Beth Israel Deaconess Medical Center
Transplant Manual
Title: HBV - Immunoprophylaxis for Liver Transplant Recipients
Purpose: To outline process for clinical management of liver transplant recipients
Policy Statement:
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The introduction of Hepatitis B immunoglobulin for prophylaxis
against graft re-infection following transplantation for HBV has
increased the overall survival rate to greater than 80% for 1 year
and 65% for 3 years.
The high rate of re-infection after liver transplantation is probably
due to the enhanced virus replication resulting from
immunosuppression or direct stimulatory effect of steroid therapy on
the steroid responsive enhancer region of the HBV genome.
Factors associated with a lower rate of re-infection include:
a)
pretransplant HBeAg negative assay
b)
negative HBV DNA assay by non PCR technique
c)
fulminant HBV
d)
co-existent D virus infection
Passive immunoprophylaxis with HBig is based upon the rationale
that HBs antibodies will bind to and neutralize circulating virus.
Many patients become re-infected if HBig is stopped, so long term
passive immunoprophylaxis is required if HBig is used as a sole
agent to prevent re-infection.
Recurrence of HBV infection of the graft in patients on HBig
suggests:
a)
inadequate dosing schedule;
b)
the emergence of viral escape mutants which are typically
mutations in the “a” determinant of the HBsAg. The
emergence of these viral escape mutants appears to be
temporarily related and suggests that more effective anti-viral
prophylaxis is required.
The presence of replicating virus in the serum prior to
transplantation, as evidenced by a positive HBeAg assay or high
titer HBV DNA, is associated with a higher re-infection rate despite
HBig. To combat this problem, active antiviral therapy has been
instituted in most transplant centers to reduce viral replication.
Lamivudine, adefovir, entecavir, and telbivudine are all FDAapproved for treatment of HBV. It is orally administered and is
tolerated well. It has also been associated with the development of
viral escape mutation (typically HMDD mutants) in the polymerase
region of the viral genome.
To prevent recurrence, a combination of lamivudine begun preoperatively and HBig begun peri-operatively has been adopted as
standard practice. In one study there was no recurrence of HBV in
60 patients treated with this combination followed for a mean of 449
days.
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Protocol for transplantation of HBV positive recipients and recipients of
HBcAb+ livers:
HBV non-replicators (i.e., HBsAg positive, negative HBeAg, positive HBeAb and
negative HBV DNA by non PCR techniques [<5 pg/ml] or <1x105 copies/ ml by
PCR)
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Hepatitis B immunoglobin (HBig) 10,000 units IV during the anhepatic
stage of the transplant.
5000 units IV per day for the first 5 days post-transplant to ensure (a) antiHBs >500 u/L and (b) absence of HBsAg.
Quantitative HBsAb and HBsAg need to be measured daily and be in the
lab by 8 AM.
Commence nucleoside or nucleotide analogue that patient was on pretransplant on post-operative day 0.
Hepatitis B Immunoglobulin 5.0 ml IM (>1560 units) (Nabi HBig) on days 7,
14, 21 and 28 to maintain level of anti-HBs >500 u/L. If INR >1.4, then
administer 5000 units IV until INR <1.4.
Anti-HBs titers will be checked on post-operative days 7, 14, 21 and 28
prior to administration.
Maintain the following doses and titers for the first year:
Anti-HBs titers
Hepatitis B immunoglobulin dose
<500 IU
5.0 ml IM (>1560 IU)
>500 IU
no dose given
Maintain the following doses and titers after 12 months:
Anti-HBs titers
Hepatitis B immunoglobulin dose
<10 IU
5.0 ml IM (>1560 IU)
>10 IU
no dose given
HBV replicators (i.e., HBsAg positive, positive HBeAg, negative HBeAb and
positive HBV DNA by non PCR (>5pg/ml) or >1x105 copies/ml by PCR)
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Lamivudine, adefovir, entecavir or telbifudine commenced at standard dose
at preference of hepatologist.*
Treatment with nucleoside/nucleotide analogue should be dictated by HBV
genotype.
