enzyme immunoassay (EIA) and by restriction fragment length polymorphism. The nucleotide sequences at the basic core promoter (BCP) and precore (PreC) regions were analysed by direct sequencing. The full genome sequences of three HBV genotype D cases were also examined. Almost all carriers with HBV genotype D were asymptomatic carriers (84.2%). Genotype D was not found in patients with liver cirrhosis and hepatocellular carcinoma. In contrast, carriers with genotype C had mainly chronic liver disease (63.2%; P<0.001). The ratio of hepatitis B e antigen (HBeAg)/anti-HBe was significantly higher in genotype C than in genotype D in the young age-matched group (P<0.01). The mutation at BCP (T1762, A1764) was significantly lower in genotype D than in genotype C among HBeAg-negative patients (P<0.05). The HBV full-genome sequences are very similar to certain HBV genotype D sequences from Europe. In conclusion, genotype C was associated with chronic liver disease, whereas genotype D was related to asymptomatic carriers with earlier HBeAg seroconversion. Thus, the outcome of chronic HBV infection may be different in persons infected with HBV genotypes C and D.
Duong
Tran Nhu
TN
Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Horiike
Norio
N
Michitaka
Kojiro
K
Yan
Chen
C
Mizokami
Masashi
M
Tanaka
Yasuhito
Y
Jyoko
Kouji
K
Yamamoto
Kazutoshi
K
Miyaoka
Hiroaki
H
Yamashita
Yoshimasa
Y
Ohno
Naofumi
N
Onji
Morikazu
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000821:virology; D002353:Carrier State / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D007564:Japan / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014758:Viral Core Proteins / Q000235:genetics; D014766:Viremia
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins