title: Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma.
abstract: BACKGROUND
  Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients.
  
  
  METHODS
  Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of alpha fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy.
  
  
  RESULTS
  In total, 426 patients were followed up for 1664 person years; median 225 (range 12-295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14-236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39-23.89; p<0.001) and 2.84 (95% CI 1.05-7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period.
  
  
  CONCLUSIONS
  Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.
authors.affiliation: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing St, Shatin, Hong Kong, China. hlychan@cuhk.edu.hk
authors.forename: H L-Y
authors.initials: HL
authors.lastname: Chan
authors.forename: A Y
authors.initials: AY
authors.lastname: Hui
authors.forename: M L
authors.initials: ML
authors.lastname: Wong
authors.forename: A M-L
authors.initials: AM
authors.lastname: Tse
authors.forename: L C-T
authors.initials: LC
authors.lastname: Hung
authors.forename: V W-S
authors.initials: VW
authors.lastname: Wong
authors.forename: J J-Y
authors.initials: JJ
authors.lastname: Sung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors