C
American Journal of Transplantation 2015; 15: 1162–1172
Wiley Periodicals Inc.
Copyright 2015 The American Society of Transplantation
and the American Society of Transplant Surgeons
doi: 10.1111/ajt.13187
Special Article
Solid Organ Transplantation From Hepatitis B
Virus–Positive Donors: yConsensus Guidelines for
Recipient Management
S. Huprikar1,*, L. Danziger-Isakov2, J. Ahn3,
S. Naugler3, E. Blumberg4, R. K. Avery5,
C. Koval6, E. D. Lease7, A. Pillai8,
K. E. Doucette9, J. Levitsky10, M. I. Morris11,
K. Lu12, J. K. McDermott13, T. Mone14,
J. P. Orlowski15, D. M. Dadhania16, K. Abbott17,
S. Horslen18, B. L. Laskin19, A. Mougdil20,
V. L. Venkat21, K. Korenblat22, V. Kumar23,
P. Grossi24, R. D. Bloom4, K. Brown25,
C. N. Kotton26 and D. Kumar27
1
Icahn School of Medicine at Mount Sinai, New York, NY
Cincinnati Children’s Hospital Medical Center, Cincinnati,
OH
3
Oregon Health Sciences University, Portland, OR
4
Perelman School of Medicine at the University of
Pennsylvania, Philadelphia, PA
5
Johns Hopkins, Baltimore, MD
6
Cleveland Clinic, Cleveland, OH
7
University of Washington, Seattle, WA
8
Emory University Hospital, Atlanta, GA
9
University of Alberta, Edmonton, Alberta, Canada
10
Northwestern University Feinberg School of Medicine,
Chicago, IL
11
University of Miami Miller School of Medicine, Miami,
FL
12
Division of Urology, Department of Surgery, I-Shou
University, Kaohsiung City, Taiwan
13
Spectrum Health, Grand Rapids, MI
14
OneLegacy, Los Angeles, CA
15
LifeShare of Oklahoma, Oklahoma City, OK
16
Cornell University, New York, NY
17
Walter Reed National Military Medical Center,
Bethesda, MD
18
Seattle Children’s Hospital, Seattle, WA
19
The Children’s Hospital of Philadelphia, Philadelphia, PA
20
Children’s National Medical Center, Washington, DC
21
Pediatrics Children’s Hospital of Pittsburgh of UPMC,
Pittsburgh, PA
22
Washington University, St. Louis, MO
23
University of Alabama at Birmingham, Birmingham, AL
24
University of Insubria, Varese, Italy
25
Henry Ford Hospital, Detroit, MI
26
Massachusetts General Hospital, Boston, MA
27
University of Toronto, Toronto, Ontario
Corresponding author: Shirish Huprikar,
[email protected]
2
y
Endorsed by the American Society of Transplantation
and the Canadian Society of Transplantation.
Use of organs from donors testing positive for hepatitis
B virus (HBV) may safely expand the donor pool. The
American Society of Transplantation convened a
multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of
organs from HBV positive donors. Transmission risk is
highest with liver donors and significantly lower with
non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission
to liver recipients from isolated HBV core antibody
positive (anti-HBcþ) donors. Organs from anti-HBcþ
donors should be considered for all adult transplant
candidates after an individualized assessment of the
risks and benefits and appropriate patient consent.
Indefinite antiviral prophylaxis is recommended in liver
recipients with no immunity or vaccine immunity but
not in liver recipients with natural immunity. Antiviral
prophylaxis may be considered for up to 1 year in
susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no
longer the treatment of choice in patients with chronic
HBV, lamivudine remains the most cost-effective
choice for prophylaxis in this setting. Hepatitis B
immunoglobulin is not recommended.
Abbreviations: anti-HBc, HBV core antibody; antiHBs, hepatitis B surface antibody; DNH, de novo
HBV; HBeAg, hepatitis B e antigen; HBIG, hepatitis B
immunoglobulin; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; hgbNA, nucleot(s)ide
analogues with high genetic barrier to resistance;
KT, kidney transplantation; LT, liver transplant; NAT,
nucleic acid testing; OPOs, organ procurement
organizations; OPTN, Organ Procurement Transplant Network; U.S., United States
Received 12 September 2014, revised 08 December
2014 and accepted for publication 24 December 2014
Introduction
Despite concerted efforts to safely expand the donor organ
pool, there is a widening gap between organ availability and
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Transplantation From Hepatitis B Virus–Positive Donors
demand (1). In the United States (U.S.), organ donation has
plateaued at approximately 8000 deceased donors per year
since 2004 and 5800 living donors per year since 2006.
Overall, the number of organs transplanted in the U.S. has
reached a plateau of approximately 31 000 per year. In
contrast, the recipient waiting list has steadily increased
to over 122 000 candidates (2). Consequently, novel
approaches to safely expand the organ supply are
desperately needed. Donation after circulatory death has
emerged to be a significant portion of the U.S. donor
population (1–3). Likewise, living donation from unrelated
‘‘altruistic’’ donors and paired kidney exchanges has also
increased (1,4,5).
Use of organs from donors with infections that can be
prevented or easily managed in the recipient is another
potential source to expand the donor pool. In this regard,
individuals who test positive for hepatitis B virus (HBV)
should be considered for deceased or living donation. The
risk of transmission can be significantly reduced with
prophylaxis. In the event of transmission, HBV can be
readily managed utilizing similar antiviral therapeutic
approaches as in patients with chronic HBV who undergo
transplantation. This document reviews the literature
regarding liver, kidney, and thoracic transplantation from
donors with HBV infection and outlines recommendations
for the use of such organs and subsequent recipient
management.
rates (2–8%) in Mediterranean countries and Japan; and
high rates (8–20%) in Southeast Asia and sub-Saharan
Africa (9,10). Similarly, the prevalence of anti-HBc positive
liver donors also varies geographically: 2–9% in the U.S.;
7–12% in Europe and Japan; and 53–57% in China and
Taiwan (11).
HBV virology and diagnostics
HBV is a double-stranded enveloped DNA virus of the family
Hepadnaviridae. Although HBV primarily replicates within
hepatocytes, extrahepatic replication may also occur (7,8).
Furthermore, HBV DNA may be detected in the bloodstream with viremia surpassing >109 IU/mL. Consequently,
the risk of transmission is highest with liver allografts but
also may occur with other transplanted organs. The natural
course of HBV infection has been fully reviewed elsewhere (12,13). Testing for HBV serologic markers is
essential in the diagnosis of HBV infection. The interpretation of HBV serologic markers is summarized in Table 1. The
presence of HBV DNA, hepatitis B surface antigen (HBsAg),
and hepatitis B e antigen (HBeAg) are markers of active
infection and IgM hepatitis B core antibody (IgM anti-HBc) is
a marker of acute or reactivated infection. The presence of
hepatitis B surface antibody (anti-HBs) is a marker of
immunity. Finally, the presence of hepatitis B core antibody
(anti-HBc) in the absence of HBsAg may represent a falsepositive result, past exposure to HBV with resolved or
resolving infection, or rarely occult chronic HBV infection
with detectable HBV DNA.
Methods
To develop consensus recommendations regarding the use of organs from
HBV positive donors, the American Society of Transplantation assembled an
expert group with representatives from the following adult and pediatric
transplant disciplines: infectious diseases, hepatology, nephrology, pulmonary, cardiology, pharmacy, and organ procurement. Working groups were
formed to review the epidemiology of HBV in transplantation and the impact
of HBV positive donors in kidney, liver, and thoracic transplantation. Each
working group brought forth recommendations to the overall group. A
systematic literature review was performed using PubMed with the
following search terms: hepatitis B, transplant, donor, outcome, and
transmission. The GRADE system (6) was used to measure the strength
of recommendations as strong or weak and the quality of evidence as high,
moderate, or low. Consensus was reached via small and large group
teleconferences.
Background
HBV epidemiology
The use of donors who test positive for HBV is essential to
maximizing the potential deceased donor pool as approximately one-third of the global population has serological
evidence of past or current HBV infection including 350–
400 million people with chronic HBV infection (7,8). The
prevalence of chronic HBV infection in the general
population differs dramatically between regions with low
rates (2%) in Western Europe and the U.S.; intermediate
American Journal of Transplantation 2015; 15: 1162–1172
HBV immunization
The HBV vaccine provides a significant level of protection against HBV infection, particularly in those who
achieve protective antibody response (anti-HBs concentration of >10 IU/mL) before HBV exposure. In immunocompetent individuals, vaccination is thought to provide
lifelong immunity even if anti-HBs titers wane. However,
in immunocompromised individuals, maintenance of a
protective anti-HBs titer may be necessary for ongoing
protection (14). Whenever possible, the vaccine series
should be given prior to transplantation in non-immune
individuals since the vaccine is less effective after
transplantation (15–18). The higher dose (40 mg antigen
per dose) vaccine is recommended in the pretransplant
setting in hemodialysis patients and other immunocompromised hosts due to decreased response rates with
standard dosing. Children under the age of 18 years who
do not seroconvert with standard dosing can receive
vaccine with 20 mg antigen per dose as this dose has
been shown to be immunogenic in children and
adolescents with chronic kidney disease (19). The higher
dose vaccine is also recommended in transplant
recipients. Serologic testing of anti-HBs 1–2 months
after completion of the vaccine series should be
performed to confirm immunity or the need for repeating
vaccination (20–22).
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Huprikar et al
Table 1: Interpretation of serologic tests for HBV adapted
from (86)
HBsAg negative
anti-HBc negative
anti-HBs negative
No infection or immunity
HBsAg negative
Natural immunity
recipients demonstrated higher rates of HBV recurrence
with hepatitis B immunoglobulin (HBIG)/lamivudine (6.1%)
compared to HBIG/hgbNA (1%) (29). As a result of effective
antiviral therapy, use of HBIG passive immunization has
decreased in LT recipients with chronic HBV, and some
centers have stopped using HBIG altogether (30). Excellent
outcomes are also observed in kidney and heart transplant
recipients with chronic HBV who are managed with antiviral
therapy alone (31).
anti-HBc positive
anti-HBs positive
HBsAg negative
Vaccine immunity
anti-HBc negative
anti-HBs positive
HBsAg positive
Acute infection
anti-HBc positive
IgM anti-HBc positive
anti-HBs negative
HBsAg positive
Chronic infection
anti-HBc positive
IgM anti-HBc negative
anti-HBs negative
HBsAg negative
Four possible interpretations:
anti-HBc positive
1. Resolved infection and immune
(most common)
anti-HBs negative
2. No infection or immunity (falsepositive anti-HBc)
3. Occult chronic infection
4. Resolving acute infection
Chronic HBV and transplantation
The primary goal of treatment in patients with chronic HBV
is virologic suppression. Posttransplant patient and graft
survival have improved dramatically with effective antiviral
therapy (23). Currently approved agents are summarized in
Table 2 (12). Historically, lamivudine was the primary
antiviral agent used for the treatment of chronic HBV both
before and after transplantation. More recently, highly
potent oral nucleos(t)ide analogs with a high genetic barrier
to resistance (hgbNA) such as entecavir and tenofovir have
emerged as the preferred agents. Entecavir and tenofovir
are both safe and effective as once daily oral therapy and are
now considered superior to lamivudine because of very low
resistance rates (<1%) in treatment na€ıve patients (24–28).
Furthermore, a systematic review of liver transplant (LT)
1164
Organ procurement organization practices: Donor
HBV testing and organ use
In the U.S., the current policy of the Organ Procurement
Transplant Network (OPTN) requires that all organ procurement organizations (OPOs) perform deceased donor
testing for HBsAg and anti-HBc (32). However, some
OPOs perform additional donor HBV testing that is not
mandated by OPTN to guide decisions about organ
donation. Although specific data on the frequency in which
donor organs are declined due to donor HBV testing results
are lacking, decisions to utilize anti-HBcþ organs are often
guided by additional tests with some OPOs routinely or
reflexively performing IgM anti-HBc, anti-HBs, and/or HBV
nucleic acid testing (NAT). These results are made available
rapidly for transplant centers that utilize this information in
decision-making. If the donor is IgM anti-HBc or HBV NAT
positive, many OPOs and transplant centers currently do
not accept such organs for donation due to concern for
acute, reactivated, or occult chronic HBV infection in the
donor. When the donor is anti-HBc IgG positive, some
OPOs and transplant centers will accept such organs but
there is no consistent approach to recipient management. It
is debatable whether these additional tests are helpful in
further stratifying transmission risk from an anti-HBcþ
donor without features of clinical hepatitis. For example,
there are no data to suggest that the anti-HBs status of an
HBsAg– anti-HBcþ donor impacts the risk of HBV
transmission to recipients yet this information is anecdotally used to assess donor acceptability. OPOs and transplant
centers in the U.S. rarely use organs from HBsAgþ donors.
OPTN policy requires that potential living donors are tested
for HBsAg, anti-HBs, and anti-HBc (33). Potential living
donors who are anti-HBcþ or HBsAgþ should undergo
further testing with HBV DNA and evaluation for chronic
HBV infection prior to organ donation consideration.
Review of literature: Isolated anti-HBcþ donors
The risk of HBV transmission from anti-HBcþ HBsAg–
donors is observed mainly in liver transplant recipients.
Transmission is significantly lower in kidney transplant
recipients and essentially negligible in thoracic transplant
recipients. Data are limited by variability in reporting donor
and recipient transmission risk factors. There is also
significant variation in the definition of HBV transmission
ranging from the acquisition of anti-HBs and/or anti-HBc
alone to the acquisition of HBsAg or detection of HBV DNA.
American Journal of Transplantation 2015; 15: 1162–1172
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Transplantation From Hepatitis B Virus–Positive Donors
Table 2: Nucleos(t)ide analogues for the treatment of HBV
Nucleos(t)ide
analogues
Oral daily
dosing for
HBV*
Adverse effects
Gastrointestinal
Age 18:
Lamivudine
effects,
(Epivir HBV1)100 mg
headache,
Age 2–18:
3 mg/kg (max lactic acidosis
100 mg)
Monthly cost
in the U.S.
(average
wholesale
price) (87)
$483.33
(Lamivudine
HBV 100 mg
tablets)
$214.83
(Lamivudine
150 mg
tablets)
$166.30
Epivir1
10 mg/ml
(10 ml/day)
oral solution)
Age 16:
Gastrointestinal
Entecavir
$1397.33
effects,
(Baraclude1) Nucleoside(Baraclude1
treatmentheadache,
0.5 mg or
na€ıve
myalgia,
1 mg tablets
patients:
neuropathy,
or 0.05 mg/ml
0.5 mg
lactic acidosis
(10 ml/day)
Lamivudine
oral solution)
refractory:
1 mg
$1047.73
Tenofovir
Age 12:
Gastrointestinal
(Viread1
(Viread1)
300 mg
effects, rash,
300 mg tablets)
Age 2–11:
lactic acidosis,
8 mg/kg (max renal impairment $2142.37
(Viread1
300 mg)
(acute renal
40 mg/gm
failure, acute
(300 mg/day)
interstitial
oral powder)
nephritis,
Fanconi
syndrome),
decreased bone
mineral density
immune (anti-HBcþ anti-HBsþ) recipient. In this study,
the onset of DNH ranged from 2 to 39 months after
transplantation. In a more recently published review, the
rates of DNH without prophylaxis were 58% (81/140) in
HBV non-immune; 18% (6/34) in previously vaccinated;
14% (5/35) in isolated anti-HBcþ; and 4% (3/70) in naturally
immune recipients (35). It should be emphasized that the
absence of HBV DNA in donor serum does not preclude
transmission of HBV to liver recipients (36).
De novo HBV from anti-HBcþ donors with prevention
strategy: Several preventive strategies have been employed to prevent DNH infection in HBsAg– recipients. A
survey of LT programs conducted in 2007 revealed that
indefinite antiviral therapy was the most frequent treatment
strategy with lamivudine as the preferred antiviral agent and
significant variation in HBIG usage (37). Four studies have
reviewed the risk reduction associated with antiviral and/or
HBIG prophylaxis (11,34–36). In the most recently published review (35), prophylaxis (lamivudine and/or HBIG)
reduced rates of DNH from 58% to 11% in HBV nonimmune recipients; 18% to 2% in previously vaccinated
recipients; and 14% to 3% in isolated anti-HBcþ recipients
although the difference was not statistically significant in
this final group. Prophylaxis did not further reduce the risk of
DNH in naturally immune recipients (3% vs. 4%). However,
another review (11) demonstrated a lower risk of DNH in
anti-HBcþ recipients who received prophylaxis (3.4% vs.
15.2%). The lowest rate of DNH was observed in
vaccinated recipients who received prophylaxis (11,35,38).
The importance of adherence to antiviral prophylaxis was
noted in a study where DNH was observed in five patients
who were not adherent to lamivudine (39).
Liver transplantation
Although significant risk reduction of DNH is observed with
lamivudine, the benefit is marginal with HBIG monotherapy (35). Furthermore, the addition of HBIG does not confer
superior protection to lamivudine alone as Saab et al
demonstrated a DNH rate of 2.7% with lamivudine
prophylaxis compared to 3.6% with lamivudine plus
HBIG (34). This finding was also confirmed in a systematic
review (11) and in a single center study of 45 patients that
demonstrated complete protection against DNH with
lamivudine alone (40).
De novo HBV from anti-HBcþ donors without prevention strategy: There is a significant risk of de novo HBV
(DNH) in HBsAg– LT recipients of anti-HBcþ donor
livers (11,34–36). Methods for the detection of post-LT
DNH vary but typically rely on the new appearance of
HBsAg or HBV DNA. Yen et al identified 90 cases of DNH
among 194 liver recipients who did not receive HBIG or
antiviral prophylaxis (36). The majority of transmissions (82/
90) occurred in HBV non-immune recipients and DNH
occurred in 77% (82/107) of these recipients. However,
DNH also occurred in 18% (4/22) of previously vaccinated
recipients and in 13% (4/31) of isolated anti-HBcþ
recipients. DNH did not occur in any (0/34) naturally
Since entecavir and tenofovir have supplanted lamivudine
in the treatment of chronic HBV, many centers are now
using entecavir and tenofovir in recipients of anti-HBcþ
donors (41,42). Although anecdotes of lamivudine-resistant
HBV transmission are described with lamivudine prophylaxis (39), the use of lamivudine in recipients of anti-HBcþ
donors is still relevant. A retrospective study of 119 LT
patients without chronic HBV who received anti-HBcþ
livers showed minimal differences in DNH rates when
comparing lamivudine (5/62, 8%) with adefovir (5/33, 15%),
tenofovir (0/3), or entecavir (0/1) (42). Furthermore, a recent
study used a Markov model to demonstrate that lamivudine
*
Dose adjustment required for renal impairment.
American Journal of Transplantation 2015; 15: 1162–1172
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Huprikar et al
remains the most cost-effective option for preventing DNH
in the context of anti-HBcþ donors (43).
Kidney transplantation
The reported risk of DNH in HBV na€ıve kidney recipients
ranges from 0% to 27% (44). The risk of transmission is
influenced by recipient HBV immunity and possibly by
prophylaxis (45). In a recent review of nine studies with
1385 HBsAg– kidney recipients from anti-HBcþ donors (46),
new HBV serologic markers were observed in only 45
(3.2%) patients. Although this study did not explore the
influence of recipient anti-HBs status and use of prophylactic therapy, the rate of HBsAg acquisition was only 0.28%
(4/1385) with no evidence of symptomatic hepatitis. Patient
and graft outcomes were not worse among the patients
with HBsAg acquisition or evidence of anti-HBs or anti-HBc
seroconversion.
The largest single study reported the incidence of anti-HBc
conversion in kidney recipients from the United Network for
Organ Sharing (UNOS) database with posttransplant
surveillance intervals of 6, 12, 24, and 36 months. The
incidence of anti-HBc seroconversion with anti-HBcþ
donors was higher compared to anti-HBc– donors at
0.011 (95% CI 0.0070–0.0182) and 0.005 (95% CI
0.0047–0.0060) cases per year (p < 0.002), respectively (47). However, HBsAg acquisition was similar and
occurred at a rate of 0.001 (95% CI 0.003–0.005) and
0.003 (95% CI 0.0025–0.0035) from anti-HBcþ and antiHBc– donors, respectively.
HBV vaccination prior to transplant, with target anti-HBs
titers >10 IU/L, has been demonstrated to be protective for
renal recipients of anti-HBcþ donors (45,48,49). Rarely,
individuals have had asymptomatic anti-HBc seroconversion
following transplantation from anti-HBcþ donors. However,
it is not clear if this truly represents DNH. Clinical hepatitis
has not been noted in immunized individuals following
kidney transplantation (KT) from anti-HBcþ donors, possibly
due to partial protection from vaccination (50,51). Whether
higher target levels of antibody will convey greater protection, as shown in LT recipients (52), is unclear. However in
another series, the risk of anti-HBc seroconversion was
reported to be 4% when anti-HBs titers were >100 IU/L
compared to 10% when <100 IU/L(53). In another study (54)
anti-HBc or anti-HBs seroconversion rates were similar in
immunized and non-immunized recipients although the nonimmunized recipients were treated with HBIG.
