Sunday Liver Transplantation
Topic Forum
G. Sayuk; T. Leet; M. Schnitzler; P. H.
Hayashi
Background:
Livers from deceased donors who donate at least one
other solid organ are not always utilized.
Hypothesis:
Increased donor age and obesity leads to liver
non-utilization in donors who successfully donate another organ.
Aim:
To determine the proportion of liver non-utilization
and associated risk factors in these deceased donors.
Methods:
We did a nested, case-control study using the UNOS
deceased donor database from 1987 to 2005. Only those donating at least one
solid organ were included. Donation was defined as engraftment into a
recipient. A case was a donor whose liver was not engrafted (LNE); controls
were donors whose liver was engrafted (LE). We did univariate
& multivariate analyses with donor age & obesity (BMI>30 kg/m2 or
95th weight percentile for pediatric donors) variables. Covariates included
non-heart beating donor (NHBD), inotropic support,
serum Na, death by cardiovascular or intracranial bleed event (CV/ICH), viral serologies, cancer, diabetes, hypertension, AST, bilirubin,
blood group, race & gender. Similar analyses were done for LNE subgroups:
liver not recovered (NR), recovered but not transplanted (RNT), recovered not
for transplant (RN4T), consent (for liver) not obtained (cNO)
or requested (cNR).
Results:
LNE occurred in 25% (23,373) of 91,362 deceased donors
who successfully donated another organ. This percent has fallen significantly
over time (87-90: 48%, 91-95: 29%, 96-00: 21%, 00-05: 16%, p<0.05). Of LNEs, 12,788 (55%) were NR, 5258 (23%) were RNT, 2414
(10%) were cNR (for liver), 2141 (9%) were cNO, & 772 (3%) were RN4T. On univariate
analysis, increased age & obesity were associated with LNE (p<0.05). On
multivariate analysis, increased age (e.g. OR: 2.5, 2.2-2.9, p<0.01 for
50-60 year olds) and obesity (OR 2.1, 1.9-2.3, p<0.01) remained significant.
Significant covariates included NHBD, high bilirubin, high AST, positive anti-HBc and antiHCV serologies. Adjusted population attributable risks were
highest for age over 49 (13.7%), obesity (8.8%) & elevated AST (16.7%).
Analysis across 5-year intervals and for LNE subgroups NR, RNT and RN4T yielded
similar results. cNO & cNR
were associated with NHBD, CV/ICH, bilirubin and AST, but not age or obesity.
Summary:
LNE in these otherwise suitable donors has declined
over time but remains significant. LNE was associated with age & obesity,
but LNE from lack of consent was not.
Conclusion:
The decline in LNE is likely due to the rise in demand
for livers and use of extended criteria. Further decreases in LNE may be
hindered by aging and increased obesity in the general population. Lack of
consent in LNE should be explored further.
S. N. Wong; R. Reddy; E. Keeffe;
S. Han; R. Perrillo; T. Tran; T. Pruett; A. S. Lok
Background:
Patients with HCC receive higher MELD scores and may
be transplanted earlier than those with cirrhosis, potentially decreasing
mortality on the waiting list. However, survival post-OLT may be reduced by
recurrence of HCC.
Aims:
To compare the rates of major outcomes (OLT, death,
disease [HBV and HCC] recurrence) between patients listed for HBV-cirrhosis (Gp 1) and patients listed for HBV-HCC (Gp
2), and to determine independent predictors of death and disease recurrence.
Methods:
All HBV patients with cirrhosis or HCC listed for
primary OLT in the US HBV-OLT study were included. Survival, disease
recurrence, and probability of OLT were estimated by Kaplan-Meier analysis.
Significant factors on univariate analysis were
entered into a Cox regression hazard model.
Results:
A total of 279 patients (Gp
1=183; Gp 2=96) were included. Gp
2 patients were older and more likely to be Asians, while Gp
1 patients had more severe liver impairment (MELD 15 vs. 9.5; p<0.001).
After a median follow-up of 29 months (12-46, 25-75% quartile) from listing, 17
patients in Gp 1 and 4 in Gp
2 died before OLT and 10 and 8 died after OLT. Overall survival was similar
despite a higher rate of OLT in Gp 2. MELD score at
listing (Hazard ratio [HR]: 1.1; 95% CI: 1.05-1.14) and being transplanted (HR:
4.5; 95% CI: 1.97-10.15) were independently associated with overall survival.
