Vaccination for hepatitis B after transplantation: A realistic goal?

Abstract

L iver transplantation for hepatitis B has become remarkably successful over the past decade. This success has been predicated upon effective therapy to prevent clinical infection of the transplanted liver by hepatitis B virus (HBV). The cornerstone of therapy to prevent HBV infection in the transplanted liver has been the use of hepatitis B immune globulin (HBIG). With the availability of effective antiviral therapy (especially lamivudine with others soon to be available), the repertoire for HBV containment is increasing. There are significant shortcomings to longterm HBIG and lamivudine, not least of which has been cost and drug resistance. The prospect of inducing active immunity against HBV, without the need for additional treatment for the virus, was examined in the article by Angelico et al. in this issue of HEPATOL-OGY. 1 The immunization regimen was based on the knowledge that HBV vaccination in cirrhotic patients and non-HBV liver transplant recipients results in a low rate of hepatitis B surface antibody (anti-HBs) seroconversion. 2,3 The study included 17 virologically negative (hepatitis B surface antigen [HBsAg] and HBV-DNA negative by polymerase chain reaction on at least two consecutive assays) liver transplant recipients on cyclosporine monotherapy, who had undergone transplantation for HBV-related cirrhosis 25 to 85 months previously. Fifteen recipients were men. All patients were HBV-DNA negative (by hybridization assay) at the time of transplantation and 41% were hepatitis D antibody positive. HBIG monotherapy had been given to all patients on a monthly (typically about 5,000 IU) basis until entry into the study. Four weeks after the last dose of HBIG, the patients were started on lamivudine. The anti-HBs titers were followed until they were less than 10 IU/L, a median of 4.5 months after the last HBIG dose. The first course of vaccination used 40 g (double dose) recombinant HBsAg (Recombivax) given intramuscularly at 0, 1, and 2 months. Early response was defined as an anti-HBs titer greater than 100 IU/L at 3 months. One individual (5.9%) developed an early response with an anti-HBs titer of 687 IU/L at month 3 and one developed an anti-HBs titer of 20 IU/L. The 16 nonresponders were given a second course of vaccination: 10 g of recombinant HBsAg intradermally every 15 days for 3 months (6 doses). No additional patient developed an anti-HBs titer Ͼ100 IU/L, so all 16 were given a third vaccination series exactly the same as the first (40 g intramuscularly monthly for 3 doses). One patient responded at month 10 with an anti-HBs titer of 253 IU/L. In aggregate, 2 of 17 (12%) developed an anti-HBs titer greater than 100 IU/L and 3 more (18%) had a titer greater than 10 IU/L after the 3 vaccination courses. Per protocol, the 15 nonresponders resumed intravenous HBIG. Of two responders, one stopped lamivudine and one continued because the anti-HBs response was not durable. No patient developed HBV reinfection. The response in this series to a commercially available recombinant HBsAg vaccine was ...

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“…On the other hand, one of our recent nonresponders vaccinated while receiving lamivudine, developed positive serum hepatitis B surface antigen and HBV DNA 9 months after the failure of vaccination despite the uninterrupted administration of oral lamivudine. Although we currently have no data regarding lamivudine resistance in this patient, the case appears to be similar to the one described by Pruett 3 and suggests that, at least in nonresponders to HBV vaccination, hepatitis B immune globulin may be a safer prophylactic regimen than lamivudine.…”

“…Traditionally, the threshold for considering a therapy cost effective has been $50,000 per life year saved or quality adjusted life year saved. 3 Since no incremental increase in life expectancy was demonstrated and quality of life measures were the same in both groups, whether the additional costs of TIPS are justified for the purported benefits is a subjective one. Consideration should be based on the availability of local resources and competing therapies that may deliver health care at a more cost-effective rate.…”

One-year vaccination against hepatitis B virus with a MPL-vaccine in liver transplant patients for HBV-related cirrhosis

“…The rationale for combining vaccine with HBIg in phase I is supported by the hypothesis that the formation of HBIg/HBsAg complexes might increase vaccine immunogenicity [44,45]. The need to continue vaccination after HBIg withdrawal in phase II was considered to be crucial to strengthen the response to vaccination and to exclude the possibility of detecting spurious anti‐HBs titers.…”

Mechanisms of hepatitis B virus graft reinfection and graft damage after liver transplantation

“…The Barcelona group [65] published a favourable study for this approach. However, since these initial report new studies indicated that this intriguing concept might be not as easy as originally thought to bring into the clinic [66,67]. Especially the study by Angelico et al [66] suggested that there is a strong variation in the immune response after HBsAg vaccination in patients after liver transplantation.…”