title: Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis.
abstract: BACKGROUND
  Life-long prophylaxis against HBV recurrence is recommended in patients transplanted for HBV-related disease. The risk of HBV reactivation is due to persistence of covalently closed circular (ccc) DNA in hepatocytes. Whether cccDNA persists in livers of long-term transplant survivors who received conventional prophylaxis is unknown.
  
  
  OBJECTIVE
  To investigate the presence of intrahepatic total and cccDNA in transplanted patients with no evidence of biochemical markers of HBV recurrence.
  
  
  METHODS
  Intrahepatic total and cccDNA were assessed using sensitive nested and real-time PCR from 44 HBsAg-positive patients (75% male; mean age 55.2+/-8.9 years) who had undetectable serum HBV-DNA at transplant. The mean follow-up after transplant was 88.3 months (range, 18-159).
  
  
  RESULTS
  One patient underwent HBV recurrence after transplant and was the only who tested positive for both intrahepatic total HBV-DNA and cccDNA. Of the 43 patients negative for all serological markers of HBV infection, only 2 tested positive for intrahepatic total HBV-DNA, but none for cccDNA.
  
  
  CONCLUSIONS
  Most patients with undetectable HBV-DNA at transplant, who received conventional HBV prophylaxis, have no evidence of intrahepatic total HBV-DNA and cccDNA. cccDNA should be considered a new additional diagnostic tool, also to identify patients at low risk of HBV recurrence after liver transplantation.
authors.affiliation: Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Via Montpellier 1-00133 Rome, Italy. ilaria.lenci@med.uniroma2.it
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lenci
authors.forename: Fabio
authors.initials: F
authors.lastname: Marcuccilli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tisone
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Paolo
authors.forename: Laura
authors.initials: L
authors.lastname: Tariciotti
authors.forename: Marco
authors.initials: M
authors.lastname: Ciotti
authors.forename: Tania
authors.initials: T
authors.lastname: Guenci
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D004270:DNA, Circular / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000628:therapy; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D007165:Immunosuppression Therapy; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000821:virology; D008103:Liver Cirrhosis / Q000209:etiology / Q000628:therapy; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D017741:Survivors; D014611:Vaccination
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral