Liver Transplantation: What's New?
- American Association for the Study of Liver Diseases
52nd Annual Meeting
[Medscape, 2001. � 2001 Medscape, Inc.]
Liver Transplantation: What's New?
Michael R. Lucey, MD
Two prominent themes were evident during the
proceedings of the 52nd Annual Meeting of the American
Association for the Study of Liver Diseases: (1)
living-donor liver transplantation (LDLT) between
adults, and (2) hepatitis C virus (HCV) infection in
liver transplant recipients.
This summary reviews a series of presentations that
advanced our understanding of these important topical
Adult-to-Adult Living-Donor Liver Transplantation
Brown and colleagues presented the results of a
survey on the practice of adult-to-adult LDLT in the
United States. The survey derived from a National
Institutes of Health-sponsored workshop on LDLT held
in December 2000, and concentrated on characteristics
of donors, donor evaluation, and donor outcome.
Eighty-six of the 112 United Network for Organ Sharing
(UNOS)-certified liver transplant programs responded.
The respondents accounted for more than 90% of all
transplants (cadaveric and live donors) being carried
out in the United States at that time.
The survey revealed that 43 (50%) centers had already
completed at least 1 adult-to-adult LDLT; 33 of the
remaining transplant programs indicated that they were
planning to start adult-to-adult LDLT. By November
2000, 449 adult-to-adult LDLTs had been completed, and
13 centers had done more than 10. Among donors, 75%
were family members, 11% were spouses, and 14% were
friends. The so-called "good Samaritan" donor was
rare. Typically, the evaluation included assessment by
a hepatologist, a medical social worker, and a
psychiatrist, and rarely involved an ethicist.
Regarding the use of invasive tests, 14% of programs
never did liver biopsies on potential donors, 60% used
biopsy selectively, and 26% of programs biopsied
everyone who met initial criteria. In contrast, the
majority (60%) of programs reported that they
performed angiograms in all likely donors, with 26%
using angiography selectively, and 14 never obtaining
angiograms at all. Fifty percent of programs did not
send donors to intensive care following surgery. The
complications recorded included 1 donor death,
reoperation in 4% of cases, and significant biliary
morbidity in 8%.
Although fewer data were recorded on recipient
characteristics and outcome, these investigators noted
that only 7 recipients did not meet criteria for a
cadaveric donor. The rates of vascular and biliary
complications in recipients of adult-to-adult LDLT
were appreciable: 109 (24%) and 41 (8%), respectively.
As discussed above, these findings represent important
data showing the emergence of a new technology. The
inclination to participate in this technologic
evolution is strong, and almost all transplant centers
have begun or plan to start adult-to-adult LDLT. Donor
evaluation practices are highly variable, as shown by
the lack of consensus on donor liver biopsy. The
survey also indicates that the morbidity for donor and
recipient is considerable. Up until this point, the
selection criteria for recipients have remained the
same as those used for reception of a cadaveric donor,
but whether this will continue to be the case is
Hepatitis C in Liver Transplantation
Forman and colleagues presented data from a
retrospective review of the UNOS database from 1992
through 1998. When the database was confined to
patients with known HCV antibody serology, informative
data were available on 11,036 primary graft
recipients. Potential interactions between HCV status,
donor and recipient characteristics, year of
transplantation, and outcome were assessed using Cox
Using this methodology, these investigators identified
an unexpected interaction (significant at the P < .001
level) between recipient sex, HCV infection, and
transplant outcome. Specifically, female recipients
who were anti-HCV-positive had a significantly worse
graft and patient survival than did female recipients
who were anti-HCV-negative -- graft survival was 56%
less and patient survival was 51% less in this former
group. This interaction was not accounted for by
either the sex of the allograft donor, or by a
preponderance of chronic cholestatic disorders such as
primary biliary cirrhosis, among the female recipients
who were HCV-negative.
The above interaction was a surprising and unexplained
result, especially because female sex is associated
with less aggressive HCV infection in the absence of
liver transplantation. The strength of the UNOS
database is its size, giving it the capacity to
identity previously unrecognized and unrecognizable
associations. Its weakness is that many potentially
interesting data are not included.
The present study "begs" for more information, such as
causes of death or graft loss among anti-HCV-positive
and -negative women. Elucidating the mechanism of the
negative interaction between female sex and HCV on
outcome after liver transplantation may provide new
insights into HCV infection.
Control of HCV Infection Before LDLT
At last year's meeting, 2 groups presented data on the
difficulty of eradicating HCV in anticipation of
cadaveric liver transplantation -- the so-called
"preemptive therapy." One problem posed by
preemptive therapy is that the interval for treatment
is dictated by the availability of a cadaveric donor
organ, and not by the virologic response to therapy.
Halprin and coworkers provided an interesting
variant on preemptive therapy by reporting on a single
center's experience administering anti-HCV
chemotherapy to candidates due to undergo LDLT. This
experience is important for at least 2 reasons. First,
as demonstrated, the LDLT allows the timing of
transplantation to be coordinated with the planned
antiviral therapy. Second, there are anecdotal data to
suggest that HCV infection may impair the regeneration
of the recipient right lobe. Thus, eradication of HCV
before the LDLT would obviate this problem.
Dynamics of HCV Immediately After Liver
Forns and coworkers described the kinetics of HCV
during the perioperative period. Twenty patients with
HCV-induced cirrhosis were studied before operation,
in the anhepatic phase, and at frequent intervals
The study authors found that the circulating hepatitis
C viral load declined during the anhepatic phase, and
demonstrated a continued decline after reperfusion.
The median decline during the anhepatic phase was 0.73
log10, and during reperfusion was 1.35 log10. The
median interval to nadir levels was 16 hours after the
start of the transplant. HCV became undetectable in
occasional samples in only 2 patients. After this
initial phase, there was a variable response of
circulating HCV. Quantitative levels of HCV rose to
pretransplant levels in 10 recipients, remained at a
low plateau in 4, and showed a further decline in 6.
Five of the latter 6 subjects manifesting a
second-phase decline were among the 8 recipients whose
immunosuppressive protocol did not include
Evolution of HCV quasispecies was analyzed in 9
recipients. Approximately equal numbers of patients
maintained their pretransplant profile of predominant
quasispecies as those in whom new or poorly
represented quasispecies became dominant in the
initial 120 hours.
These elegant data show that there is a dynamic flux
in circulating HCV levels during and immediately after
liver transplantation. These data suggest that the
nadir of circulating HCV occurs after reperfusion, and
may be influenced by choice of immunosuppressive
agent. Additionally, these findings suggest that
initiation of antiviral therapy in the first 24 hours
after transplantation may afford the best opportunity
to control the virus.
Early Treatment of HCV After Liver Transplantation
Also during last year's meeting, Didier Samuel
presented results from a randomized controlled trial
of combination therapy for HCV after liver
transplantation using interferon alfa-2b and
ribavirin. In this study, treatment was introduced
at least 6 months after transplantation.
Administration of combination antiviral therapy early
after liver transplantation is hindered by the renal
clearance of ribavirin, as many patients have some
degree of renal impairment after liver
During this year's meeting proceedings, Manzarbeitia
and colleagues presented preliminary results on the
use of interferon monotherapy with pegylated
interferon alfa-2a (40 kd; PEGASYS). Study entry was
restricted to patients who were positive for HCV RNA
in serum and had undergone primary liver
transplantation 3 weeks or less before randomization.
Data were presented on 33 subjects of a projected
recruitment of 50, who were randomized to receive
either 180 mcg pegylated interferon alfa-2a
subcutaneously per week or no antiviral treatment. To
date, 9 subjects in each treatment arm have completed
24 weeks of observation. The side-effect profile was
similar in both groups. At week 24, 44% of the treated
group had shown a 2 log10 decline in circulating
virus, and HCV RNA was undetectable in 22%. No subject
in the untreated group demonstrated a 2 log10 decline
in HCV RNA, and HCV was detectable in all untreated
Although these are preliminary data, they nevertheless
suggest that it may be possible to ameliorate the
circulating hepatitis C viral load by administration
of currently available antiviral agents. The results
of this and other clinical trials will be awaited
Findings reported by Forns and colleagues, as
described above, suggest that initiation of antiviral
therapy even earlier in the course of posttransplant
management may be useful. Given the complexity of
management of patients in the immediate postoperative
phase, the use of powerful antivirals after liver
transplantation -- especially early in the
postoperative period -- should be confined to
carefully conducted clinical trials.
1. Brown RS, Richardson M, Lai M, Everhart J, Russo
MW, Hoofnagle JH. Adult living donor liver
transplantation (LDLT) in the US: Results of a survey
from the NIH LDLT meeting. Hepatology. 2001;34:235A.
2. Forman LM, Lewis JD, Berlin JA, Lucey MR. The
interaction of recipient gender and hepatitis C
infection on patients and allograft survival after
orthotopic liver transplantation. Hepatology.
2001;34:244A. [Abstract 283]
3. Lucey MR. Liver transplantation and hepatitis C
infection. Medscape Conference Summaries from the
American Association for the Study of Liver Diseases
51st Annual Meeting. 2000. Medscape Gastroenterology.
Accessed November 21, 2001.
4. Halprin A, Trotter JF, Everson GT, et al.
Post-transplant eradication of hepatitis C by
pre-transplant treatment in living donor liver
transplant recipients. Hepatology. 2001;34:244A.
5. Forns X, Garcia M, Feliu A, et al. Hepatitis C
virus (HCV) kinetics and quasispecies evolution during
and immediately after liver transplantation.
Hepatology. 2001;34:362A. [Abstract 760]
6. Manzarbeitia C, Tepermann L, Chalasani N, et al.
Peginterferon alfa-2a (40KD) (Pegasys) as prophylaxis
against hepatitis C infection recurrence after liver
transplantation (LT): preliminary results of a
randomized, multicenter trial. Hepatology.
2001;34:406A. [Abstract 938]
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