title: [Relationship between metastasis or recurrence of hepatocellular carcinoma and hepatitis B virus DNA or double mutation at 1762/1764 in the basic core promoter].
abstract: OBJECTIVE
  To study the relationship between metastasis or recurrence of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) DNA load or the presence of double mutation at 1762/1764 in the basic core promoter (BCP).
  
  
  METHODS
  One-hundred-and-fifty-seven patients with HCC were included in the study. Events of tumor metastasis or recurrence were recorded during 120 weeks of clinical follow-up after treatment by surgery or transarterial chemoembolization (TACE). The 1-year follow-up included monthly alpha fetoprotein (AFP) measurement and abdominal ultrasonography (US), as well as helical computed tomographic (CT) scan performed every 3 months. Follow-up beyond 1-year (surveillance) included AFP measurement and abdominal US every 2 months and helical CT scan every 6 months. Suspected metastasis or recurrence was investigated by hepatic angiography and confirmed according to the combined imaging findings. Serum HBV DNA level was measured by real-time PCR. HBV genotypes were determined by PCR-restriction fragment length polymorphism analysis.
  
  
  RESULTS
  Of the 157 HCC cases 110 experienced tumor metastasis or recurrence; the cumulative probability of post-treatment HCC metastasis or recurrence was 4 (2.55%) at week 12, 14 (8.92%) at week 24, 28 (17.83%) at week 48, 64 (40.76%) at week 72, 92 (58.60%) at week 96, and 110 (70.06%) at week 120. Multivariate analysis indicated that both the BCP 1762/1764 double mutations and HBV DNA levels were risk factors for HCC recurrence or metastasis. In particular, the incidence of HCC recurrence or metastasis increased with baseline serum HBV DNA levels in a dose-response manner, ranging from 8/19 (42.1%) for less than 3 log10 copies/ml HBV DNA to 35/61 (57.3%) for 3-5 log10 copies/ml and 67/77 (87.0%) for more than 5 log10 copies/ml. After adjusting for potential confounders, serum HBV DNA level remained independently associated with HCC metastasis or recurrence. HCC recurrence or metastasis occurred in 22/43 (51.2%) of patients without BCP 1762/1764 mutations and 88/114 (77.2%) of patients with BCP 1762/1764 mutations. The adjusted odds ratio for patients infected with BCP 1762/1764 double mutation HBV, compared with those infected with non-BCP 1762/1764 mutation HBV, was 5.264 (95% CI: 1.436-12.574, P less than 0.05).
  
  
  CONCLUSIONS
  Infection with HBV carrying the BCP 1762/1764 double mutation and presence of high HBV DNA load are independent risk factors for developing HCC metastasis or recurrence after surgery or TACE.
authors.affiliation: Department of Infectious Diseases, the First Hospital Affiliated to Suzhou University, Suzhou 215004, China.
authors.forename: You-wen
authors.initials: YW
authors.lastname: Tan
authors.forename: Yuan-hai
authors.initials: YH
authors.lastname: Zhang
authors.forename: Wei-jun
authors.initials: WJ
authors.lastname: Jiang
authors.forename: Mao-ying
authors.initials: MY
authors.lastname: Xing
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Man
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Mao
authors.forename: Guo-hong
authors.initials: GH
authors.lastname: Ge
authors.forename: Cui-song
authors.initials: CS
authors.lastname: Wu
authors.forename: Mei-qin
authors.initials: MQ
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Xing-pei
authors.initials: XP
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011401:Promoter Regions, Genetic; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens