title: High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma.
abstract: OBJECTIVE
  We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC).
  
  
  METHODS
  A prospective cohort of patients infected with chronic HBV in a surveillance program for HCC since 1997 was studied. Ultrasound and alpha-fetoprotein evaluation were regularly performed to detect HCC. Risk factors for HCC and the relationship between HBV DNA and HBV genotypes were determined.
  
  
  RESULTS
  Among 1,006 patients with a median follow-up of 7.7 years, 86 patients (8.5%) developed HCC. With reference to the low HBV DNA stratum (log HBV DNA </= 4.5 copies/mL), the hazard ratio for HCC of the intermediate HBV DNA stratum (log HBV DNA > 4.5 to 6.5 copies/mL) was 1.62 (95% CI, 1.05 to 2.48; P = .027) and that of the high HBV DNA stratum (log HBV DNA > 6.5 copies/mL) was 2.73 (95% CI, 1.76 to 4.25; P < .001). Among patients with genotyping results, 330 patients had HBV genotype B and 439 patients had HBV genotype C (94 subgenotype Ce and 345 subgenotype Cs). With reference to HBV genotype B, HBV subgenotype Ce has the highest risk of HCC (hazard ratio = 2.75; 95% CI, 1.66 to 4.56; P < .0001) and HBV subgenotype Cs has intermediate risk (hazard ratio = 1.70; 95% CI, 1.09 to 2.64; P = .020). On multivariate analysis, HBV DNA, HBV genotypes, liver cirrhosis, male sex, older age, and lower serum albumin were independent risk factors of HCC.
  
  
  CONCLUSIONS
  High HBV DNA level and HBV genotype C, particularly subgenotype Ce, increased the risk of HCC in chronic hepatitis B.
authors.affiliation: Department of Clinical Oncology, Sir YK Pao Center for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
authors.forename: Chi-Hang
authors.initials: CH
authors.lastname: Tse
authors.forename: Frankie
authors.initials: F
authors.lastname: Mo
authors.forename: Jane
authors.initials: J
authors.lastname: Koh
authors.forename: Vincent Wai-Sun
authors.initials: VW
authors.lastname: Wong
authors.forename: Grace Lai-Hung
authors.initials: GL
authors.lastname: Wong
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam Chan
authors.forename: Winnie
authors.initials: W
authors.lastname: Yeo
authors.forename: Joseph Jao-Yiu
authors.initials: JJ
authors.lastname: Sung
authors.forename: Tony Shu-Kam
authors.initials: TS
authors.lastname: Mok
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D019562:Viral Load