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Hepatitis
HepaGam B After Liver Transplant in Patients with Hepatitis B Virus
a report by
Norah A Terrault,
1
Murat Kilic,
2
Sedat Karademir,
3
Zeki Karasu,
2
Ibrahim Astarcioglu,
3
Maurice Genereux,
4
Jitendra Dixit,
4
Christine Hall
4
and Chris Sinclair
4
1. University of California, San Francisco; 2. Ege University Medical School, Izmir; 3. Dokuz Eylul School of Medicine, Izmir; 4. Cangene Corporation, Winnipeg
Orthotopic liver transplantation (LT) is the definitive treatment for cirrhosis following LT in non-replicating patients compared with a matched
and fulminant liver failure due to hepatitis B virus (HBV) infection.
1
However, population of untreated historical controls.
as recently as 15 years ago HBV infection was a relative contraindication for
LT because of high rates (78%) of HBV re-infection in the months following Methods
transplantation.
2,3
The factor most predictive of risk for post-transplant
re-infection is the presence of high levels of HBV DNA at the time of LT (i.e. Study Design
HBV DNA-positive—namely ~20,000IU/ml or higher—or hepatitis B ‘e’ This was a multicenter, open-label, superiority study of the human HBIG
antigen (HBeAg)-positive).
4
The evolution of effective prophylactic strategies (HepaGam B) in the prevention of hepatitis B re-infection in hepatitis B
over the past 15 years has dramatically improved survival rates, making LT a surface antigen (HBsAg)-positive/HBeAg-negative patients undergoing LT
therapeutic option for patients with hepatitis B-related liver disease.
5
compared with untreated historical controls. The prospective treatment arm
of the study was conducted between April 2004 and January 2007 at two
Hepatitis B immunoglobulin (HBIG) was the first therapy shown to reduce the sites in Turkey and one site in North America. Data for the historical controls
risk of HBV re-infection in LT patients. The use of high-dose, long-term HBIG were collected from sites in North America. The study consisted of six phases:
reduced HBV re-infection rates to 17–35% for patients with actively
replicating HBV pre-LT and to 0–17% among non-replicating patients.
6,7
• screening within one year of LT;
More recently, pre-transplant administration of antiviral nucleoside analogs— • pre-transplant baseline assessment within 72 hours of LT;
followed by combination treatment with HBIG plus nucleoside analogs after • anhepatic phase on the day of LT;
transplantation—has led to further improved patient outcomes, particularly • acute post-operative phase on days one to seven;
for patients who were HBV replicators before transplant.
1,4,8
Despite the • maintenance phase I during weeks two to 12; and
central role of HBIG in management of HBV patients undergoing LT, use of • maintenance phase II during weeks 13 to 52.
the drug in these patients was not sanctioned by the US Food and Drug
Administration (FDA). However, recently approved was HepaGam B Patient Population
(Cangene Corporation, Winnipeg, Manitoba, Canada), a solvent- and Patients in the active treatment group who were scheduled for LT and met
detergent-treated sterile solution of purified gamma globulin (5% or inclusion criteria were eligible for enrollment. The control group was
50mg/ml) containing greater than 312IU/ml of antibodies to hepatitis B identified by a retrospective chart review and consisted of non-replicating
surface antigen (anti-HBs).
9
patients who underwent LT, but did not receive treatment with any other
form of HBV prophylaxis. Control patients had required data in their charts,
received an adequate course of immunosuppression with a calcineurin
A systematic review and meta-analysis inhibitor such as cyclosporine or tacrolimus, and survived LT without need
of the literature demonstrated that
for re-transplantation for at least 29 days.
high-dose, long-term hepatitis B Neither group received antiviral treatment, including lamivudine, adefovir, or
immunoglobin monotherapy is highly
interferon-alpha2b, within 12 weeks before LT or before re-infection following
LT. Patients not admitted to the treatment group included those with:
effective in preventing hepatitis B virus
recurrence in non-replicating patients.
• known hypersensitivity to blood products;
• a positive test for HIV or hepatitis C virus;
• LT due to fulminant hepatitis B, hepatoma, or multifocal nodes fulfilling
Building on this information, the study compared HBIG monotherapy in Milan criteria
11
at transplant;
non-replicating patients with carefully selected, matched, untreated • multi-organ transplantation, liver re-transplantation except for primary
historical controls, which is an ethical and rational study designed to assess non-function;
the efficacy of HBIG monotherapy in this population. Herein, we report the • a liver graft from an HBsAg- or anti-hepatitis B core antigen-positive
findings of a study designed to evaluate the efficacy of high-dose, long- donor; or
term HBIG—HepaGam B—in preventing HBV re-infection in the year • a known or suspected pre-core or core promoter mutation in HBV genome.
© TOUCH BRIEFINGS 2007
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