Association of core promoter/precore mutations and viral load in e antigen-negative chronic hepatitis B patients.
Apart from core promoter A1762T/G1764A and precore G1896A mutations, other hepatitis B virus (HBV) mutants are detected in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to determine the effects of those mutants on clinical manifestation and viral loads of genotypes B and C HBV. Seventy-nine HBeAg-negative CHB patients with hepatitis flare were enrolled in this study and their HBV precore/core region were sequenced. Serial biochemical profiles and viral loads were assessed and compared. Fifty-three patients (67%) were infected by genotype B HBV and 26 (33%) were infected by genotype C HBV. The clinical manifestation and HBV viral loads were comparable between the two groups. However, genotype B was significantly associated with precore G1896A mutation (92.5%), and more mutations within nucleotide 1809-1817 were detected in patients infected by genotype B as compared with those infected by genotype C (18.9%vs 3.8%). Most of the cases had mutations at the -2, -3 or -5 position from the precore AUG initiation codon. Triple core promoter mutations T1753C/A1762T/G1764A [corrected] appeared to be linked to genotype C rather than genotype B HBV (19.2%vs 1.9%; P = 0.013). In multivariate analysis, the presence of either triple core promoter 1753/1762/1764 mutation or nucleotide 1809-1817 mutation was the only factor associated with lower HBV viral load (<70 Meq/mL) (odds ratio = 9.01; 95% CI 1.11-71.43; P = 0.04). In conclusion, minor HBV variants with mutations in the core promoter and precore region were detectable in genotypes B and C. Such HBV variants are genotype specific and related to viraemia levels.
Huang
Y-H
YH
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Wu
J-C
JC
Chang
T-T
TT
Sheen
I-J
IJ
Huo
T-I
TI
Lee
P-C
PC
Su
C-W
CW
Lee
S-D
SD
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000097:blood / Q000276:immunology / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D019562:Viral Load
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D012367:RNA, Viral; D000410:Alanine Transaminase