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.