LIVER AND BILIARY DISEASE
Cost effectiveness of adjuvant therapy for hepatocellular
carcinoma during the waiting list for liver transplantation
J M Llovet, X Mas, J J Aponte, J Fuster, M Navasa, E Christensen, J Rodés, J Bruix
.............................................................................................................................
Gut 2002;50:123?128
Background: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened
by the increasing dropout rate while waiting for a donor.
Aims: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in
HCC patients.
Method: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was con-
sidered for: (1) adjuvant treatment?resection was limited to Child-Pugh?s A patients with single
tumours, and percutaneous treatment was considered for Child-Pugh?s A and B patients with single
tumours unsuitable for resection or with up to three nodules<3cm;and(2)standard management.
Length of waiting time ranged from six to 24 months.
Results: Surgical resection increased the transplantation rate (>10%) and provided gains in life
expectancy of 4.8?6.1 months with an acceptable cost ($40 000/ year of life gained) for waiting lists
>1 year whereas it was not cost effective ($74 000/life of year gained) for shorter waiting times or
high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2?6.7 months with
a marginal cost of approximately $20 000/year of life gained in all cases, remaining cost effective for
all waiting times.
Conclusions: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate
gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting
times, only percutaneous treatment confers a relevant survival advantage.
S
urgical resection and orthotopic liver transplantation
(OLT) are considered the first treatment options for
hepatocellular carcinoma (HCC) although the best treat-
ment strategy has not been established.
1
Resection achieves
good results in only a minority of patients but the long term
outcome is worsened by a high recurrence rate (three year
recurrence rate of 50%).
2?5
In contrast, liver transplantation
offers excellent results (70% survival with less than 20%
recurrence at five years) if the indication is restricted to
patients with single tumours <5 cm or three nodules <3
cm.
4 6?8
These values have prompted most hepatologists to
favour OLT as firstline treatment. However, the shortage of
donors and the increasing demand of organs have lengthened
waiting times to more than six or 12 months in Europe and
USA, respectively.
910
This delay can allow the tumour to grow
tostagesthatcontraindicateOLT.Wehaverecentlyshownthat
a waiting time longer than six months is associated with a
23% rate of dropout from the waiting list,
4
and values of up to
30?40% have been reported both in Europe and USA,
911
which
may reach 50% when expanded selection criteria are
applied.
12
This sharply worsens the outcome when assessing
OLT results on an intention to treat basis.
Several adjuvant antitumoral therapies have been adminis-
tered to patients on the waiting list for liver transplantation to
reducetumourgrowth.Themostcommontreatmentischemo-
embolisation, a palliative option that may achieve extensive
tumour necrosis.
13?18
However, there are no prospective studies
showing that it is effective in reducing the dropout rate or in
modifying the outcome of these patients. Surprisingly, the
usefulness of more radical options,such as resection or percu-
taneous ablation, that may provide the majority of patients
withcompletetumoralresponses,areseldomusedasadjuvant
treatments prior to OLT. Randomised controlled trials (RCTs)
assessing the benefits of any of these therapeutic approaches
are unlikely to be performed because they would be costly and
require a very large sample size. Therefore, we designed a
decision analysis to assess the impact of treating HCC patients
on the waiting list for OLT with the probability of being trans-
planted, overall survival, and cost effectiveness. Adjuvant
therapies included surgical resection and percutaneous
ablation as they provide a more extensive tumour load reduc-
tion than chemoembolisation. The model takes into account
the heterogeneity of HCC candidates according to their
tumour stage/liver functional impairment and the variable
duration of the waiting times throughout the world. This
stratification allows the reader to identify into which scenario
theirpatientfitsandthususetheobtainedoutputsforrational
clinical decision making and also to correctly allocate health
care resources in the management of this complex disease.
PATIENTS AND METHODS
Design of the study and Markov multistate transition
model
We analysed the cost effectiveness of applying resection or
percutaneous ethanol injection (PEI) versus standard man-
agement in cirrhotic patients with early HCC on their
inclusion on the waiting list for OLT. A Markov multistate
transition model was developed to estimate the impact of
treatment on the probability of being transplanted, overall
outcome, and cost effectiveness. A commercially available
software product (Data 3.5;Tree Age Software, 1998, William-
stown, Massachusetts, USA) was used to generate the model
and to tabulate all costs accrued in each group. The study was
performed according to the recommendations of the Panel of
.............................................................
