HepB-CpG vaccination: An alternate strategy to life long antiviral therapy in patients transplanted for chronic Hepatitis B

Nucleoside analogue (NA) prophylaxis is given indefinitely after liver transplantation for chronic hepatitis B (CHB). We evaluated if antiviral therapy can be discontinued after vaccination with the immune adjuvanted HepB-CpG vaccine. Methods: Two groups of liver recipients discontinued NA when anti-HBs levels >100 mIU/mL. Group 1 had previously received 3 doses of vaccine and were given periodic vaccine boosters to maintain this anti-HBs level. Group 2 participated in a 48 week protocol where the same 3 dose series was followed by one or two boosters based on anti-HBs level at week 20. HBV recurrence was considered to be reappearance of both HBsAg and HBV DNA by conventional methods of detection. Selected sera in both groups were analyzed for pregenomic (pg) RNA and HBsAg by an ultrasensitive qualitative assay. Results: Twenty liver recipients taking NA prophylaxis were included, 5 in Group 1 and 15 in Group 2. Most were over age 60 and were transplanted more than 10 years previously. Fifteen (75%) were withdrawn from NA after vaccination, 4 in Group 1 and 11 in Group 2. Fourteen (93%) remained free of recurrence during a median period of 41.3 months (Group 1) and 12 months (Group 2). Transient recurrence occurred in a Group 1 participant found to have pgRNA 18 months earlier. Another Group 1 individual failed vaccination but was found to be pgRNA and HBsAg positive in all samples. One Group 2 participant was HBsAg positive at baseline by the ultrasensitive assay and subsequently developed mild self-limiting viremia after NA discontinuation. Conclusions: Discontinuation of NA is frequently possible after HepB-CpG vaccination. Long term protection is sustainable with periodic boosters. New biomarkers for HBV allow earlier detection of underlying viral transcription and may promote better understanding of vaccine failure.