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.

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.