Use of Hepatitis B Core Antibody–Positive Liver Allograft in Hepatitis
C Virus–Positive and –Negative Recipients With Use of Short Course
of Hepatitis B Immunoglobulin and Lamivudine
A. Jain, M. Orloff, P. Abt, R. Kashyap, R. Mohanka, K. Lansing, M. Kelley, and A. Bozorgzadeh
antibody (HBcAb)–positive [HBcAb(?)] liver allografts are being used for liver trans-
plantation (LTx) in patients who are HBcab-negative [HBsAb(?)]. This study was aimed
at assessing outcomes for hepatitis C virus (HCV)-positive [HCV(?)] and HCV-negative
[HCV(?)] patients who received HBcAb(?) liver grafts from deceased donors and also
received a short course of hepatitis B immunoglobulin (HBIg) with long-term lamivudine
therapy after LTx.
Materials and methods.
From February 1995 through February 2003, 28 patients (mean
age 53.8 ? 10.2 years, 19 men and nine women, 16 HCV[?]; 12 HCV[?]) received
HbcAb(?) liver allografts. All recipients received a short course of HBIg prophylaxis
(10,000 units/day for 4 days) and long-term lamivudine 100 mg/d after LTx in addition to
a tacrolimus-based immunosuppressive regimen.
Seven (25%) of the 28 recipients died during follow-up and three recipients
required retransplantation. Three recipients (10.7%) developed HBV infection during
follow-up, one of whom died 36 months after LTx and the other two had YMDD mutant
HBV. The overall 6-year actuarial patient survival after transplantation was 74.4% and
those for HCV(?) and HCV(?) recipients were 81.3% and 66.6%, respectively (P ? .46).
The overall 6-year actuarial graft survival was 63.9% and those for HCV(?) and HCV(?)
recipients were 68.8% and 57.1%, respectively (P ? .6).
We conclude that HBcAb(?) liver grafts can be used for both HCV(?)
patients and HCV(?) patients who are critically ill, have early hepatocellular carcinoma,
or have been exposed to HBV in the past. A short course of HBIg-lamivudine combination
therapy provides effective prophylaxis against HBV infection in 89% of recipients of
With the shortage of donor organs, increasing number of hepatitis B core
patients who have been vaccinated against hepatitis B virus
(HBV) and have developed hepatitis B surface antibodies
(HBsAb) and in patients who are HBV carriers HBsAg(?).
The HBV carriers who undergo a liver transplant receive a
long course of anti-HBV immunoglobulin (HBIg) after
With the shortage of deceased donor organs, increasing
numbers of HBcAb(?) liver allografts are being used for
liver transplantation (LTx) in patients who are HBsAb(?).
The risk of transmitting HBV infection in these cases is well
IVER GRAFTS from donors who are positive for
hepatitis B core antibody (HBcAb) are mainly used in
documented.1–3However, this risk is considered acceptable
for patients who are critically ill or have stage I/II hepato-
cellular carcinoma (HCC). The numbers of patients with
hepatitis C virus (HCV) infection receiving liver transplants
is increasing in the United States. To date, no study has
From the Department of Surgery, Division of Transplantation,
Strong Memorial Hospital, Rochester, New York, USA.
Address reprint requests to: Ashokkumar Jain, MD, University
of Rochester Medical Centre, Department of Surgery, Division of
Transplantation, Box SURG 601 Elmwood Avenue, Rochester,
NY 14642. E-mail: firstname.lastname@example.org
© 2005 by Elsevier Inc. All rights reserved.
360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter
Transplantation Proceedings, 37, 3187–3189 (2005) 3187
examined outcomes for recipients of HBcAb(?) livers from
deceased donors who complete a short course of HBIg and
take long-term lamivudine after LTx.
Our aim in this study was to assess outcome for HCV(?)
and HCV(?) patients who received HBcAb(?) liver grafts
from deceased donors and also received a short course of
HBIg with long-term lamivudine therapy after LTx.
PATIENTS AND METHODS
From February 1995 through February 2003, 28 patients at our
institution received liver allografts from HBcAb(?) deceased
donors. The recipients were 19 men and nine women of mean age
53.8 ? 10.2 years. The primary reason for use of HBcAb(?) donor
grafts were as follows: critically ill recipient (n ? 11), HCC stage
I/II (n ? 6), and HBcAb(?) recipient (n ? 11). Some of these
patients had more than one of these conditions. Polymerase chain
reaction identified 16 of the patients as HCV-RNA(?) and 12 as
HCV-RNA(?). All recipients were followed until November 2004
(mean follow-up period 36.4 ? 19.0 months). All donors in the
United States are routinely screened for HBV infection using
hepatitis B surface antigen (HBsAg), HBsAb, and HBcAb. The
present study focused on liver transplants with a HBcAb(?) liver
allograft alone at our center during the study period. These donors
were further screened for HBcAb immunoglobulin (Ig) and HB-
cAb IgM and all grafts that were HBsAg(?) or HBcAb IgM(?)
were excluded from transplantation. All serology was done using
one-step enzyme immunoassay. The mean donor age for the study
group was 53.6 ? 15.8 years.
Each of the 28 patients received a short course of intravenous
HBIg prophylaxis (10,000 units daily for 4 days) and long-term
lamivudine 100 mg/day after LTx. After transplantation, all pa-
tients were placed on an immunosuppression protocol of tacroli-
mus, mycophenolate mofetil, and steroid, as previously described.4
Data are presented as mean ? standard deviation. Actuarial
survival was calculated using the Kaplan-Meier formula, and
differences in survival for the HCV(?) and HCV(?) groups were
compared using the log-rank formula. The software package SPSS
for Windows version 11.5 was used for all calculations.