Ninety-four (51%) Gp 1 and 74 (77%) Gp 2 patients underwent OLT. Two Gp
2 and no Gp 1 patient were delisted
due to worsening disease. After a median of 18 months (9-33, 25-75% quartile)
post-OLT follow-up, 5 Gp 1 and 7 Gp
2 patients had HBV recurrence, and 6 Gp 2 patients
had HCC recurrence. Post-OLT survival, HBV recurrence, and disease
recurrence-free survival were similar in the 2 groups. HCC recurrence (HR: 5.7;
95% CI: 1.03-31.36) was the only independent predictor of post-OLT survival
(p=0.046).
Conclusions:
Despite more advanced liver disease and a lower rate
of OLT, overall survival of patients listed for HBV-cirrhosis was comparable to
those listed for HBV-HCC, possibly related to beneficial effects of antiviral
therapy. Higher MELD scores and absence of OLT predicted overall mortality,
while recurrence of HCC adversely affected post-OLT survival.
|
Probability (%) |
Gp 1 |
Gp 2 |
p-value |
|
Overall survival*
|
97, 86, 76 |
90, 85, 72 |
0.859 |
|
Death without
OLT* |
8, 12, 24 |
5, 5, 19 |
0.538 |
|
OLT* |
35, 53, 66 |
62, 83, 86 |
<0.001 |
|
Post-OLT
survival^ |
93, 90 |
91, 83 |
0.615 |
|
HBV recurrence^ |
2, 10 |
6, 11 |
0.421 |
|
Disease
recurrence^ |
2, 10 |
12, 19 |
0.062 |
|
Disease
recurrence-free survival^ |
93, 82 |
84, 78 |
0.328 |
204. Race Influences Access to Liver
Transplantation and Mortality on the Waiting-List
O. Khokhar; N. Ganeshan; L. Johnson; k. Shetty
African-Americans(AA)are believed to have reduced
access to various medical therapies; however, objective race-specific data
examining utilization of liver transplantation(LT)are sparse.
Aims :
To compare AA and Caucasians with regard to (a)
severity of liver disease at the time of listing for LT, as measured by the
Model for End-stage Liver Disease (MELD)score (b) mortality on the waiting
list.
Methods:
This was a retrospective analysis of the United
Network for Organ Sharing (UNOS) database on OLT registrants from 1997 to 2001,
aged between 18 and 70 years. Individuals lacking information on the variables
essential for calculation of the MELD score were excluded,as
were those designated as Hispanic. The Mann-Whitney t-test was used to compare
continuous variables, and the log-rank test to compare means. The Kaplan-Meier
method was used to compute transplant-free survivals on the waiting list.
Results :
A total of 4853 patients were included, over 85% of
these were Caucasian, and 60% were male. African-Americans accounted for 7.5%
of those listed. The overall rate of deceased donor transplantation was 28.5%,
and the mortality rate on the waiting list was 23.3%. The mean MELD score among
AA at the time of listing was 23 compared to 16 in Caucasians,
p=0.034.Mortality on the waiting list was significantly higher among AA than
among Caucasians ( 28. 5 % vs 21.7%, p = 0.02) The
rate of transplantation at 4 years from the time of listing was similar among
AA and Caucasians,as was the time to transplantation.This data is summarized in table 1.
Predictors of mortality on the waiting list were: age > 55 yrs, AA race,
MELD score.
Conclusions
(1) AA have a lower rate of registration on the LT
waiting list than would be expected from their representation in the US
population (2) AA are listed at a more advanced stage of disease severity, i.e higher MELD scores, than are Caucasians, presumably due
to delayed diagnosis and referral for transplantation. (3) The mortality of AA
on the waiting list is significantly higher than that of Caucasians (4) Once
listed for OLT, AA have similar rates of transplantation and waiting times. Our
data suggests a marked disparity in referral patterns and access to liver
transplantation among different racial groups, resulting in greater mortality
without benefit of transplantation in African-Americans.
|
|
All
Races |
African-Americans
|
Caucasians
|
p Value |
|
MELD score at
listing |
17 |
23 |
16 |
0.03* |
|
Mortality on
Waiting-List (%) |
23.3 |
28.5 |
21.7 |
0.02* |
|
Time to OLT (days) |
307 |
282 |
314 |
NS |
|
Rate of OLT within 4
years(%) |
28.5 |
28 |
29.4 |
NS |
205. Psychosocial Characteristics of Living
Liver Donors
A. Bhushan; S. Cotler; S. J. Cotler
Living liver donors (LD) volunteer to undergo a major
surgery for the sole purpose of helping a loved one. The behavioral and
psychological features of this fascinating group of people have not been well
characterized.
Aim
The aim of this study was to use a behavioral health
inventory to gain insight into the traits of LD.