Recheck HBV DNA to ensure HBV DNA <5 pg/ml by bDNA or <1x105
copies/ml levels after 6 weeks of therapy.
Continue nucleoside or nucleotide analogue adjusted for renal function
following transplantation, starting on post-operative day 0.
Hepatitis B Immunoglobulin (HBig) 10,000 units IV at the anhepatic stage
of the transplant.
5000 units IV per day for the first 5 days post-transplant to ensure (a) antiHBs >500 u/L and (b) absence of HBsAg.
Quantitative HBsAb and HBsAg need to be measured daily and be in the
lab by 8 AM.
Hepatitis B Immunoglobulin 5.0 ml IM (>1560 IU) on days 7, 14, 21 and 28
to maintain level of anti-HBs >500;u/L. If INR >1.4, then administer 5000
units IV until INR <1.4.
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Anti-HBs titers will be checked on post-operative days 7, 14, 21 and 28
prior to administration, then every 2 weeks for 3 months and every month
thereafter.
Maintain the following doses and titers for the first year:
Anti-HBs titers
Hepatitis B Immunoglobulin dose
<500 IU
5.0ml IM (>1560 IU)
>500 IU
no dose given
Maintain the following doses and titers after 12 months:
Anti-HBs titers
Hepatitis B Immunoglobulin dose
<500 IU
5.0ml IM (>1560 IU)
>500 IU
no dose given
Recipient of HBcAb+ donors to HBsAb- non-immune recipients
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Hepatitis B Immunoglobulin (HBig) 10,000 units IV during the anhepatic
stage of the transplant; 5000 units IV per day for the first 5 days posttransplant to ensure (a) anti-HBs >300 u/L and (b) absence of HBsAg.
Commence lamivudine 100 mg per day* on post-operative day 0.
Contact the New England Organ Bank and obtain the results of the HBV
DNA on the donor.
Hepatitis B Immunoglobulin 5.0 ml IM (>1560 IU) on days 7, 14, 21 and 28
to maintain level of anti-HBs >300 u/L. If PT >14 seconds or low platelets,
then administer 10,000 IU IV monthly until IM administration safe.
Quantitative HBsAb and HBsAg need to be measured daily and be in the
lab by 8 AM.
Anti-HBs titers will be checked on post-operative days 7, 14, 21 and 28
prior to administration and then every 2 weeks for 3 months.
Maintain the following doses and titers for the first 3 months:
Anti-HBs titers
Hepatitis B Immunoglobulin dose
<500 IU
5.0ml IM (>1560 IU)
>500 IU
no dose given
Continue lamivudine 100mg po q day indefinitely.
Transplantation of HBcAb+ liver into HBsAb+ recipient
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An HBsAb test will be checked on patient’s admission at the time of
transplant.
If the most recent HBsAb positive result available for review is greater than
6 months, then patient will receive HBig 10,000 units IV during the
anhepatic phase of the transplant.
If HBsAb result taken at admission is positive, no further HBig will be
administered.
If HBsAb result taken at admission is negative, HBig will be administered
daily at 5000 units IV per day for 5 days.
HBig will be administered at a dose of 1560 units by IM injection on days 7,
14, 21, and 28 and monthly for 3 months to keep HBsAb titer > 450.
Lamivudine will start on post-operative day 0 at a dose of 100 mg/day and
continue indefinitely.
*Nucleoside or nucleotide analogues are renally excreted and need to be dosed
according to renal function.
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Vice President Sponsor:
Approved by:
x Liver Selection Committee
Requestor Name:
Original Date Approved:
Next Review Date:
Revised:
Dianne Anderson, Sr. VP PCS
Douglas W. Hanto, MD, PhD and Michael Curry, MD
Co-Chairs
Michael Curry, M.D.
3/05
1/08
1/07
Eliminated:
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