Other information regarding the use of HBIG in kidney
recipients from anti-HBcþ donors is limited, and it is unknown
if there is any benefit for recipients who have pre-existing
antibody, especially if the donor is surface antigen and/or DNA
negative (49,54–56). Although non-immune recipients of antiHBcþ kidneys who do not receive antiviral prophylaxis may
benefit from HBIG (49,54) data demonstrating this benefit are
lacking. The use of antiviral prophylaxis is rarely reported. In a
1166
single center observational study of 46 kidney or pancreas
recipients of anti-HBcþ organs, there was no evidence of HBV
transmission after a median of 36 months of follow-up (57).
Immune recipients were not treated whereas the others were
treated with lamivudine for 1 year. There is likely no role for
HBIG in the setting of antiviral prophylaxis although this has
not been studied.
Thoracic transplantation
Five studies with 122 transplantations provide data on the risk
of transmission from anti-HBcþ heart donors (58–62). Early
studies reported on patients without prophylaxis and did not
reveal any HBV transmission in over 80 patients; some of
whom were likely vaccinated prior to transplant (58–60,62). A
later study included 33 donor/recipient pairs of which five
received 6 months of lamivudine prophylaxis posttransplant (61). One anti-HBs– recipient did not receive prophylaxis
and developed clinically significant DNH at 10 months
posttransplant. Two others (one received lamivudine prophylaxis) seroconverted anti-HBs but without evidence of clinical
hepatitis. Thus, the incidence of donor-transmitted clinically
significant DNH was 1/33 or 3% in this study.
Three studies that included 369 transplantations provide
data on the outcomes from anti-HBcþ lung donors (63–65).
An analysis of UNOS data compared the results of 13,233
recipients of organs from anti-HBc– donors with 333
recipients of anti-HBcþ organs for lung and heart-lung
transplantation (63). Although one-year mortality was
higher in the anti-HBcþ donor group in unadjusted analysis,
there was no significant difference in five-year mortality,
and anti-HBcþ donor status was not an independent risk
factor for one-year or five-year mortality in the multivariable
analysis. Regarding the one-year unadjusted mortality, the
authors postulated that decompensated patients with
urgent need for transplantation may have been more likely
to receive anti-HBcþ donor organs.
Two studies evaluated HBV transmission in the context of
either pretransplant vaccination or posttransplant lamivudine prophylaxis (64,65). The first study evaluated 29
recipients of anti-HBcþ donor lungs who completed the full
series of HBV vaccination. Although anti-HBs response was
not confirmed, no cases of HBV transmission were
reported and no differences in 1-year survival were
found compared with recipients of anti-HBc– donor
lungs (65). In the second study, none of the seven
recipients who took 12 months of lamivudine prophylaxis
after receiving an anti-HBcþ donor lung had evidence of
DNH although pretransplant HBV vaccination and serostatus of the recipients were not reported (64).
Review of literature: HBsAgþ donors
While organs from HBsAgþ donors are not routinely
transplanted in the U.S., there is evidence that patient and
graft outcomes are acceptable with appropriate recipient
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Transplantation From Hepatitis B Virus–Positive Donors
management. Previous guidelines have suggested consideration of organs from HBsAgþ donors in urgent non-renal
transplant candidates with HBIG/antiviral prophylaxis and
informed consent (31). Consideration should also be made in
endemic regions where potential donors are frequently
HBsAgþ.
Liver transplantation
Transplantation of HBsAgþ livers into three recipients with
chronic hepatitis B was described in one series (66). HBsAg
persisted after transplant despite treatment with HBIG and
antiviral therapy. Two of the recipients were co-infected
with hepatitis Delta virus (HDV) and HDV relapsed in the
setting of persistent HBsAg positivity and hepatitis. The
third recipient was treated with HBIG, lamivudine, and
adefovir and had stable graft function with negative HBV
DNA. In a single center study from Italy, HBsAgþ livers
were used in ten anti-HBcþ recipients (six with chronic
HBV). All ten were treated with antiviral prophylaxis, and
there was no evidence of DNH (67). A retrospective
analysis of UNOS data reviewed the outcomes in 92
recipients of HBsAgþ livers (68). Although HBsAgþ livers
were more likely to be imported or used in Model for EndStage Liver Disease (MELD) exception cases, there were
no differences in patient or graft survival when compared to
recipients of HBsAg– livers. In a single center study from
China (69), 23 recipients of HBsAgþ livers were followedup for 10–38 months. The patient and graft survival rates
were 78.3% (18/23) and 73.9% (17/23), respectively.
Although the recurrence rate of HBV infection was 100%
(23/23) and all patients remained HBsAgþ, no liver
dysfunction, graft loss, or death was found to be related
to the recurrence of HBV infection. Use of HBsAgþ donor
livers should only be considered when significant donor
liver disease has been ruled out by histological examination.
Kidney transplantation
The successful use of deceased and living donor HBsAgþ
kidneys has been described in 104 HBV immune (antiHBsþ) recipients (70). Prevention strategies included a
heterogeneous mix of vaccine, HBIG, and antiviral regimens although vaccine alone was used in 27 patients (70).
Jiang et al described 65 anti-HBsþ kidney recipients who
received HBsAgþ kidneys. HBIG was administered on the
day of surgery and repeated at 1 month. For seven
recipients of HBV DNAþ grafts, HBIG was given weekly
for 3 months and lamivudine was given for 6 months. After
a mean follow-up of 30 months, only one recipient acquired
HBsAg but without liver injury or detectable HBV DNA (55).
Tuncer et al described no DNH in 35 HBV immune (anti-HBs
>10 IU/L) patients who underwent KT from HBsAgþ, HBV
DNA negative living donors (71). Of considerable interest,
HBIG and antiviral prophylaxis was not utilized. In another
study, four naturally immune recipients were also treated
with 1 year of lamivudine with no evidence of HBV
transmission (57). In a recent study, the patient and graft
survival after a median of 58.2 months was not different in
American Journal of Transplantation 2015; 15: 1162–1172
HBsAg– recipients with anti-HBs titers >100 IU/L regardless of whether their graft was acquired from a HBsAgþ or
HBsAg– donor (72). None of the 43 recipients of an
HBsAgþ graft acquired HBV including 20 patients who
received no prophylaxis. The successful use of HBsAgþ
kidneys has also been demonstrated in HBsAgþ recipients (73). Of note, there is a report of fatal fulminant HBV
16 months after KT in a previously immunized (anti-HBsþ)
recipient from an HBsAgþ donor. Although HBIG and a
supplemental dose of HBV vaccine were administered,
antiviral prophylaxis was not given (74).