Methods:
Living liver donor candidates were asked to complete
the Millon Behavioral Medicine Diagnostic (MBMD)
during the evaluation process. The MBMD is a validated, 164 item survey that
provides a detailed assessment of behavioral health domains. Computer scoring
generates normalized standard scores on a 100 point scale with 0-35
representing low values and >85 representing high values. Accompanying
interpretative reports address negative health habits, psychiatric status,
style of coping with illness, stress moderators, treatment prognostics, and
psychosocial attitudes. LD demographic data, post-operative pain medication
use, and number of post-operative outpatient visits were collected.
Results:
Subjects consisted of 11 LD who completed the MBMD.
Six (55%) were female, 9 (82%) were White, and 2 (18%) were African American.
Four (36%) subjects were married and 7 (64%) were single. Only 3 (27%) had more
than a high school education. All of the LD had successful recoveries. LD had
standard scores of 25±14 for anxiety and 22±16 for depression, well below the
normative mean. The personality profiles consisted of standard scores for
sociability (67±13) and confidence (74±13) that were well above the normative
mean. In qualitative analysis, LD presented themselves as calm, nonchalant,
self-assured, and as people who did not take illness very seriously. Moreover,
illness apprehension scores were low (29±18). Standard scores on the category
of problematic compliance were strikingly elevated (64±29), whereas reported
pain sensitivity was quite low (22±10). The sample was dichotomized between
deep spiritual and religious convictions (5/11) and those who reported a
complete absence of spirituality (5/11). There were no consistent relationships
among the MBMD domains and post-operative pain medication use, length of
hospital stay, or number of follow-up outpatient visits.
Conclusions:
The MBMD generated detailed psychosocial profiles of
living liver donors that could be useful in assessing liver donor candidates.
The LD in this sample were well-adjusted, sociable, confident, nonconforming,
and independent. The LD presented themselves as calm and nonchalant, suggesting
a certain amount of bravado and optimistic expectations about their
post-operative recovery.
206. Use Of Ethambutol And A Quinolone In Ppd
Positive Patients With Advanced Cirrhosis Before Or After Liver
Transplantation.
M. LaRocque; R. Lalonde; P. Ghali; N. Hilzenrat; J. Barkun; P. Metrakos; J. Tchervenkof; M. Deschenes
Background:
The 1st and 2nd line treatments for latent
tuberculosis (TB) are isoniazid for 9 months or rifampin for 4 months respectively. Both are hepatotoxic.
Patients under consideration for liver transplantation who have a positive PPD
need treatment for latent TB because the future use of antirejection
drugs constitutes a very high risk for TB reactivation. We have evaluated the
combination of ethambutol (EMB) 15mg/kg and a
quinolone in PPD positive patients with advanced liver disease or early after
liver transplantation when unable to tolerate the first or second line anti TB
treatment.
Objective:
To describe the outcome of 17 patients with advanced
liver disease or who are early after liver transplantation treated with EMB and
either 500mg of Ofloxacin (OFLOX) or 400mg of levofloxacin (LEVO) for a positive PPD.
Methods:
After obtaining ethics approval, a retrospective
analysis of data from the Royal-Victoria Hospital transplant clinic (Montreal,
Canada) database was performed. Hospital records were used to validate some
data.
Results:
We reviewed 17 patients with a positive PPD who were
treated with EMB and either OFLOX (15 pts) or LEVO (2 pts). There were 7 women
and 10 men, mean age 58 years old. Six patients underwent treatment shortly
before and 11 underwent treatment after liver transplantation. Patients
received anti-TB treatment for 9 to 12 months, except for one who died of acute
graft failure shortly after transplantation, and thus received therapy for only
7 months. Median follow-up was 32 months. No reactivation of TB was observed.
Routine ophthalmologic examination did not detect any cases of optic neuritis.
There was no decline in Child-Pugh score of any patient, except the one who
died of acute graft failure. Five patients died in the post transplant period,
none from TB or adverse effects attributed to EMB, OFLOX or LEVO. Two died of
recurrent hepatitis C, one of an angiosarcoma, one of
sepsis and one of graft failure.
Discussion:
The combination of EMB and a quinolone has been used
to treat latent TB with presumed drug-resistant bacteria. This is, to our
knowledge, the first report of its use in the context of advanced liver disease
and liver transplantation, when first and second line regimens were contraindicated.
The regimen was well tolerated and appears to have successfully prevented
reactivation of TB. We propose that the combination of EMB plus an anti-TB
quinolone seems to be an effective and safe alternative therapy in those
patients.