title: Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study.
abstract: To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC.
  
  
  
  HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs.
  
  
  
  OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different.
  
  
  
  The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description.
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Onorato
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.|Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iodice
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Starace
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Minichini
authors.affiliation: Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Farella
authors.affiliation: Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Liorre
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.|Infectious Diseases Unit, Caserta Hospital, Caserta, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Filippini
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
authors.affiliation: Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: de Stefano
mesh_terms: D000368:Aged; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006509:Hepatitis B / Q000150:complications*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: HBsAg mutants; anti-HBc positivity; hepatocellular carcinoma; liver cirrhosis; occult HBV infection