Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis.
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.
Lenci
Ilaria
I
Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Via Montpellier 1-00133 Rome, Italy. ilaria.lenci@med.uniroma2.it
Marcuccilli
Fabio
F
Tisone
Giuseppe
G
Di Paolo
Daniele
D
Tariciotti
Laura
L
Ciotti
Marco
M
Guenci
Tania
T
Perno
Carlo Federico
CF
Angelico
Mario
M
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
D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral