Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis

Lenci, Ilaria; Marcuccilli, Fabio; Tisone, Giuseppe; Di Paolo, Daniele; Tariciotti, Laura; Ciotti, Marco; Guenci, Tania; Perno, Carlo Federico; Angelico, Mario

doi:10.1016/j.dld.2009.12.003

« Previous Next »Digestive and Liver Disease
Volume 42, Issue 8 , Pages 578-584, August 2010

Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis

Ilaria Lenci
- Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Via Montpellier 1-00133 Rome, Italy
- Corresponding author at: Chair of Gastroenterology, Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Via Montpellier 1-00133 Rome, Italy. Tel.: +39 06 72596803.
Fabio Marcuccilli
- Laboratory of Molecular Virology, Tor Vergata Medical School, Rome, Italy
Giuseppe Tisone
- Liver Transplant Unit, Tor Vergata Medical School, Rome, Italy
Daniele Di Paolo
- Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Via Montpellier 1-00133 Rome, Italy
Laura Tariciotti
- Liver Transplant Unit, Tor Vergata Medical School, Rome, Italy
Marco Ciotti
- Laboratory of Molecular Virology, Tor Vergata Medical School, Rome, Italy
Tania Guenci
- Laboratory of Molecular Virology, Tor Vergata Medical School, Rome, Italy
Carlo Federico Perno
- Laboratory of Molecular Virology, Tor Vergata Medical School, Rome, Italy
Mario Angelico
- Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Via Montpellier 1-00133 Rome, Italy

Received 15 September 2009; accepted 6 December 2009. published online 25 January 2010.

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.

Aim

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.

Abbreviations: LT, liver transplantation, DNA, deoxyribonucleic acid, cccDNA, covalently closed circular DNA, total HBV-DNA, including relaxed circular DNA intermediate e forms and cccDNA, rcDNA, relaxed-circular DNA, HBIg, anti-hepatitis B specific immunoglobulins, HBV, hepatitis B virus, HBsAg, hepatitis B surface antigen, HBcAb, hepatitis B core antibodies, HBV-DNA, hepatitis B virus DNA, Anti-HBs, antibodies against hepatitis B surface antigen, HCV, hepatitis C virus, HDV, hepatitis D virus, ALT, alanine amine transferases, PCR, polymerase chain reaction, HCC, hepatocellular carcinoma, PNF, primary nonfunction