Abbreviations: CEA, cost effectiveness analysis; HCC, hepatocellular
carcinoma; OLT, orthotopic liver transplantation; RCT, randomised
controlled trial; PEI, percutaneous ethanol injection; RF, radiofrequency;
LE, life expectancy; MCYLS, marginal cost per year of life saved.
See end of article for
authors? affiliations
.......................
Correspondence to:
Dr J M Llovet, BCLC Group,
Liver Unit, IDIBAPS,
Hospital Clínic, c/Villarroel
170, 08036-Barcelona,
Catalonia, Spain;
jmllovet@clinic.ub.es
Accepted for publication
29 March 2001
.......................
123
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Cost-effectiveness in Health and Medicine of the US, and fol-
lowing their indications in reporting cost effectiveness analy-
sis (CEA).
19 20
Target population and adjuvant treatments
The study focused on HCC candidates for OLT as the primary
treatment option. This target population included patients
withearlyHCC(singletumour<5cmorthreenodules<3cm)
on an otherwise non-advanced liver cirrhosis (Child-Pugh?s A
and B classes) without associated diseases. We did not
consider Child-Pugh?s C class cirrhotic patients with coinci-
dental tumours because their dropout rate is mostly related to
life threatening decompensation of cirrhosis rather than
tumour progression.
Our model considered two reference cases of HCC
candidates for OLT which were stratified according to tumour
stage and liver function impairment.
Reference case No 1 (group 1). Child-Pugh?s A patient with a sin-
gle HCC <5 cm, treated by surgical resection. This treatment
provides an acceptable morbidity and short term mortality.
2?5
Reference case No 2 (group 2). Patients with either a single HCC
<5 cm and Child-Pugh?s B or with three tumours <3 cm. As
these patients are poor candidates for resection due to their
high risk of postoperative decompensation with associated
death, they were considered for PEI.
PEI is a highly effective option that provides complete
necrosis in 70?80% of cases in tumours smaller than 3 cm.
21?24
Thistreatmenthasbeenwidelyassessedthroughouttheworld
over the last decade, with a safety profile and a low risk of
tumour seeding along the needle tract (0.6% cases per patient;
0.08% per session).
25
Percutaneous radiofrequency (RF)
ablationwasnotconsideredinthemodelbecausereliabledata
on antitumoral usefulness and cost have not been completely
established.In addition,we have recently reported a notewor-
thy rate of needle track seeding related to this procedure,thus
increasing the concerns regarding its application prior to
OLT.
26
Chemoembolisation was also not considered because of
its lower antineoplastic effect if compared with surgery or
percutaneous ablation, and because of the lack of prospective
data showing a beneficial effect. Patients in the control arm
were considered to receive no specific antineoplastic treat-
ment,which represents the standard management of patients
on the waiting list of our transplantation programme to
date.
47
Decision tree and states of health
A diagram of the event pathway is depicted in fig 1. Analysis
of the state of health was performed in three month cycles
starting from inclusion of patients onto the waiting list until a
time period of 10 years after OLT. In summary, patients with
early HCC were allocated to receive adjuvant treatment
according to their risk group or standard management on
inclusion onto the waiting list. Patients of reference case No 1
underwent resection and entered the waiting list state. Three
transition states were considered thereafter:(a) receiving OLT
and entering the post-transplantation state; (b) developing
any contraindication for OLT and entering the dropout state;
or (c) dying of tumour progression or complications of cirrho-
sis. Similarly, patients of reference case No 2 received PEI
treatment and entered the waiting list state where the same
three transition states were considered.Finally,patients in the
non-treatment arm directly entered the waiting list state
without antitumoral treatment where the three transitional
states were again considered.Patients effectively transplanted
entered the post-transplantation state until death.
Summary of data and assumptions
Survival and recurrence on the waiting list
Data and assumptions used in the decision analysis for the
reference cases are depicted in table 1. In Child-Pugh?s A
patients with a single HCC, the probability of survival after
resection was considered to be 93% and 75% at one and two
years, respectively. Recurrence rate at two years was 30%.
3?5
Complete response after PEI was related to tumour size, and
ranged from 80% for single tumours <3 cm, 50% for tumours
of3?5cm,to40%forpatientswithuptothreenodulessmaller
than 3 cm.
21?24
Survival outcome after PEI varied according to
achievement of a complete and maintained response, and
ranged from 62% to 72% at two years.The two year recurrence
rate?new tumour development?was considered to be
25%.
