Successful hepatitis B vaccination in liver transplant recipients with donor-specific hyporesponsiveness

Abstract

Summary Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)‐related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV‐infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV‐related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor‐specific hyporesponse with a well‐maintained response to the third‐party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third‐party stimulus were unable to do so. Thus, inducing an anti‐donor‐specific immunosuppressive status by minimizing immunosuppression should enable post‐transplant HBV vaccination to be a promising prophylactic strategy.

Different effect of HBV vaccine after liver transplantation between chronic HBV carriers and non-HBV patients who received HBcAb-positive grafts

“…There is no direct evidence to confirm this speculation, so further investigation will be necessary. In one recent report by Tahara et al [29], relatively good HBV vaccine response was shown even in HBV chronic carrier cases. They monitored patients' immune status by a mixed lymphocyte reaction assay using carboxyfluorescein (CFSE), and showed that vaccine responses were correlated to the level where only immune response of antidonor lymphocyte was suppressed and that of anti-third party lymphocyte was maintained, irrespective of trough levels of calcineurin inhibitors.…”

“…HBsAb [100 IU/l without HBIg administration for more than 3 months was judged to indicate success of this vaccine protocol according to the previous reports for HBV prophylaxis [11,26,27] and vaccine effect [28,29]. If this level could be attained, lamivudine treatment could be stopped.…”

Discontinuation of Hepatitis B Immunoglobulin by Long-term Hepatitis B Vaccine Inoculation in Preventing Hepatitis B Recurrence After Liver Transplantation

“…By assessing a recipient's immunosuppressive status with the precise manner, Tahara et al [14] reported good results of vaccination, giving a 64.7% response rate. They assessed the recipient's immunosuppressive status using donor lymphocyte and the third-party lymphocyte, and by keeping the anti-donor-specific immunosuppression, they adjusted the dose of immunosuppressive agents.…”

“…Recently, this indicator has been widely used not only in LT, but also in various organ transplantations. In our institution, the ImmuKnow assay has been introduced for LDLT recipients since 2011 [14,15]. By using this assay, LDLT recipients are categorized into the three established zones of immune response: low response, moderate response, and strong response.…”

The detection of (total and ccc) HBV DNA in liver transplant recipients with hepatitis B vaccine against HBV reinfection

“…[8][9][10][11] Active immunization with standard hepatitis B vaccines in these patients is considered a promising substitute to the current treatment strategy, although the results of this new strategy have been controversial. [12][13][14][15][16][17][18][19][20][21][22] Some studies have reported that responders to hepatitis B vaccination, defined as patients with anti-HBs, should stop taking HBIG and/or antiviral agents. 12,16,17,[20][21][22] However, the safety of discontinuing HBIG and/or antiviral agents in responders remains unclear.…”