Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure.
OBJECTIVE
To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features.


METHODS
Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54-1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant.


CONCLUSIONS
Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.
Xu
Zhihui
Z
Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, Beijing 100039, China.
Ren
Xiaoqiang
X
Liu
Yan
Y
Li
Xiaodong
X
Bai
Siyu
S
Zhong
Yanwei
Y
Wang
Lin
L
Mao
Panyong
P
Wang
Huifen
H
Xin
Shaojie
S
Wong
Vincent Wai-Sun
VW
Chan
Henry Lik-Yuen
HL
Zoulim
Fabien
F
Xu
Dongping
D
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044466:Asian People; D001663:Bilirubin / Q000097:blood; D058625:End Stage Liver Disease / Q000097:blood / Q000821:virology*; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000473:pathology* / Q000821:virology*; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase; D001663:Bilirubin