A case-control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae) and D.
There are two subtypes of hepatitis B virus genotype A (HBV/A) and they are provisionally designated Aa ("a" standing for Africa/Asia) and Ae ("e" for Europe). In a case-control study, 78 HBV/Aa, 78HBV/Ae, and 78HBV/D carriers from several countries were compared. The prevalence of HBe antigen (HBeAg) in serum was significantly lower in carriers of HBV/Aa than in carriers of HBV/Ae (31% vs. 49%; P = .033), with a difference more obvious in the carriers aged 30 years or younger (34% vs. 67%; P = .029). HBV DNA levels in the carriers of HBV/Aa (median, 3.46 log copies/mL; 95% CI, 2.93-3.95) were significantly lower than those of carriers of HBV/Ae (6.09 log copies/mL; 95% CI, 4.24-7.64) or of carriers of HBV/D (5.48 log copies/mL; 95% CI, 4.06-7.02), regardless of the HBeAg status (P < .001). The most specific and frequent substitutions in 54 HBV/Aa isolates were double substitutions for T1809 (100%) and T1812 (96%) immediately upstream of the precore initiation codon, which would interfere with the translation of HBeAg in HBV/Aa infections. They were not detected in 57 HBV/Ae or 61 HBV/D isolates examined. The double mutation in the core promoter (T1762/A1764) was more frequent in both HBV/Aa (50%) and HBV/Ae (44%) than in HBV/D isolates (25%; P < .01), whereas the precore mutation (A1896) occurred in HBV/D isolates only (48%; P < .0001). In conclusion, the clearance of HBeAg from serum may occur by different mechanisms in HBV/Aa, HBV/Ae, and HBV/D infections, which may influence clinical manifestations in the Western countries where both genotypes A and D are prevalent.
Tanaka
Yasuhito
Y
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Hasegawa
Izumi
I
Kato
Takanobu
T
Orito
Etsuro
E
Hirashima
Noboru
N
Acharya
Subrat K
SK
Gish
Robert G
RG
Kramvis
Anna
A
Kew
Michael C
MC
Yoshihara
Namiko
N
Shrestha
Santosh Man
SM
Khan
Mobin
M
Miyakawa
Yuzo
Y
Mizokami
Masashi
M
D001483:Base Sequence; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis; D005838:Genotype; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic
D004279:DNA, Viral; D006513:Hepatitis B e Antigens