21?24
Survival data for the non-treatment arm were derived from
prospective studies on the prognosis of patients diagnosed
with asymptomatic HCC without vascular invasion or
extrahepatic spread: one and two year survival rates of 80%
and 65%, respectively.
27
Mortality of these patients is due to
HCC itself, and eventually to complications of cirrhosis. Age
related mortality in the periods of time considered was negli-
gible.
Dropout rate
Data on dropout rate of HCC candidates for OLT are rarely
reported. We reported a 23% dropout rate on a six month
median waiting list
4
whereas other authors have described
even higher incidences of 30?40% while waiting for more than
one year.
911
In our model, exclusions from the waiting list
included both death or OLT, contraindications derived from
tumour progression (vascular invasion, lymph node involve-
ment, or metastases), or liver functional impairment (that is,
progressive hepatorenal syndrome).
The probabilities for dropout rate assumed in the model are
summarised in table 1. For the treated groups, values were
derived from probabilities of survival and recurrence after
resection and PEI. Patients who presented recurrences were
consideredforexclusionwhentheydevelopedmajorcontrain-
dications. Data for the non-treatment arm were derived from
the reported probability of tumour progression,vascular inva-
sion, and extrahepatic spread, taking into account that HCC
progression does not always prompt exclusion from the list.
Once exclusion of the list had occurred, median survival was
modelled to be less than one year.
27
Outcomes of patients effectively transplanted were ob-
tained from the best results of groups applying restrictive
selection criteria. In the reference case, five year survival after
OLT and recurrence rate were 70% and 10%, respectively.
4 6?8
Sensitivity analysis
As previously described, for the two reference cases the prob-
abilities of survival during the waiting list (with or without
Figure 1 Diagram of the event pathway: decision tree and states
of health.
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124 Llovet, Mas, Aponte, et al
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treatment), dropout rate, and survival after transplantation
are shown in table 1. The sensitivity analysis was applied to
test different degrees of estimates of the various probabilities
used.
19 20
Establishment of two strata represents a type of sen-
sitivity analysis of the scenarios that are faced in the clinical
setting. None the less, additional sensitivity analyses were
performed varying the main probabilities of outcomes over
clinically relevant ranges.
Variables modelled in the sensitivity analysis included the
dropout rate and outcome after OLT.
(1) Variations in the dropout rate. (a) Best scenario: treatment
achieves a relative reduction of 20% in the dropout rate from
the reference case of the treatment arm. (b) Worst scenario:
treatment achieves a relative increase of 20% in the dropout
rate from the reference case of the treatment arm.
(2) Variations in outcome of transplantation. Survival after OLT
was modelled to include a five year survival rate as low as 50%
as the worst scenario.
Costs
Economic costs were assessed from the payer?s perspective,
and included direct costs of procedures and treatments,
expressed in 1999 US dollars, and were obtained from the
current payments within the Spanish Health Care System
(table 2). These cover the cost of salaries for physicians,
surgeons, and support personnel, equipment, supplies, and
organisational costs. Direct non-medical costs incurred by
patients and their families, as well as indirect costs, were not
assumed in the analysis. Future costs and benefits were
discounted at a baseline rate of 3%.
19 20
Estimates of effectiveness and cost effectiveness
We considered a 10% increase in the probability of being
transplanted as clinically relevant. Effectiveness was
measured as net gain in life expectancy (LE),and according to
recent proposals we defined an increase of at least three
months in LE as clinically relevant.
28
Although quality of life is
an important outcome in calculating cost effectiveness,
reliable data on HCC patients waiting for a liver donor are not
available and thus this analysis was not addressed.
29
The mar-
ginal cost of the treatment strategy was divided by its
incremental benefit,as measured by gain in LE.This results in
a marginal cost per years of life saved (MCYLS) and we have
Table 1 Summary of assumptions used in the Markov analysis
Actuarial survival (months)
Variable 6 12 18 24
Surgical resection*
Actuarial probability of survival 93% 93% 83% 75%
Actuarial probability of dropout 8% 10% 17% 30%
Actuarial probability recurrence 9% 19% 25% 30%
Three month related mortality?4%
Percutaneous treatment**
Actuarial probability of survival 95% 86% 76% 65%
Actuarial probability of dropout 10% 20% 35% 50%
Actuarial probability recurrence 7% 18% 21% 25%
Complete response
Single HCC <3 cm?80%
Single HCC 3?5 cm?50%
Three nodules <3 cm?40%
Natural history*/**
Actuarial probability of survival 97% 80% 72% 65%
Actuarial probability of dropout
Group 1 7% 15% 30% 50%
Group 2 18% 36% 50% 70%
Probability of growth of main nodule, 1 year?70%
Probability of vascular invasion, 1 year? 21%
Probability of extrahepatic spread, 1 year?9%
Liver transplantation
Global outcome after OLT, 5 year survival?70%
Probability of recurrence, 5 year?10%.
Three month related mortality?2%
Probability of survival after dropping out while on the waiting list according to the study groups
Group 1 60% 40% 32% 16%
Group 2 40% 20% 10% 0%
*Reference case No 1 (group 1).
**Reference case No 2 (group 2).
Table 2 Direct costs for procedures and treatments
Variable
Mean
baseline cost
(US$)
Direct cost of procedures
Analytical data and imaging techniques
Analytical data (including AFP) 80
Doppler ultrasound 113
Spiral computed tomography scan 266
Bone scintigraphy 100
Treatments
Surgical resection 13 330
Percutaneous ethanol injection 3990
Orthotopic liver transplantation 73 330
Follow up while on waiting list
After resection
First year 1000
Second year 4000
After percutaneous ethanol injection
First year 4830
Second year 9330
After dropout
First year 8130
Second year 13 065
Follow up after OLT
First year 26 660
Second year and thereafter 13 330
Outcomes
HCC related terminal care 6660
Death after OLT 13 330
OLT, orthotopic liver transplantation; HCC, hepatocellular carcinoma.
Cost effectiveness of adjuvant therapy for HCC prior to OLT 125
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applied the conventional threshold of $50 000 per year of life
saved as the accepted cut off value to consider an intervention
?cost effective?.
30?34
RESULTS
Probability of being transplanted and overall survival
The probability of being transplanted and the overall survival
are depicted in figs 2 and 3. Surgical resection increased the
transplantation rate from 3.7% to 10.7% for waiting lists of six
and 24 months,respectively.The seven year probability of sur-
vival increased for patients undergoing resection compared
with standard management, and was higher than 10% for
waiting lists exceeding one year. Percutaneous treatments
increased the probability of being transplanted and the seven
year survival in all waiting times.These benefits became clini-
cally relevant when the waiting time exceeded one year.
Cost effectiveness
The results of the CEA are shown in figs 4 and 5, and table 3.
Resection provided a clinically relevant net gain in LE ranging
from 4.8 to 6.1 months if waiting times exceeded six months.
The CEA shows that the MCYLS was less than $40 000 for lists
of 12?24 months. Ethanol injection achieved a clear gain in
LE, ranging from 5.2 to 6.7 months, increasing according to
the length of the waiting list. Its cost effectiveness ratio was
less than $23 000/year of life saved (fig 5). Undiscounted
results did not statistically differ from those discounted at 3%.
Sensitivity analysis
The results of the sensitivity analysis are shown in table 4.Our
model was most sensitive to variations in the dropout rate and
survival after OLT. When assuming the highest benefit as a
result of treatment (best scenario: relative decrease of 20% in
dropout rate), gains in LE were relevant (resection 3.3?8.3
months; PEI 6.8?9.1 months), with a cost effectiveness ratio
always below $60 000/year of life saved. When considering
scenarios of poor outcome after resection (worst scenario:
relative increase of 20% in dropout rate), this treatment
provided a minimal benefit in LE, with a marginal cost rang-
ing from $135 600/year of life saved (six month waiting list) to
$43 650/year of life saved (24 month waiting list). Conversely,
even in this worst scenario, PEI offered gains in LE always
exceeding three months, with a marginal cost per year of life
of less than $32 000.
Assuming a 50% five year survival rate after OLT (worst sce-
nario), the estimates of LE decreased in all cases. For this sce-
nario, PEI retained a cost effectiveness ratio for all waiting
times but resection was cost effective only for waiting times
exceeding two years ($43 074/MCLYS).
Figure 2 Probability of being transplanted (A) and seven year
intention to treat survival (B) comparing patients with hepatocellular
carcinoma undergoing resection versus conservative management
while on the waiting list for liver transplantation.
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Figure 3 Probability of being transplanted (A) and seven year
intention to treat survival (B) comparing patients with hepatocellular
carcinoma undergoing percutaneous treatment versus conservative
management while on the waiting list for liver transplantation.
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Figure 4 Cost effectiveness analysis of surgical resection for
hepatocellular carcinoma versus conservative management while on
the waiting list for liver transplantation. Cost effectiveness ratio and
marginal effectiveness in terms of gains in life expectancy are shown
according to length of waiting time.
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Figure 5 Cost effectiveness analysis of percutaneous treatments for
non-surgical hepatocellular carcinoma versus conservative
management while on the waiting list for liver transplantation. Cost
effectiveness ratio and marginal effectiveness in terms of gains in life
expectancy are shown according to length of waiting time.
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DISCUSSION
The excellent results of liver transplantation for early HCC are
curtailed by the increasing dropout rate while waiting for a
donor, thus worsening outcome when analysed on an
intention to treat basis.
14
Several strategies have been
postulated to decrease the impact of exclusions. Living donor
liver transplantation, domino and split liver transplantation,
as well as use of marginal livers are policies currently applied
in some transplant units. A decision analysis has recently
shown that living donor liver transplantation compared with
OLT is cost effective for early HCC for waiting times exceeding
seven months.
35
However, implementation of these strategies
is complex, and will probably be restricted to leading
transplant units.This has led most centres to administer anti-
tumoral treatments on entering HCC patients onto waiting
lists.
13?18
The benefits of this policy are unknown as prospective
RCTs in the field are lacking and they are seen as almost
unfeasible due to the cost, heterogeneity, and complexity of
the medical interventions. This uncertainty prompted us to
conduct a decision analysis to address the clinical benefits and
cost effectiveness of adjuvant treatment.
The model applies the best curative therapies available for
the selected strata of HCC candidates for OLT and considers a
waiting time between six and 24 months. This strategy
predicts moderate gains in LE in almost all cases,and the gain
remains below the accepted cost effectiveness ratio ($50 000/
per year of life saved).
30?34
In fact, it compares favourably with
accepted medical interventions, such as implantable
cardioverter-defibrillator for coronary heart disease
($26 000?40 000 per year of life) or haemodialysis ($42
000/qualityadjustedlifeyearsaved).
32?34
Surgicalresectionwas
cost effective while waiting for at least one year. After this
time, surgery increased the transplantation rate, with moder-
ate gains in LE and an acceptable cost effectiveness ratio. In
contrast, LE gains and cost effectiveness ratio were less
favourable ($74 000 per year life gained) with shorter waiting
times.There may be some concerns on the applicability of this
invasive therapy while on the waiting list. As an alternative,
primary liver resection and ?salvage OLT? (performed when
recurrence or decompensation after resection occurs) have
been postulated to save organs.
36
We have applied this policy
over the last decade, where resection was considered as the
firstline option,but unfortunately less than 10% of candidates
benefited.
1
Surgery is feasible for patients with preserved liver function
andsingletumoursbutitistooriskyinsubjectswithimpaired
hepatic function and/or multiple HCC sites.
2?5
Their high mor-
bidity and mortality impede any benefit of surgery. Accord-
ingly, these patients were modelled to receive percutaneous
treatment, which was identified as cost effective in all
scenarios. It could be argued that PEI is not the sole effective
therapy for non-surgical HCC and that other widely used
alternatives such as RF thermal ablation,
26 37
chemo-
embolisation,
13?18
or even chemotherapy
38
could be modelled.
Ethanol injection is a safe,cheap,and effective treatment that
achieves a 40?80% response for patients with small HCC
21?24
and the available studies provide robust information for deci-
sion analysis. RF thermal ablation as a primary treatment for
HCC may have similar efficacy.
37
Compared with PEI, its
increased cost and the impact of complications may balance
the benefits of reduced hospital stay. However, we have
recently reported a 10% rate of tumour seeding after RF ther-
mal ablation associated with subcapsular location or an
aggressive tumoral pattern. Therefore, although there are no
studies on its benefit when applied during the waiting list,we
discouragethisprocedurepriortoOLT.
26
Finally,chemoemboli-
sation is the standard antitumoral treatment for HCC prior to
OLT in most transplant programs. Its antitumoral effect, even
when using high dose chemotherapy, is less than that of PEI,
and despite the fact that some authors have suggested
benefits in patients with a favourable response to therapy
(downstaging),
13
there are no RCTs showing the benefit of this
strategy. In addition, studies assessing this point have not
identified a difference in tumour recurrence and survival
attributable to therapy.
