title: [Analysis of the relationship between hepatitis B virus precore and basal core promoter mutations and acute-on-chronic liver failure].
abstract: OBJECTIVE
  To analyze the relationship between hepatitis B virus (HBV) precore (PC) and basal core promoter (BCP) mutations and HBV-related acute-on-chronic liver failure (HB-ACLF).
  
  
  METHODS
  Forty-four patients with HB-ACLF and 28 patients with chronic hepatitis B (CHB; used as controls) were enrolled and venous blood samples were collected from all individuals. The PC and BCP gene fragments were amplified by nested PCR. HBV genotype and BCP/PC mutations were determined by direct sequencing and analysis by BioEdit (version 7.0.9.0). Ten of the HB-ACLF patients were selected for follow-up (range: 2-8 weeks), which included once weekly sera collection to determine the relation of mutations and treatment response. Serum levels of HBV DNA were measured by real-time PCR assay, and alanine aminotransferase, total bilirubin, creatinine and albumin were measured by standard biochemical assay and used to determine the MELD score.
  
  
  RESULTS
  All 44 HB-ACLF patients were infected with HBV genotype C. In the CHB group, 26 patients were infected with genotype C and two with genotype B. Single mutations (A1762T, G1764A, T1753V, G1896A, and G1899A) and combined mutations (A1762T + G1764A, G1896A + G1899A, T1753V+ A1762T + G1764A, G1896A + G1899A + A1762T + G1764A, and A1762T + G1764A + G1896A) were more frequently detected in HB-ACLF patients than in CHB patients (P less than 0.05). A significantly higher proportion of PC/BCP wild-type sequences was found in patients with CHB than in patients with HB-ACLF (17.9% vs. 2.3%; x² = 5.440, P = 0.020). The proportion of patients carrying both PC and BCP mutations was significantly higher in HB-ACLF patients than in CHB patients (79.6% vs. 39.3%; x² = 12.021, P = 0.001). The proportion of patients carrying only BCP mutation was 42.9% in the CHB group and 20.5% in the HB-ACLF group (x² = 4.157, P = 0.041). No occurrences of only PC mutation were detected in either the CHB or HB-ACLF group. The combined mutations were present in all 10 of the HB-ACLF follow-up patients. Mutations G1899A, T1753V, and A1846T were correlated with disease recovery. Significant decreases in the MELD score were accompanied by decreases in the A1846T mutation.
  
  
  CONCLUSIONS
  Significantly more HB-ACLF patients carried HBV with mutations in the PC and BCP than CHB patients. Moreover, more HB-ACLF patients carried HBV with PC + BCP combined mutations and PC mutation only. The G1899A, T1753C, and A1846T mutations were associated with HB-ACLF response to treatment and improvement in liver function.
authors.affiliation: Department of Hepatology, the Third Central Clinical College of Tianjin Medical University, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Yan-zhen
authors.initials: YZ
authors.lastname: Pei
authors.forename: Zhen-gang
authors.initials: ZG
authors.lastname: Zhao
authors.forename: Ying-tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Jing
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D058625:End Stage Liver Disease; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D017093:Liver Failure / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens