title: Genomic change in hepatitis B virus associated with development of hepatocellular carcinoma.
abstract: OBJECTIVE
  To determine the genomic changes in hepatitis B virus (HBV) and evaluate their role in the development of hepatocellular carcinoma (HCC) in patients chronically infected with genotype C HBV.
  
  
  METHODS
  Two hundred and forty chronic hepatitis B (CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced using the direct sequencing method.
  
  
  RESULTS
  All of the subjects were infected with genotype C HBV. Out of 240 CHB patients, 25 (10%) had C1653T and 33 (14%) had T1753V mutation in X region; 157 (65%) had A1762T/G1764A mutations in BCP region, 50 (21%) had G1896A mutation in precore region and 67 (28%) had pre-S deletions. HCC occurred in 6 patients (3%). The prevalence of T1753V mutation was significantly higher in patients who developed HCC than in those without HCC. The cumulative occurrence rates of HCC were 5% and 19% at 10 and 15 years, respectively, in patients with T1753V mutant, which were significantly higher than 1% and 1% in those with wild type HBV (P < 0.001).
  
  
  CONCLUSIONS
  The presence of T1753V mutation in HBV X-gene significantly increases the risk of HCC development in patients chronically infected with genotype C HBV.
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Danbi
authors.initials: D
authors.lastname: Lee
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Heather
authors.initials: H
authors.lastname: Lyu
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Priya
authors.initials: P
authors.lastname: Mathews
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jaffee
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
authors.forename: Soo Hyung
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Chronic hepatitis B; Genomic change; Genotype C; Hepatitis B virus; Hepatocellular carcinoma