Thoracic transplantation
Limited data exist for the use of HBsAgþ donors in heart
transplantation. Most available data are published by one
group in Taiwan with the apparent inclusion of the same
subjects in more than one publication (62,75,76). Of at least
36 reported recipients of HBsAgþ donor hearts, HBsAg
acquisition was observed in two recipients. HBV transmission occurred in one of three anti-HBs– recipients although
the HBIG protocol was not completed in this patient. One of
the seven recipients who were anti-HBcþ prior to
transplant and received an HBsAgþ organ developed acute
HBV, but it is unclear if this was reactivation of recipient or
donor HBV. In contrast, HBV transmission was not
observed in the 23 anti-HBsþ recipients. In a post-hoc
analysis of a limited-access dataset of the United Network
for Organ Sharing database from 2000 to 2010, anti-HBcþ
donor status did not significantly affect overall survival of
thoracic transplant recipients (77). These limited data
suggest that effective pretransplant vaccination and possibly posttransplant HBIG prophylaxis can prevent HBV
transmission from HBsAgþ donor hearts. No data exist
for the use of HBsAgþ donors in lung transplantation.
Review of literature: Monitoring
No studies have been performed to assess the costeffectiveness or optimal frequency and type of monitoring
for the development of DNH after transplantation. Recognition of DNH may be challenging since the onset of infection is
not predictable and may be delayed for up to 5 years (78). For
recipients of anti-HBcþ livers, most of the studies have
described initial monitoring every 1–3 months for 1 year and
every 3–6 months after 1 year. For non-liver recipients,
optimal monitoring intervals have not been established.
Review of literature: Pediatrics
There is very limited evidence regarding the use of HBVþ
donor organs in children. Seki et al reported a case of a
7-year-old boy with posterior urethral valves who received
a KT from his mother who was HBsAgþ (79). The child
completed HBV vaccination prior to transplant, and was
anti-HBsþ 1 year later after which he was transplanted.
During transplant, he received HBIG. Two years after
transplant, he had no allograft rejection, kidney and liver
function remained normal, and he continued to be HBsAg–.
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Huprikar et al
Wei et al reported on 21 patients from Taiwan (age range of
11–50 years) who underwent KT from 12 HBsAgþ
deceased donors (80). Four (19%) of the 21 recipients
were also HBsAgþ prior to transplant. There was no
significant difference in mortality or graft failure between
the recipient group that was HBsAgþ before transplant and
the patients who were HBsAg– before transplant. However, two HBsAg– patients became HBsAgþ after transplant,
and both died. Although the youngest recipient in the study
was 11 years, the total number of children (<18 years)
included and outcomes were not specified.
Recommendations
General
1.
All transplant candidates should be tested for HBV
(HBsAg, anti-HBs, and anti-HBc) to optimize risk
assessment and guide management (strong recommendation; moderate quality of evidence).
2.
Before transplantation, HBV vaccination is recommended for all non-immune (anti-HBs–) transplant
candidates (strong; moderate).
There is currently insufficient evidence to support or refute
the use of anti-HBc þ positive or HBsAgþ organs in
pediatric KT recipients. In contrast to other organ transplants, KT is rarely lifesaving in the acute setting since
dialysis is typically an option for children with end stage
kidney disease which allows the potential recipient to be
selective towards high-risk donors. However, as more
children with end stage kidney disease are becoming highly
sensitized, the potential relative benefit of transplanting a
kidney from an anti-HBcþ donor into a highly sensitized
HBV immune child may have to be increasingly considered
on an individualized case basis.
3.
After transplantation, HBV vaccination is recommended for all non-immune transplant recipients
(strong; low).
4.
Recipients with chronic HBV infection should be
managed according to existing guidelines irrespective
of the donor HBV status (strong; moderate).
5.
Organs from HBsAg– anti-HBcþ donors regardless of
donor anti-HBs status should be considered for all adult
transplant candidates after an individualized assessment of the risks and benefits and appropriate patient
consent (strong; moderate).
Compared to pediatric KT, a relatively larger experience of
outcomes after pediatric LT with anti-HBcþ organs exists.
The majority of the reported data comes from Asia with a
total of 100 patients and an additional three patients reported
from Poland (38,52,81–85). Except for 19 cases from China,
all patients received routine vaccination in infancy and after
transplant. However, there was considerable variability in
the targeted anti-HBs titer goals, which ranged from 20 IU/L
to 1000 IU/L. Twenty-three of 103 (22.3%) pediatric
recipients of anti-HBcþ donors developed DNH after being
followed for 4–120 months posttransplant. Use of HBIG
either peri-transplant or as part of posttransplant prophylaxis
was variable across centers. Of note, 8 of 36 patients from a
single center in Taiwan developed DNH prior to the
implementation of peri-transplant HBIG, posttransplant
lamivudine and vaccination (52). In another study, 11 of 19
patients who received living donor transplants from antiHBcþ donors developed DNH. Eight of the 11 had no
evidence of anti-HBs prior to transplant (81). Overall,
vaccination appeared to be the most consistently employed
strategy in pediatric LT recipients who received an antiHBcþ organ and was associated with a DNH rate of 15.7%.
Optimal methods for preventing DNH in the pediatric
population cannot be delineated based on this data. Although
advanced planning is required and the complexity of both
peri-operative and post-operative care increases, it appears
that appropriate recipient management may increase
feasibility of using anti-HBcþ donor livers in children. In
low HBV prevalence areas such as the U.S., the option of
using an anti-HBcþ liver should be confined to emergent
situations or other unique situations after careful consideration of risks and benefits. The optimal method of preventing
DNH is unclear and will evolve based on further experience.
6.
Organs from HBsAg– anti-HBcþ donors should only be
considered in emergent settings for pediatric transplant candidates in low prevalence areas after an
individualized assessment of the risks and benefits and
appropriate patient consent (strong; low).
7.
DNH should be considered with clinical hepatitis or
detection of HBV DNA, HBsAg, or anti-HBc (strong;
moderate).
8.
Consultation with a hepatologist or infectious diseases
specialist with transplant experience is recommended
when considering accepting an organ from an antiHBcþ or HBsAgþ donor or when there is concern for
DNH (strong; low).
1168
Liver transplant recipients from anti-HBcþ HBsAg–
donors (Figure 1)
9.
Indefinite antiviral prophylaxis is recommended in HBV
susceptible (anti-HBc– anti-HBs–) liver transplant
recipients (strong; moderate).
10. Antiviral prophylaxis is recommended in recipients
with vaccine immunity (anti-HBc– anti-HBs þ) (strong;
moderate).
11. Antiviral prophylaxis is not recommended in recipients
with natural immunity (anti-HBcþ anti-HBs þ) (weak;
moderate).
12. Lamivudine is recommended as the most costeffective choice for prophylaxis (strong; moderate).
13. Entecavir or tenofovir may also be considered for
prophylaxis due to their higher genetic barrier to
resistance (strong; low).
American Journal of Transplantation 2015; 15: 1162–1172
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Transplantation From Hepatitis B Virus–Positive Donors
Figure 1: Algorithm for use of liver grafts from anti-HBcþ donors in recipients without chronic HBV.
14. Discontinuation of prophylaxis may be considered
after 1 year in recipients with confirmed persistence of
immunity (anti-HBs 10 IU/mL) (strong; low).
15. HBIG is not recommended (strong; moderate).
16. HBV DNA with or without HBsAg should be monitored
every 3 months for 1 year and then every 3–6 months
indefinitely in all recipients regardless of current or
prior prophylaxis strategy (strong; low).
Non-liver transplant recipients from anti-HBcþ HBsAg–
donors (Figure 2)
17. Antiviral prophylaxis for up to 1 year may be considered
in HBV susceptible (anti-HBc– anti-HBs–) recipients
(weak; low).
20. HBIG is not recommended (strong; moderate).
21. HBV DNA with or without HBsAg should be monitored
every 3 months for 1 year (weak; low).
Recipients of any organ from HBsAgþ donors
22. Organs from HBsAgþ donors may be carefully
considered in all adult transplant candidates after an
individualized assessment of the risk and benefits and
appropriate patient consent (weak; low).
23. HBsAgþ livers should only be considered when
significant donor liver disease has been ruled out by
histology (strong; low).
24. Indefinite prophylaxis with entecavir or tenofovir is
recommended for all recipients (strong; low).
18. Lamivudine is the recommended choice for prophylaxis (strong; moderate).
25. HBIG should be considered in all recipients when the
anti-HBs titer is <100 IU/L (strong; low).
19. Antiviral prophylaxis is not recommended for recipients with natural (anti-HBcþ anti-HBsþ) or vaccine
(anti-HBc– anti-HBsþ) immunity (strong; moderate).
26. HBV DNA with or without HBsAg should be monitored
every 3 months for 1 year and then every 3–6 months
indefinitely (strong; low).
Figure 2: Algorithm for use of non-liver grafts from anti-HBcþ donors in recipients without chronic HBV.
American Journal of Transplantation 2015; 15: 1162–1172
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Practice Gaps
Although the recommendations in this guidance document
are based on careful analysis and review of the best
available evidence, it should be emphasized that some of
the evidence has been assessed as low quality. Studies are
needed in the following areas to improve the quality of
evidence and strengthen the validity of the
recommendations:
1. Donor and recipient risk factors for DNH.
2. The impact of further HBV testing of HBsAgþ or antiHBcþ donors on recipient management and outcomes.
3. Optimal choice and duration of prevention strategies for
non-immune recipients for each organ type.
4. The need for prevention strategies in immune recipients
for each organ type.
5. Optimal testing, frequency, and duration of monitoring
for each organ type.
6. The safety of using HBsAgþ organs.
Acknowledgments
The authors thank Leah Casner for her assistance in formatting the
manuscript. The authors thank Jacqueline O’Leary for her input in
developing the recommendations. The views expressed in this article are
those of the authors and do not necessarily reflect the official policy or
position of the Department of the Army, the Department of Defense, nor
the U.S. Government.
Disclosure
The authors of this manuscript have no conflicts of interest
to disclose as described by the American Journal of
Transplantation.
References
1. Israni AK, Zaun DA, Rosendale JD, Snyder JJ, Kasiske BL. AOPTN/
SRTR 2011 Annual Data Report: Deceased organ donation. Am J
Transplant 2013; 13: 179–198.
2. OPTN Data 2014; Available from: http://www.unos.org/.
3. Reich DJ, Mulligan DC, Abt PL, et al. ASTS recommended practice
guidelines for controlled donation after cardiac death organ
procurement and transplantation. Am J Transplant 2009; 9:
2004–2011.
4. Roodnat JI, Kal-van Gestel JA, Zuidema W, et al. Successful
expansion of the living donor pool by alternative living donation
programs. Am J Transplant 2009; 9: 2150–2156.
5. Roodnat JI, Zuidema W, van de Wetering J, et al. Altruistic donor
triggered domino-paired kidney donation for unsuccessful couples
from the kidney-exchange program. Am J Transplant 2010; 10:
821–827.
1170
6. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging
consensus on rating quality of evidence and strength of
recommendations. BMJ 2008; 336: 924–926.
7. European Association for the Study of the Liver. EASL clinical
practice guidelines: Management of chronic hepatitis B virus
infection. J Hepatol 2012; 57: 167–185.
8. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009; 373:
582–592.
9. Kao JH, Chen DS. Global control of hepatitis B virus infection.
Lancet Infect Dis 2002; 2: 395–403.
10. Kao JH. Role of viral factors in the natural course and therapy of
chronic hepatitis B. Hepatol Int 2007; 1: 415–430.
11. Cholongitas E, Papatheodoridis GV, Burroughs AK. Liver grafts
from anti-hepatitis B core positive donors: A systematic review. J
Hepatol 2010; 52: 272–279.
12. Lok AS, McMahon BJ. Chronic hepatitis B: Update 2009.
Hepatology 2009; 50: 661–662.
13. Yapali S, Talaat N, Lok AS. Management of hepatitis B: Our
practice and how it relates to the guidelines. Clin Gastroenterol
Hepatol 2014; 12: 16–26.
14. Stevens CE, Alter HJ, Taylor PE, Zang EA, Harley EJ, Szmuness W.
Hepatitis B vaccine in patients receiving hemodialysis. Immunogenicity and efficacy. New Eng J Med 1984; 311: 496–501.
15. Danzinger-Isakov L, Kumar D. Practice ASTIDCo. Guidelines for
vaccination of solid organ transplant candidates and recipients. Am
J Transplant 2009; 9: S258–S262.
16. Lefebure AF, Verpooten GA, Couttenye MM, De Broe ME.
Immunogenicity of a recombinant DNA hepatitis B vaccine in renal
transplant patients. Vaccine 1993; 11: 397–399.
17. Feuerhake A, Muller R, Lauchart W, Pichlmayr R, Schmidt FW.
HBV-vaccination in recipients of kidney allografts. Vaccine 1984; 2:
255–256.
18. Carey W, Pimentel R, Westveer MK, Vogt D, Broughan T. Failure of
hepatitis B immunization in liver transplant recipients: Results of a
prospective trial. Am J Gastroenterol 1990; 85: 1590–1592.
19. Watkins SL, Alexander SR, Brewer ED, et al. Response to
recombinant hepatitis B vaccine in children and adolescents with
chronic renal failure. Am J Kidney Dis 2002; 40: 365–372.
20. Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive
immunization strategy to eliminate transmission of hepatitis B
virus infection in the AT States: Recommendations of the
Advisory Committee on Immunization Practices (ACIP) Part II:
Immunization of adults. MMWR Recomm Rep 2006; 55: 1–33
quiz C E1–E4.
21. Dominguez M, Barcena R, Garcia M, Lopez-Sanroman A, Nuno J.
Vaccination against hepatitis B virus in cirrhotic patients on liver
transplant waiting list. Liver Transplant 2000; 6: 440–442.
22. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice
guideline for vaccination of the immunocompromised host. Clin
Infect Dis 2014; 58: e44–100.
23. Papatheodoridis GV, Sevastianos V, Burroughs AK. Prevention of
and treatment for hepatitis B virus infection after liver transplantation in the nucleoside AT era. Am J Transplant 2003; 3: 250–258.
24. Sherman M, Yurdaydin C, Sollano J, et al. Entecavir for treatment
of lamivudine-refractory, HBeAg-positive chronic hepatitis B.
Gastroenterology 2006; 130: 2039–2049.
25. Sherman M, Yurdaydin C, Simsek H, et al. Entecavir therapy for
lamivudine-refractory chronic hepatitis B: Improved virologic,
biochemical, and serology outcomes through 96 weeks. Hepatology 2008; 48: 99–108.
26. Gish RG, Lok AS, Chang TT, et al. Entecavir therapy for up to
96 weeks in patients with HBeAg-positive chronic hepatitis B.
Gastroenterology 2007; 133: 1437–1444.
American Journal of Transplantation 2015; 15: 1162–1172
guide.medlive.cn
Transplantation From Hepatitis B Virus–Positive Donors
27. Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to
5 years in patients with hepatitis B e antigen-positive chronic
hepatitis B. Hepatology 2010; 51: 422–430.
28. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during
treatment with tenofovir disoproxil fumarate for chronic hepatitis
B: A 5-year open-label follow-up study. Lancet 2013; 381: 468–475.
29. Cholongitas E, Papatheodoridis GV. High genetic barrier
nucleos(t)ide analogue(s) for prophylaxis from hepatitis B
virus recurrence after liver transplantation: A systematic
review. Am J Transplant 2013; 13: 353–362.
30. Lucey MR, Terrault N, Ojo L, et al. Long-term management of the
successful adult liver transplant: 2012 practice guideline by the
American Association for the Study of Liver Diseases and the
American Society of Transplantation. Liver Transplant 2013; 19: 3–26.
31. Levitsky J, Doucette K. Practice ASTIDCo. Viral hepatitis in solid
organ transplantation. Am J Transplant 2013; 13: 147–168.
32. Organ Procurement and Transplantation Network (OPTN) Policies.
2014. Available from: http://optn.transplant.hrsa.gov/ContentDocuments/OPTN_Policies.pdf#nameddest¼
Policy_2_Deceased_Donor_Organ_P.
33. Organ Procurement and Transplantation Network (OPTN) Policy:
Living Donation. 2013. Available from: http://optn.transplant.hrsa.
gov/PoliciesandBylaws2/policies/pdfs/policy_172.pdf.
34. Saab S, Waterman B, Chi AC, Tong MJ. Comparison of different
immunoprophylaxis regimens after liver transplantation with
hepatitis B core AT donors: A systematic review. Liver Transplant
2010; 16: 300–307.
35. Skagen CL, Jou JH, Said A. Risk of de novo hepatitis in liver
recipients from hepatitis-B core antibody-positive grafts - a
systematic analysis. ClinTransplant 2011; 25: E243–E249.
36. Yen RD, Bonatti H, Mendez J, Aranda-Michel J, Satyanarayana R,
Dickson RC. Case report of lamivudine-resistant hepatitis B virus
infection post liver transplantation from a AT B core antibody
donor. Am J Transplant 2006; 6: 1077–1083.
37. Perrillo R. Hepatitis B virus prevention strategies for antibody to
hepatitis B core antigen-positive liver donation: A survey of North
American, European, and Asian-Pacific transplant programs. Liver
Transplant 2009; 15: 223–232.
38. Lin CC, Chen CL, Concejero A, et al. Active immunization to
prevent de novo hepatitis B virus infection in pediatric live donor
liver recipients. Am J Transplant 2007; 7: 195–200.
39. Bohorquez HE, Cohen AJ, Girgrah N, et al. Liver transplantation in
hepatitis B core-negative recipients using livers from hepatitis B
core-positive donors: A 13-year experience. Liver Transplant 2013;
19: 611–618.
40. Vizzini G, Gruttadauria S, Volpes R, et al. Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients
with HBcAb-positive liver grafts. Clin Transplant 2011; 25:
E77–E81.
41. MacConmara MP, Vachharajani N, Wellen JR, et al. Utilization of
hepatitis B core antibody-positive donor liver grafts. HPB 2012; 14:
42–48.
42. Chang MS, Olsen SK, Pichardo EM, et al. Prevention of de novo
hepatitis B in recipients of core antibody-positive livers with
lamivudine and other nucleos(t) ides: A 12-year experience.
Transplantation 2013; 95: 960–965.
43. Wright AJ, Fishman JA, Chung RT. Lamivudine compared with
newer antivirals for prophylaxis of hepatitis B core antibody
positive livers: A cost-effectiveness analysis. Am J Transplant
2014; 14: 629–634.
44. Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR.
Review of the use of hepatitis B core antibody-positive kidney
donors. Transplant Rev 2010; 24: 167–171.
American Journal of Transplantation 2015; 15: 1162–1172
45. Pilmore HL, Gane EJ. Hepatitis B-positive donors in renal
transplantation: Increasing the deceased donor pool. Transplantation 2012; 94: 205–210.
46. Mahboobi N, Tabatabaei SV, Blum HE, Alavian SM. Renal grafts
from anti-hepatitis B core-positive donors: A quantitative review of
the literature. Transplant Infect Dis 2012; 14: 445–451.
47. Fong TL, Bunnapradist S, Jordan SC, Cho YW. Impact of hepatitis B
core antibody status on outcomes of cadaveric renal transplantation: Analysis of United network of organ sharing database
between 1994 and 1999. Transplantation 2002; 73: 85–89.
48. Sumethkul V, Ingsathit A, Jirasiritham S. Ten-year follow-up of
kidney transplantation from hepatitis B surface antigen-positive
donors. Transplant Proc 2009; 41: 213–215.
49. Veroux M, Corona D, Ekser B, et al. Kidney transplantation from
hepatitis B virus core antibody-positive donors: Prophylaxis with
hepatitis B immunoglobulin. Transplant Proc 2011; 43: 967–970.
50. Madayag RM, Johnson LB, Bartlett ST, et al. Use of renal allografts
from donors positive for hepatitis B core antibody confers minimal
risk for subsequent development of clinical hepatitis B virus
disease. Transplantation 1997; 64: 1781–1786.
51. De Feo TM, Grossi P, Poli F, et al. Kidney transplantation from antiHBcþ donors: Results from a retrospective Italian study.
Transplantation 2006; 81: 76–80.
52. Su WJ, Ho MC, Ni YH, et al. High-titer antibody to hepatitis B surface
antigen before liver transplantation can prevent de novo hepatitis B
infection. J Pediatr Gastroenterol Nutr 2009; 48: 203–208.
53. Fytili P, Ciesek S, Manns MP, et al. Anti-HBc seroconversion after
transplantation of anti-HBc positive nonliver organs to anti-HBc
negative recipients. Transplantation 2006; 81: 808–809.
54. Veroux M, Puliatti C, Gagliano M, et al. Use of hepatitis B core antibodypositive donor kidneys in hepatitis B surface antibody-positive and
-negative recipients. Transplant Proc 2005; 37: 2574–2575.
55. Jiang H, Wu J, Zhang X, et al. Kidney transplantation from
hepatitis B surface antigen positive donors into hepatitis B
surface antibody positive recipients: A prospective nonrandomized controlled study from a single center. Am J Transplant 2009;
9: 1853–1858.
56. Chung RT, Feng S, Delmonico FL. Approach to the management
of allograft recipients following the detection of hepatitis B virus
in the prospective organ donor. Am J Transplant 2001; 1:
185–191.
57. Akalin E, Ames S, Sehgal V, Murphy B, Bromberg JS. Safety of
using hepatitis B virus core antibody or surface antigen-positive
donors in kidney or pancreas transplantation. Clin Transplant 2005;
19: 364–366.
58. De Feo TM, Poli F, Mozzi F, et al. Risk of transmission of hepatitis B
virus from anti-HBC positive cadaveric organ donors: A collaborative study. Transplant Proc 2005; 37: 1238–1239.
59. Wachs ME, Amend WJ, Ascher NL, et al. The risk of transmission
of hepatitis B from HBsAg(), HBcAb(þ), HBIgM() organ donors.
Transplantation 1995; 59: 230–234.
60. Blanes M, Gomez D, Cordoba J, et al. Is there any risk of
transmission of hepatitis B from heart donors hepatitis B core
antibody positive? Transplant Proc 2002; 34: 61–62.
61. Pinney SP, Cheema FH, Hammond K, Chen JM, Edwards NM,
Mancini D. Acceptable recipient outcomes with the use of hearts
from donors with hepatitis-B core antibodies. J Heart Lung
Transplant 2005; 24: 34–37.
62. Ko WJ, Chou NK, Hsu RB, et al. Hepatitis B virus infection in heart
transplant recipients in a hepatitis B endemic area. J Heart Lung
Transplant 2001; 20: 865–875.
63. Dhillon GS, Levitt J, Mallidi H, et al. Impact of hepatitis B core
antibody positive donors in lung and heart-lung transplantation: An
1171
guide.medlive.cn
Huprikar et al
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
analysis of the United Network For Organ Sharing Database.
Transplantation 2009; 88: 842–846.
Shitrit AB, Kramer MR, Bakal I, Morali G, Ben Ari Z, Shitrit D.
Lamivudine prophylaxis for hepatitis B virus infection after lung
transplantation. Ann Thoracic Surg 2006; 81: 1851–1852.
Hartwig MG, Patel V, Palmer SM, et al. Hepatitis B core antibody
positive donors as a safe and effective therapeutic option to
increase available organs for lung transplantation. Transplantation
2005; 80: 320–325.
Franchello A, Ghisetti V, Marzano A, Romagnoli R, Salizzoni M.
Transplantation of hepatitis B surface antigen-positive livers into
hepatitis B virus-positive recipients and the role of hepatitis delta
coinfection. Liver Transplant 2005; 11: 922–928.
Loggi E, Micco L, Ercolani G, et al. Liver transplantation from
hepatitis B surface antigen positive donors: A safe way to expand
the donor pool. J Hepatol 2012; 56: 579–585.
Saidi RF, Jabbour N, Shah SA, Li YF, Bozorgzadeh A. Liver
transplantation from hepatitis B surface antigen-positive donors.
Transplant Proc 2013; 45: 279–280.
Ju W, Chen M, Guo Z, et al. Allografts positive for hepatitis B
surface antigen in liver transplant for disease related to hepatitis B
virus. Exp Clin Transplant 2013; 11: 245–249.
Singh G, Hsia-Lin A, Skiest D, Germain M, O’Shea M, Braden G.
Successful kidney transplantation from a hepatitis B surface
antigen-positive donor to an antigen-negative recipient using a
novel vaccination regimen. Am J Kidney Dis 2013; 61: 608–611.
Tuncer M, Tekin S, Yucetin L, Sengul A, Demirbas A. Hepatitis B
surface antigen positivity is not a contraindication for living kidney
donation. Transplant Proc 2012; 44: 1628–1629.
Chancharoenthana W, Townamchai N, Pongpirul K, et al. The
Outcomes of kidney transplantation in Hepatitis B surface antigen
(HBsAg)-negative recipients receiving graft from HBsAg-positive
donors: A retrospective, propensity score-matched study. Am J
Transplant 2014; 14: 2814–2820.
Veroux P, Veroux M, Sparacino V, et al. Kidney transplantation
from donors with viral B and C hepatitis. Transplant Proc 2006; 38:
996–998.
Magiorkinis E, Paraskevis D, Pavlopoulou ID, et al. Renal
transplantation from hepatitis B surface antigen (HBsAg)-positive
donors to HBsAg-negative recipients: A case of posttransplant
fulminant hepatitis associated with an extensively mutated
hepatitis B virus strain and review of the current literature.
Transplant Infect Dis 2013; 15: 393–399.
Wang SS, Chou NK, Ko WJ, et al. Heart transplantation using
donors positive for hepatitis. Transplant Proc 2004; 36:
2371–2373.
1172
76. Chen YC, Chuang MK, Chou NK, et al. Twenty-four year singlecenter experience of hepatitis B virus infection in heart transplantation. Transplant Proc 2012; 44: 910–912.
77. Manickam P, Krishnamoorthi R, Kanaan Z, Gunasekaran PK,
Cappell MS. Prognostic implications of recipient or donor hepatitis
B seropositivity in thoracic transplantation: Analysis of 426
hepatitis B surface antigen-positive recipients. Transplant Infect
Dis 2014; 16: 597–604.
78. Avelino-Silva VI, D’Albuquerque LA, Bonazzi PR, et al. Liver
transplant from Anti-HBc-positive, HBsAg-negative donor into
HBsAg-negative recipient: Is it safe? A systematic review of the
literature. Clin Transplant 2010; 24: 735–746.
79. Seki T, Koyanagi T, Nonomura K, Yamashita T, Chikaraishi T,
Kanagawa K. Kidney transplantation in a child with posterior
urethral valve from a hepatitis B virus-carrier mother. Report of a
case with special reference to urinary tract reconstruction for
dysfunctionalized uropathies and seroimmunological preparation
against viral transmission. Urol Int 1998; 61: 237–239.
80. Wei HK, Loong CC, King KL, Wu CW, Lui WY. HBsAg(þ) donor as a
kidney transplantation deceased donor. Transplant Proc 2008; 40:
2097–2099.
81. Xi ZF, Xia Q, Zhang JJ, et al. De novo hepatitis B virus infection from
anti-HBc-positive donors in pediatric living donor liver transplantation. J Dig Dis 2013; 14: 439–445.
82. Jankowska I, Pawlowska J, Teisseyre M, et al. Prevention of de
novo hepatitis B virus infection by vaccination and high hepatitis B
surface antibodies level in children receiving hepatitis B virus core
antibody-positive living related donor liver: Case reports. Transplant Proc 2007; 39: 1511–1512.
83. Park JB, Kwon CH, Lee KW, et al. Hepatitis B virus vaccine switch
program for prevention of de novo hepatitis B virus infection in AT
patients. Transplant Int 2008; 21: 346–352.
84. Su WJ, Ho MC, Ni YH, et al. Clinical course of de novo hepatitis B
infection after pediatric liver transplantation. Liver Transplant 2010;
16: 215–221.
85. Kwon CH, Suh KS, Yi NJ, et al. Long-term protection against
hepatitis B in pediatric liver recipients can be achieved effectively
with vaccination after transplantation. Pediatr Transplant 2006; 10:
479–486.
86. A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States
Recommendations of the Advisory Committee on Immunization
Practices, Part 1 Immunization of Infants, Children, and Adolescents. MMWR Morb Mortal Wkly Rep 2005; p. 1–p.39.
87. Red Book Online1 [intranet database]. Version 5.1. Greenwood
Village, CO: Thomson Reuters (Healthcare) Inc.
American Journal of Transplantation 2015; 15: 1162–1172
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