title: Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection.
abstract: OBJECTIVE
  Occult hepatitis B virus (HBV) infection is characterized by persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative individuals. The clinical relevance of this peculiar infection is still under debate. In particular, the impact of occult HBV infection in cases of hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and molecular status of occult HBV in patients with HCC.
  
  
  METHODS
  We tested tumor tissues from 107 patients with HCC and the corresponding nontumor liver tissue from 72 of these patients for HBV DNA. We also examined liver specimens from 192 patients with chronic hepatitis. All cases were hepatitis B surface antigen negative. Covalently closed circular HBV genomes, HBV transcripts, and viral integrated forms were investigated in cases of HCC found positive for occult HBV.
  
  
  RESULTS
  Viral DNA was detected in 68 of 107 cases of HCC (63.5%) and in 63 of 192 cases of chronic hepatitis (32.8%) (P < 0.0001; odds ratio, 3.6; 95% confidence interval, 2.2-5.9). The significant association of occult HBV with HCC was irrespective of age, sex, and contemporary hepatitis C virus infection. Both integrated viral DNA and covalently closed circular HBV genomes were detected in patients with occult HBV. Moreover, the presence of free HBV genomes was associated with persistence of viral transcription and replication.
  
  
  CONCLUSIONS
  Our findings provide clear evidence that occult HBV is a risk factor for development of HCC and show that the potential mechanisms whereby overt HBV might induce tumor formation are mostly maintained in cases of occult infection.
authors.affiliation: Department of Internal Medicine, University of Messina, Messina, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pollicino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Squadrito
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cerenzia
authors.forename: Irene
authors.initials: I
authors.lastname: Cacciola
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Raffa
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxi
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Antonina
authors.initials: A
authors.lastname: Smedile
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiribelli
authors.forename: Erica
authors.initials: E
authors.lastname: Villa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Raimondo
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D004279:DNA, Viral