Hepatitis B immunoglobulin discontinuation followed by hepatitis B virus vaccination: A new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation

Abstract

It is widely agreed that hepatitis B virus immunoglobulinSeveral reports have clearly shown that liver transplantation in patients with hepatitis B virus (HBV) infection-as defined by positivity for hepatitis B surface antigen (HBsAg)-is associated with a high rate of recurrence of HBV infection after transplantation, resulting in severe graft disease in most cases and in a significant decrease in both graft and patient survival. [1][2][3][4] It is widely accepted that the risk of HBV recurrence after liver transplantation is directly proportional to the level of viral replication before transplantation, with those recipients seropositive for HBeAg and HBV DNA by hybridization technique having the highest rate of recurrence after transplantation, irrespective of the type of liver disease. 2,4 Many prophylactic strategies have been proposed to prevent HBV infection of the graft, but only long-term passive immunoprophylaxis with HBV-specific immunoglobulin (HBIG) has obtained a significant reduction in the risk of HBV graft infection and in both graft and patient mortality after liver transplantation. [4][5][6][7] The presence of serum HBV DNA before transplantation is, however, a major predictor of lack of response to this prophylactic regimen.In light of these evidences, the European Concerted Action on Viral Hepatitis (EUROHEP) recommended in 1994 to refrain from transplanting chronic HBV carriers found to be positive for either hepatitis B e antigen (HBeAg) or HBV DNA by direct hybridization. Moreover, the rest of the recipients with HBV-related disease should receive HBIG immunoprophylaxis to maintain anti-HBs levels above 100 IU/L for at least 12 months after transplantation. 6 Currently, the beneficial effect of long-term HBIG administration has become widely accepted; still no consensus has been reached regarding the optimal duration of HBIG treatment. The rate of HBV graft infection recurrence 12 months after liver transplantation seems to be much decreased but it can still undoubtedly occur. 4,6,[8][9][10] Moreover the finding of HBV DNA in peripheral mononuclear blood beyond 12 months of effective HBIG prophylaxis argues in favor of a potentially indefinite risk of graft infection. 11-13 As a consequence, most liver transplant centers are currently administering HBIG on a life-long basis. Because HBIG use is highly expensive, an alternative strategy aiming at the discontinuation of HBIG prophylaxis during the second year of treatment would be an important cost-effective measure. We present here an assessment of the efficacy of a new prophylactic strategy consisting of the discontinuation of HBIG administration followed by active immunization with HBV vaccination in patients transplanted for HBVrelated liver diseases. PATIENTS AND METHODSPatients. Between July 1990 and April 1996, 36 HBsAg-positive recipients were submitted to liver transplantation at the Hospital Abbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B virus surface antigen; HBIG, hepatitis B virus immunoglobulin; HBeAg, hepatitis B vi...

Development of antibody to hepatitis B surface antigen after liver transplantation for chronic hepatitis B

“…Therefore, the spontaneous development of anti-HBs is most unexpected and has not been reported previously in other series of patients receiving lamivudine prophylaxis 5,7 or in whom HBIg prophylaxis was discontinued after long-term administration. [2][3][4]20 Our study shows that this phenomenon is not related to any recipient factors, such as the pretransplantation HBV replication status or immunosuppression, but is strongly related to the HBV immunity status of the donor. Among the 21 patients with anti-HBs production, all except 2 had received liver grafts from anti-HBs-positive donors, and the remaining 2 donors had an anti-HBs titer just below 10 mIU/mL.…”

“…It may be worthwhile to offer vaccination to boost the anti-HBs level, but the efficacy of hepatitis B vaccination in patients after liver transplantation for chronic hepatitis B is controversial. 20,35 The antiHBs response may simply indicate the transient presence of anti-HBs producing B lymphocytes of graft origin in the recipient. Because the lymphocytes do not engraft and have a finite life span, 29 the antibody titer declines as a result of the disappearance of these cells, and the effectiveness of vaccination may be questionable.…”

Vaccination for hepatitis B after transplantation: A realistic goal?

“…The response in this series to a commercially available recombinant HBsAg vaccine was poor and in clear distinction to a recent experience from Barcelona. 4 The patient populations, methodologies, and definitions were somewhat different.In the series from Barcelona, 17 good risk patients (nonreplicative before transplantation, HBIG for at least 18 months without evidence of allograft HBV infection, and on low immunosuppressive doses) were chosen for vaccination. Six patients had received transplantation for HBV-induced fulminant hepatic failure and 11 for HBV-related cirrhosis.…”

“…The response in this series to a commercially available recombinant HBsAg vaccine was poor and in clear distinction to a recent experience from Barcelona. 4 The patient populations, methodologies, and definitions were somewhat different.…”

Posttransplantation prevention and treatment of recurrent hepatitis B

“…The administration of hepatitis B vaccine to induce active immunity before consideration of discontinuing HBIG therapy has been used in small numbers of patients with limited success. 6 The long-term benefit of this approach in the prevention of hepatitis B recurrence is unproven.…”