Hepatitis B Vaccination After Living Donor Liver Transplantation
Hepatitis B Vaccination After Living Donor Liver Transplantation
Background: The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown.
Method: A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed.
Results: At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P<0.05). None had side effects or hepatitis B infection during the study period.
Conclusions: In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG.
The presence of antibody to the hepatitis B core antigen (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) in the serum indicates past exposure to the hepatitis B virus (HBV). The current shortage of donors has forced the transplant community to utilize livers from anti-HBc-positive donors, especially for immune recipients (i.e. presence of anti-HBc or anti-HBs) or HBsAg-positive patients who will receive polyclonal hepatitis B immunoglobulin (HBIG) with or without lamivudine (LAM), as well as for critically ill patients. In one large study, HBV infection developed in 18 out of 23 (78%) recipients of anti-HBc-positive donor livers without prophylaxis, compared with only three of 651 (0.5%) recipients of anti-HBc-negative donor livers. Another study also revealed that almost all HBV-naïve recipients who had received grafts from anti-HBc-positive living donors developed evidence of de novo HBV infection without prophylaxis. Moreover, despite the presumed resolution of HBV infection, polymerase chain reaction (PCR) studies revealed that minute HBV DNA can be detected in anti-HBc-positive donor livers. These facts suggest that latent HBV in a liver from an anti-HBc-positive donor can be reactivated under immunosuppressive circumstances in a recipient. Based on these findings, consensus has been reached that the use of anti-HBc-positive donor livers carry an extremely high risk of developing de novo hepatitis B infections and require post-transplant prophylaxis using HBIG and/or LAM, if such livers are transplanted to HBV-naïve patients. However, a life-long requirement of highly expensive HBIG has been a matter of debate and a cost-effective substitution to HBIG prophylaxis has long been awaited.
Living donor liver transplantation (LDLT) has evolved to be an established modality for patients with end-stage liver disease as an alternative to deceased donor liver transplantation. In the setting of LDLT, the number of donor tends to be limited and the use of liver grafts from an anti-HBc-positive donor may often be the only option. Therefore, the development of an alternative strategy against hepatitis B infections without the use of expensive HBIG is a critical issue in such high prevalent counties to effectively utilize such donors.
Active immunization using recombinant HBV antigen is a safe and very effective modality to obtain a protective anti-HBs titre for the healthy population (90-95%), but much less so in immunosuppressed patients such as HIV-positive-persons, kidney and liver transplant recipients, and oncology patients. Regarding the effect of HBV vaccination after liver transplantation, mixed results have been reported. Nonetheless, if HBV vaccination is potentially effective, it can be an attractive alternative to expensive HBIG.
Therefore, we undertook a prospective study of HBV vaccination in patients who had undergone LDLT using grafts from anti-HBc-positive donors or who had undergone LDLT for fulminant hepatitis B, all had been on HBIG and LAM prophylaxis before the study.
Abstract and Introduction
Abstract
Background: The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown.
Method: A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed.
Results: At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P<0.05). None had side effects or hepatitis B infection during the study period.
Conclusions: In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG.
Introduction
The presence of antibody to the hepatitis B core antigen (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) in the serum indicates past exposure to the hepatitis B virus (HBV). The current shortage of donors has forced the transplant community to utilize livers from anti-HBc-positive donors, especially for immune recipients (i.e. presence of anti-HBc or anti-HBs) or HBsAg-positive patients who will receive polyclonal hepatitis B immunoglobulin (HBIG) with or without lamivudine (LAM), as well as for critically ill patients. In one large study, HBV infection developed in 18 out of 23 (78%) recipients of anti-HBc-positive donor livers without prophylaxis, compared with only three of 651 (0.5%) recipients of anti-HBc-negative donor livers. Another study also revealed that almost all HBV-naïve recipients who had received grafts from anti-HBc-positive living donors developed evidence of de novo HBV infection without prophylaxis. Moreover, despite the presumed resolution of HBV infection, polymerase chain reaction (PCR) studies revealed that minute HBV DNA can be detected in anti-HBc-positive donor livers. These facts suggest that latent HBV in a liver from an anti-HBc-positive donor can be reactivated under immunosuppressive circumstances in a recipient. Based on these findings, consensus has been reached that the use of anti-HBc-positive donor livers carry an extremely high risk of developing de novo hepatitis B infections and require post-transplant prophylaxis using HBIG and/or LAM, if such livers are transplanted to HBV-naïve patients. However, a life-long requirement of highly expensive HBIG has been a matter of debate and a cost-effective substitution to HBIG prophylaxis has long been awaited.
Living donor liver transplantation (LDLT) has evolved to be an established modality for patients with end-stage liver disease as an alternative to deceased donor liver transplantation. In the setting of LDLT, the number of donor tends to be limited and the use of liver grafts from an anti-HBc-positive donor may often be the only option. Therefore, the development of an alternative strategy against hepatitis B infections without the use of expensive HBIG is a critical issue in such high prevalent counties to effectively utilize such donors.
Active immunization using recombinant HBV antigen is a safe and very effective modality to obtain a protective anti-HBs titre for the healthy population (90-95%), but much less so in immunosuppressed patients such as HIV-positive-persons, kidney and liver transplant recipients, and oncology patients. Regarding the effect of HBV vaccination after liver transplantation, mixed results have been reported. Nonetheless, if HBV vaccination is potentially effective, it can be an attractive alternative to expensive HBIG.
Therefore, we undertook a prospective study of HBV vaccination in patients who had undergone LDLT using grafts from anti-HBc-positive donors or who had undergone LDLT for fulminant hepatitis B, all had been on HBIG and LAM prophylaxis before the study.
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