The Case for Revaccinating Against HBV After Eradicating HCV

Hepatitis B vaccine non-responders with chronic HCV infection were found likely to respond to revaccination after successful treatment of the HCV, in what investigators characterize as the first study to evaluate how curing HCV affects immune response to HBV vaccination.

"Despite guideline recommendations that all individuals with chronic HCV infection be immunized for HBV, rates of immunization among this population remain low," observed principal investigator, Jose Debes, MD, PhD, MS, Department of Medicine, University of Minnesota, Minneapolis, MN, and colleagues.

"Additionally, patients with chronic HCV infection may not respond to HBV vaccination as efficiently as non-infected patients," Debes and colleagues noted.

They acknowledged that post-vaccination testing after an initial series is generally not recommended in the general populations, but suggest it could be warranted for those at high risk for HBV such as patients with HCV or who are immunocompromised to identify those who should be revaccinated.

Citing several studies which have shown normalization of immune response after 3 months of sustained virologic response (SVR) following direct-acting antiviral (DAA) treatment of HCV infection, the investigators conducted this prospective study to ascertain response to re-vaccination for HBV after achieving SVR from HCV.

The investigators identified 34 patients in clinic records from between April 2018 and October 2019 who had achieved SVR at 12 weeks following HCV treatment, had negative Hepatitis B surface antigen (HBsAg), and had previously received at least 2 HBV vaccines without documented Hepatitis B surface antibody (HBsAb) development. Each had remained HBsAb negative at time of study enrollment.

The study participants were 18 years or older (median 61.5 years, Interquartile range 55-65), and most were male (68%) and black (59%).Five (15%) were co-infected with HIV.The median time from last prior HBV vaccination to first re-vaccination was 4.25 years (IQR 2-11).

The 34 study participants who had received successful DAA treatment for HCV infection were revaccinated against HBV with either 3 doses of ENGERIX-B or 2 doses of HEPLISAV-B.Of the 34, 31 underwent follow-up ABsAb testing, with 21 producing a reactive HBsAb (67.7%), 8 were non-reactive (25.8%) and 2 (6.5%) had equivocal results.Two participants did not complete the full HBV vaccination series.

Although this was a small cohort, the investigators reported achieving between 68-74% HBsAb reactivity. This rate is lower than the estimated 90% among larger populations of HCV negative individuals, but they emphasize that it is significantly better than the initial non-response of their participants. There was no apparent effect of HIV co-infection--nor of advanced fibrosis or being on hemodialysis—on development of HBsAb following revaccination.

Debes discussed their study with Contagion, noting that while a larger study is being planned, these results do support a recommendation for revaccination against HBV after HCV erradication.

"At this point, I would recommend testing HCV-positive individuals for HBV protection (HBsAb) and if negative, revaccinating after DAA treatment," Debes advised. "Based on previous studies, it seems that after 3 months of SVR the immune system returns to some normality, and this would be a good time to vaccine—(although) more research is needed on this."

"We need a larger study to confirm the effect we found, and we need better studies to understand when the immune system returns to normal, and we need further understanding on what are the changes that lead HCV-positive patients to have a lower response to the HBV vaccine initially," Debes said.