barcelona . spain - European Association for the Study of the Liver

BARCELONA . SPAIN
116 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 117
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
CAN WE OFFER LIVER TRANSPLANTATION TO PATIENTS WITH
ALCOHOLIC HEPATITIS
ANSWER: NO
James Neuberger
Bristol, UK
E-mail: j.m.neuberger@bham.ac.uk
The arguments against the use of livers from deceased donors are summarised below. These arguments
do not express the opinions of the author, the Queen Elizabeth Hospital or NHS Blood and Transplant.
KEY POINTS
• Access to liver transplantation should be based on the transparent criteria of need, benefit,
justice and equity. Those with alcoholic hepatitis (AH) have the same right to be considered for
liver transplantation (LT) as all other patients on the same non-judgemental criteria and without
a need for a fixed, arbitrary period of abstinence.
• While the landmark study from Mathurin shows that transplantation can be done successfully
for highly selected patients with AH, outcomes after transplantation are less good than for other
indications and a significant proportion of those who met the criteria for transplantation will
survive without surgery. These are spared the long-term consequences of immunosuppression
and its associated risks of cancer, infection and kidney failure.
• These observations suggest that transplantation for AH is not an efficient use of scarce
resources and will deprive those patients who will have a better outcome.
• Newer therapies for AH may prove more effective and safer than LT.
• Because there is a shortage of donor livers, clinicians will need to identify those who would
therefore lose access to transplantation if the recipient pool is increased.
• Public opinion is against the use of donated livers for those with alcohol-associated liver
disease so widespread use of donated livers may result in a decrease in donations.
INTRODUCTION
The number of people who would benefit from liver transplantation is considerably greater than the number
of available grafts donated after death. Therefore this scarce resource needs to be rationed. While livers
can be allocated using a number of different approaches (such as need, benefit or utility), it is also essential
that donated livers are allocated according to a process that is objective, transparent and just. Although
allocation models vary between jurisdictions, all models include elements of benefit and need.
Allocation of donated livers to those with end-stage liver disease from self-induced habits has long attracted
controversy but it is not the role of the clinician to make value judgements. Allocation of organs to those with
self-induced liver damage (whether from alcohol, drug use or excessive eating) should be based on need
and benefit, as for any other indication.
In those with alcohol-associated liver disease, whether with cirrhosis or acute alcoholic hepatitis, allocation
should be based on:
• Need: will the patient die from liver failure in the absence of transplantation
• Benefit: will the patient have sufficient benefit from the transplant
• Outcome: will the patient comply with the need for follow-up and monitoring
and avoid alcohol excess
NEED AND BENEFIT
Does the patient need a transplant
In many ways the patient with AH should be considered in the same way as the patient with fulminant
hepatic failure (FHF): if the patient survives the initial illness, then survival is likely to be very good and
similar to the normal healthy population, if abstinence is maintained (Sandahl (a)). This contrasts with the
patient with cirrhosis where there is a progressive risk of decompensation, liver cell cancer and death.
Life after transplantation, while usually very good, is not normal in either quality or quantity. Those who
survive the first year have an increased risk of death compared with the age matched population. For
example, UK figures show that a male aged 45 years at transplantation who survives the first post operative
year had a survival reduced by 17 years which represents a 15 year loss of life expectancy. There is an
increased risk of malignancy (at least 2-fold compared with aged and sex matched population), a 2-3 fold
increased risk of death from cerebrovascular and cardiovascular disease, as well as infection and renal
failure. Indeed, in the long term, the risk of renal failure is likely to be even greater in those grafted for AH
since renal impairment is common and pre-transplant renal impairment is good prognostic marker for late
stage renal failure post LT. The quality of life is also reduced with only half returning to work or home-making.
Is a period of abstinence necessary
In many patients with alcoholic liver disease, abstinence is associated with improvement. Often a period
of abstinence is required, not only to assess whether the patient will improve to such an extent that
transplantation is not required but also to explore why the patient has drunk excessively and to put in
place support so the patient will be helped to maintain abstinence. There is little place for a fixed period of
abstinence as there are few data to justify any given period (Brown) and in those with severe disease, such
as AH, death may be the price of proving abstinence. In the UK, there is no requirement for a fixed period.
Will the patient return to alcohol
Despite much public concern, the evidence suggests that a return to a damaging pattern of alcohol
consumption is low: indeed, our own data show that, at 5 years, graft loss from alcohol is similar to that from
recurrent PBC (4%) and considerably less than for HCV infection (25%). Nonetheless, a patient returning to
alcohol does have a major adverse impact on public perception.
Will the patient survive without a transplant
While there are several prognostic models that predict survival of those with AH, these models are relatively
imprecise when applied to the individual (Sandahl (b), Singal). Thus, there is a real risk that transplantation
will be done needlessly and another recipient dies.
Are there other potentially less toxic treatments
There is an increasing number of agents being assessed for those with AH: these include corticosteroids,
anti-TNF, N-acetyl cysteine, oxypentifylline as well as new potential targets such as CXC chemokines, and
osteopontin (Gao, Altamirano). If effective, the patient is more likely to return to a better quality and quantity
of life than with a transplant.
BENEFIT
There have been several case reports showing that liver transplant can be done successfully in alcoholic
hepatitis (Singhal) but the landmark study by Mathurin and colleagues provides the first clear evidence that
there is a survival benefit. While this study shows clearly that transplantation can be offered with survival
benefit to a highly selected group of patients with AH, it does not mean that this scarce resource should be
allocated to this group.
Survival of the transplanted group is less than would be expected in those with cirrhosis or acute liver
failure: current European and US data suggest that survival rates of over 90% should be anticipated at 1