Terrault_edit.qxp 4/10/07 11:42 am Page 45
HepaGam B After Liver Transplant in Patients with Hepatitis B Virus
and one patient required adjustment of the dosing regimen due to an
Figure 2: Time to Recurrence of Hepatitis B Virus Infection
adverse event. No laboratory abnormalities observed on study were
considered to be related to study drug.
Survival distribution function
1.00
Discussion
Although the use of prophylactic therapies including HBIG and antiviral drugs
has resulted in excellent outcomes for patients with hepatitis B-related liver
0.75
Historical control (n=12)
failure, these therapies were not licensed in North America for the prevention
HepaGam B (n=20)
of HBV recurrence following LT until recently. This study reports the efficacy of
0.50
high-dose long-term HBIG in preventing HBV re-infection in HBsAg-positive/
HBeAg-negative patients undergoing LT. The primary efficacy end-point
results are supported by time to recurrence data, survival rates, anti-HBs serum 0.25
concentrations, and biochemical markers of liver inflammation. HepaGam B is
the first HBV immunoglobulin product to be approved for this indication. The
recurrence rate observed with non-replicating patients treated with high-dose
0.00
0 50 100 150 200 250 300 350 400 450
long-term HBIG monotherapy in this study is similar to that for patients
Time (days)
receiving combination treatment with HBIG plus antiviral therapy.
14–17
This
contrasts with the higher rates of recurrence observed with antiviral
HBIG = hepatitis B immunoglobulin.
monotherapy.
18–20
These results support the current central role of HBIG in the
management of HBV-infected transplant recipients.
Figure 3: Proportion of Patients with One-year Survival Following
Liver Transplantation
Various routes of administration (e.g. intramuscular versus intravenous) and
dosing regimens of HBIG have been studied.
4,21
We chose to evaluate a
Proportion of patients (%), 95% CI p=0.0118
regularly scheduled regimen of intravenously administered high-dose, long- 100
95.0
term HBIG based on previously published reports.
2,6,12
Intravenous infusions of 90
high-dose HBIG (i.e. 10,000IU/dose) have been shown to achieve trough anti-
80
HBs concentrations of ≥500IU/l. The use of regularly scheduled doses
70
eliminates the significant variability in anti-HBs titers that can occur when anti-
60
HBs trough concentrations are used to determine the frequency of
42.9
50
administration.
12
Setting the trough anti-HBs concentrations at ≥500IU/l has
40
been shown to prevent 90–100% of post-LT HBV re-infections in patients
receiving HBIG monotherapy.
4,6,12,13
A pre-determined schedule of visits for
30
HBIG administration enabled excellent patient adherence to treatment.
20
10
Of the 177 adverse events reported in this study, only three (tremor, 0
HBIG Historical control
hypotension, and fever) were determined to be related to study drug and
(n=20) (n=14)
resolved without sequelae. None of these events were serious nor recurrent.
In conclusion, this study shows that high-dose, long-term HBIG (HepaGam
CI = confidence interval; HBIG = hepatitis B immunoglobulin.
B) monotherapy is a well-tolerated and highly effective form of prophylaxis
in non-replicating HBsAg-positive patients. With the approval of this agent,
the transplant community now has its first approved form of antibody Acknowledgements
prophylaxis for HBV-infected patients. Future studies will determine the role The authors acknowledge Scientific Connexions, Newtown, Pennsylvania,
of the agent in conjunction with antiviral therapy. ■ for writing assistance on this manuscript.
1. Schreibman IR, Schiff ER, Ann Clin Microbiol Antimicrob, 2006;5:8 8. Seehofer D, Berg T, Transplantation, 2005;80(Suppl. 1):S120-S124. 13. Vargas HE, Dodson FS, Rakela J, Liver Transpl, 2002;8:2–9.
[coi: 10.1186/1476-0711-5-8]. Available at: http://www.ann- 9. Hepatitis B Immune Globulin Intravenous (Human). Product approval 14. McCaughan GW, Spencer J, Koorey D, et al., Liver Transpl Surg,
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US GASTROENTEROLOGY REVIEW 2007 45
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