Hepatitis B virus genotype and basal core promoter/precore mutations are associated with hepatitis B-related acute-on-chronic liver failure without pre-existing liver cirrhosis.
The study was undertaken to investigate the features and clinical implications of hepatitis B virus (HBV) genotypes, basal core promoter (BCP) and precore (PC) mutations in hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Samples from 75 patients with HB-ACLF and without pre-existing liver cirrhosis and 328 age-matched patients with chronic hepatitis B (CHB) were analyzed. HBV genotype and BCP/PC mutations were determined by direct sequencing. Mutations at 8 sites of the BCP/PC region were compared between the two groups of patients. A significantly higher ratio of genotype B to C was found in patients with HB-ACLF than in patients with CHB (30.7-69.3% vs 16.5-82.6%, P < 0.01). Single mutations including T1753V (C/A/G), A1762T, G1764A, G1896A and G1899A and triple mutations T1753V/A1762T/G1764A and A1762T/G1764A/C1766T (or T1768A) were more frequently detected in patients with HB-ACLF than in patients with CHB. Correspondingly, BCP/PC wild-type sequences were absent in patients with HB-ACLF in contrast to 27.1% in patients with CHB. The BCP/PC mutations were found to be associated with increased HBeAg negativity, higher alanine aminotransferase level and lower viral load. Patients with HB-ACLF infected with the PC mutant virus had a higher mortality. The findings suggest that patients with CHB infected with genotype B with BCP/PC mutations were more likely to develop HB-ACLF than those with genotype C with wild-type BCP/PC regions, and patients with HB-ACLF with the PC mutation had increased risk of a fatal outcome.
Ren
X
X
Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, Beijing 302 Hospital, Beijing, China.
Xu
Z
Z
Liu
Y
Y
Li
X
X
Bai
S
S
Ding
N
N
Zhong
Y
Y
Wang
L
L
Mao
P
P
Zoulim
F
F
Xu
D
D
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000097:blood; D058625:End Stage Liver Disease / Q000235:genetics* / Q000821:virology; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D055815:Young Adult
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D011498:Protein Precursors