Overall Patient and Graft Survival
Seven (25%) of the 28 recipients died during follow-up. The
causes of death were sepsis (n ? 3), cardiac failure (n ? 2),
recurrent HBV infection (n ? 1), and recurrent metastatic
HCC (n ? 1). The actuarial patient survival at 6 years after
transplantation was 74.4% (Fig 1A). Three patients lost
their grafts due to hepatic artery thrombosis and had to be
retransplanted. The actuarial graft survival at 6 years was
63.9% (Fig 1A).
Overall Incidence of HBV Infection
Three patients (10.7%) became HBV-DNA-positive during
follow-up. One of these recipients died of liver failure from
HBV infection 36 months after LTx. HBV-DNA results
from the other two patients revealed YMDD mutation.
Both these recipients are currently being treated with
Results for the HCV(?) and HCV(?) Recipients
As noted, 12 patients were HCV(?) and 16 were HCV(?).
The primary reasons HBcAb(?) grafts were used in the 12
HCV(?) cases were as follows: critically ill patient (n ? 2),
presence of HCC (n ? 2), or HBcAb(?) (n ? 8).
Four (33.3%) of the HCV(?) patients died at 7.5, 7.7,
19.1, and 23.2 months posttransplantation. The causes of
death were cardiac arrest after recurrent HCV (n ? 1),
recurrent HCC (n ? 1), cardiac arrest (n ? 1), and sepsis
due to recurrent cholangitis secondary to intrahepatic bile
duct stricture (n ? 1), respectively. The 6-year actuarial
patient survivals for HCV(?) and HCV(?) groups were
66.6% and 81.3%, respectively (P ? .46; Fig 1B).
One of the HCV(?) recipients had to be retransplanted
after he developed hepatic artery thrombosis after 9 post-
operative days. The 6-year actuarial graft survivals for
HCV(?) and HCV(?) recipients were 57.8% and 68.8%,
respectively (P ? .06; Fig 1C).
None of the HCV(?) recipients developed HBV infec-
tion during the study period; all three recipients who
developed HBV infection were HCV(?).
The risk of transmitting HBV or developing it after LTx
involving an HBcAb(?) donor is well documented. Without
prophylaxis, the reported infection rates are higher than
cAb(?) donor transplants. (A) Overall patient and graft survival.
(B) Patient survival for the HCV(?) and HCV(?) recipient groups.
(C) Graft survival for the HCV(?) and HCV(?) recipient groups.
Recipient patient and graft survival statistics for HB-
3188 JAIN, ORLOFF, ABT ET AL
80%. The problem may even be greater in regions where Download full-text
the prevalence of HBV is very high.5Lamivudine therapy
with or without HBIg has been suggested as prophylaxis in
such cases.1,6However, the duration of treatment required
has not been evaluated.3,7A recent survey showed incon-
sistency among the prophylactic regimens in use by different
centers.8We felt that our protocol of using a short course of
HBIg with long-term lamivudine may provide a satisfactory
balanced approach to this problem.
We observed lower patient and graft survivals with use of
HBcAb(?) in HCV(?) recipients compared to HCV(?),
but the differences were not statistically significant and
these results were due to patient characteristics rather than
donor characteristics, since none of the HCV(?) individu-
als developed HBsAg positivity.
Our results indicate that a short course of HBIg-
lamivudine combination therapy provides effective pro-
phylaxis against HBV infection in 89% of recipients of
HBcAb(?) grafts. Nonetheless, routine periodic HBV
screening of HBcAb(?) graft recipients is mandatory for
early detection of HBV infection and identify known viral
In conclusion, we conclude that HBcAb(?) liver grafts
can be used for both HCV(?) patients and HCV(?)
patients who are critically ill, have early HCC, or have been
exposed to HBV in the past. A short course of HBIg-
lamivudine combination therapy provides effective pro-
phylaxis against HBV infection in 89% of recipients of
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antibody to hepatitis B core antigen. The National Institute of
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Database. Gastroenterology 113:1668, 1997
2. Dodson SF, Issa S, Araya V, et al. Infectivity of hepatic
allografts with antibodies to hepatitis B virus. Transplantation
3. Dodson SF, Bonham CA, Geller DA, et al: Prevention of de
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anti-HBc positive donors. Transplantation 68:1058, 1999
4. Bozorgzadeh A, Jain A, Ryan C, et al: Impact of hepatitis C
viral infection in primary cadaveric liver allograft versus primary
living-donor allograft in 100 consecutive liver transplant recipients
receiving tacrolimus. Transplantation 77:1066, 2004
5. Al-Sebayel MI, Khalaf HA, Ramirez CG: The prevalence of
hepatitis B core antibody positivity in donors for liver transplanta-
tion in Saudi Arabia. Saudi Med J 23:298, 2002
6. Douglas DD, Rakela J, Wright TL, et al: The clinical course
of transplantation-associated de novo hepatitis B infection in the
liver transplant recipient. Liver Transpl Surg 3:105, 1997
7. Dodson SF: Prevention of de novo hepatitis B infection after
liver transplantation with allografts from hepatitis B core antibody
positive donors. Clin Transplant 14(suppl 2):20, 2000
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