title: Viral load, genotypes, and mutants in hepatitis B virus-related hepatocellular carcinoma: special emphasis on patients with early hepatocellular carcinoma.
abstract: OBJECTIVE
  The role of viral factors in the pathogenesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is still inconclusive. Whether virological features such as viral load or mutants might change with the progression of HCC remains unknown. A case-control study including patients with early HCC and HBsAg carriers who are presumed to be at the minimal potential of HCC as controls might better identify factors significantly associated with HCC development.
  
  
  METHODS
  Virological features were compared between 59 patients with early HCC (a solitary tumor of size ≤ 3 cm) and 101 patients with non-early HCC. A case-control study was performed by comparing 59 patients with early HCC and 1:2 age-matched inactive carriers with persistent normal alanine aminotransferase (ALT) levels.
  
  
  RESULTS
  HBV DNA levels, HBV genotypes, and the frequency of precore A1896 and basal core promoter T1762/A1764 mutations showed no significant difference between patients with early HCC and those with non-early HCC. In the case-control study, patients with early HCC had significantly higher HBV DNA levels, and higher frequencies of genotype C HBV and basal core promoter T1762/A1764 mutation, but a similar frequency of precore A1896 mutation. Multiple logistic regression analysis identified HBV DNA levels ≥ 2,000 IU/mL and basal core promoter T1762/A1764 mutation as being independent factors for HCC development. Additionally, there was a synergistic effect between high viral load and basal core promoter T1762/A1764 mutation on HCC development.
  
  
  CONCLUSIONS
  Virological features did not change significantly with the progression of HCC. HBV DNA levels ≥ 2,000 IU/mL and basal core promoter T1762/A1764 mutation were two independent viral factors for HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tung Hwa North Road, Taipei 10591, Taiwan. chiamingchu@yahoo.com.tw
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chu
authors.forename: Chen-Chun
authors.initials: CC
authors.lastname: Lin
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Lin
authors.forename: Deng-Yn
authors.initials: DY
authors.lastname: Lin
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000097:blood / Q000150:complications* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000410:Alanine Transaminase