Early HBV and HDV kinetics in patients undergoing liver transplantation

Abstract

Background and Aims

Hepatitis B virus (HBV) graft infection occurs after liver transplantation (LT) despite viral source removal and prophylactic treatment. We aimed to elucidate mechanisms and timing of HBV/hepatitis delta virus (HDV) reinfection by analysing early viral kinetics in serum and tissue.

Methods

Serial serum and liver samples were prospectively collected peri- and post-transplant in 12 HBV (5 HDV coinfected) LT recipients. Kinetics of different viral markers were analysed.

Results

HBV-DNA, HDV-RNA, HBsAg and HDAg were detected in all liver explants, while cccDNA was only detectable in HBV monoinfected patients. Residual serum HBV-DNA was detectable before LT in 5 patients but became undetectable a few hours after the anhepatic phase. HBsAg levels were low (<3logIU/mL) in HBV monoinfected patients and cleared fast (within 5 days) in those receiving hepatitis B immune globulin (HBIG) compared to those who did not (within 6 months). In HDV coinfected patients (all receiving HBIG), HBsAg clearance was fast (within 12 hours) if baseline HBsAg <3logIU/mL and slow (within 6 months) if baseline HBsAg >3logIU/ml. HDV-RNA kinetics paralleled that of HBsAg. Post-transplant biopsies, obtained at reperfusion, 3 and 12 months after LT, tested negative for all viral markers (including cccDNA), except for one patient with detectable intrahepatic HDV-RNA and HDAg at 3 months post-LT with undetectable HBV and HDV serum markers.

Conclusion

Despite varying kinetics of HBsAg clearance following LT, we did not detect intrahepatic HBV markers at different time points following transplantation. In contrast, HDV could be sporadically detected in the liver graft, highlighting the need to evaluate new prophylactic strategies in HDV coinfected patients awaiting LT.