The sensitivity analysis disclosed that ethanol injection was
beneficialandcosteffectiveinallrangesusedbutthebenefitsof
resection decreased when varying the assumptions of the
model.Intheworstscenariosfordropoutrateandsurvivalafter
OLT(fiveyearsurvival50%),resectionprovidedpoorgainsinLE
regardless of the length of the waiting list, with an expensive
cost effectiveness ratio.These controversial benefits may be rep-
resentative of transplantation centres achieving poor results
after surgery as a consequence of both limited technical skills
and expertise of the group. In support of this, it has recently
been reported that OLT centres in the USA that perform less
than 20 transplantations per year have mortality rates higher
than those at larger centres.
39
Thus decision makers should con-
sider these data to warrant implementation of economic
resources for the most efficient groups. As done for most
decision analyses,we used local costs for cost effectiveness esti-
mations. However, it is clear that health costs in Southern
Europe are lower than in Northern countries or even in the
USA. Accordingly, in areas where local economics are largely
higher,the cost effectiveness of some scenarios may be lost.
The current analysis was limited by the scarcity of data on
exclusions during the waiting list. For untreated patients we
have assumed a dropout rate ranging from 15% to 36% at one
year of waiting time, for the two reference cases. In the sensi-
tivity analysis, these values varied by 20% up/down in the
Table 3 Cost effectiveness analysis of
performing adjuvant therapy according
to risk group and length of waiting list
Risk
group
Waiting list
scenario
GaininLE
(months)
MCYLS
(US$)
Group 1 6 m 2.2 74 728
12 m 4.8 38 117
18 m 5.9 32 886
24 m 6.1 32 060
Group 2 6 m 5.2 16 442
12 m 6.5 12 489
18 m 6.7 10 911
24 m 6.4 10 086
MCYLS, marginal cost per year of life saved.
Table 4 Sensitivity analysis for the best and worst
scenarios of dropout rate and survival after orthotopic
liver transplantation (OLT) according to risk group and
length of waiting time (range 6?24 months)*
Scenario
GaininLE
(months)
MCYLS
(US$)
Group 1
Best dropout rate** 3.3?8.3 54 291?27 362
Worst dropout rate*** 1.1?4.2 135 639?43 650
Five year survival after OLT (50%) 1.5?4.6 103 007?43 074
Group 2
Best dropout rate** 6.8?9.1 16 536?11 690
Worst dropout rate*** 3.8?4.3 19 593?10 509
Five year survival after OLT (50%) 2.0?4.7 42 105?13 824
*All results are expressed according to the waiting time range: the
first figure corresponds to six months?the last figure corresponds to
24 months of waiting time.
**20% decrease in dropout rate compared with reference case, as a
result of treatment
***20% increase in dropout rate compared with reference case,
despite treatment.
MCYLS, marginal cost per year of life saved.
Cost effectiveness of adjuvant therapy for HCC prior to OLT 127
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best/worst scenarios. These assumptions were derived from
our reported data on exclusions, and are in accordance with
recent 1999 data from the UNOS, where patients removed
from the list due to death or other reasons in the USA ranged
from 26% to 41%.
9
Insummary,ourstudyindicatesthatadjuvanttreatmenton
entering HCC patients onto a waiting list for OLT is cost effec-
tive and recommended in almost all scenarios. Patients with
well preserved liver function and a single HCC, waiting for at
least one year, may benefit from surgical resection but for
shorter waiting times the economic investment is controver-
sial. In non-surgical patients, percutaneous treatments are
cost effective in all waiting times and thus their application is
warranted.
ACKNOWLEDGEMENTS
Supported by grant SAF 004-98 from the Comisión Interdepartamen-
tal de Ciencia y Tecnología, and a grant from the Fundació La Marató
TV3, 1999.
.....................
Authors? affiliations
J M Llovet, J Fuster, M Navasa, J Rodés, J Bruix, Barcelona-Clínic
Liver Cancer (BCLC) Group, Liver Unit, Institut d?Investigacions
Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, University of
Barcelona, Catalonia, Spain
X Mas, J J Aponte, Epidemiology-Biostatistics Unit, Institut
d?Investigacions Biomèdiques August Pi I Sunyer, Hospital Clínic,
University of Barcelona, Catalonia, Spain
E Christensen, Clinic of Internal Medicine, Bispebjerg University
Hospital, Copenhagen, Denmark
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doi: 10.1136/gut.50.1.123
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J M Llovet, X Mas, J J Aponte, et al.
 
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