SHORT REPORT

Transplantation for Alcoholic Liver Disease:Report of a Consensus MeetingKerry Webb,1 Liz Shepherd,2 Ed Day,3 George Masterton,4 and James Neuberger1

1Liver Unit, University Hospitals, Birmingham, United Kingdom; 2Liver Unit, Royal Free Hospital, London, UnitedKingdom; 3University of Birmingham, Birmingham, United Kingdom; and 4Liver Unit, Edinburgh RoyalInfirmary, Edinburgh, United Kingdom

Received November 7, 2005; Accepted November 17, 2005.

A one-day consensus meeting was convened at theClinical Research Facility in Birmingham on 19 Novem-ber 2004. The group sought to include representativesfrom the eight UK and Eire liver transplant units and inthe event received 28 delegates from seven units.

The purpose of the group was to look at issues re-garding the transplantation of patients with alcoholicliver disease (ALD) primarily from a psychosocial andaddiction perspective rather than from a physical one.The group hoped to define some of the issues and di-lemmas that surround the decision to transplant theALD patient in an era of donor shortage, paying partic-ular attention to the issue of return to alcohol usepost-transplant.

OVERVIEW OF THE ISSUES (KERRY WEBB)

Transplantation for liver disease has been an ac-cepted treatment option for many years. Where thecause of the liver disease is alcohol induced (ALD)there has increasingly been a tendency to considertransplantation despite the cause of the disease oftenbeing viewed in the wider domain as “self-induced”.Indeed, according to the British Liver Trust records,between 1996 and 2000 inclusively, 13.8% of alltransplants (468/3400) were for ALD. In an era ofdonor shortage, however, there is always a concernthat organ utility is as successful as possible.1 Thiscan surely not be the case where patients with ALDdemonstrate a risk (perceived or real) of returning toalcohol use post-transplant. The difficulty has alwaysbeen trying to identify those at risk of relapsing toalcohol use post-transplant as well as defining ex-actly what constitutes a relapse. Does it mean thereturn of the behaviour (alcohol consumption) that

led to the onset of ALD in the first place or does itmean the return of medical pathology, indicatingdamage to the graft? In the addiction field, return toalcohol after a period of abstinence can be defined aseither a lapse (slip) or a relapse, depending onwhether the use was a one-off episode or a moreprolonged period of alcohol use. In studies looking atrecidivism post liver transplant, there is no such clar-ity and thus a transplant patient consuming a singleglass of champagne at their daughter’s wedding 10-years post transplant is often classified along with thepatient who returns to dependent alcohol use imme-diately post-transplant. It would be unlikely that theformer patient would in any way insult their graftthrough a single unit of alcohol, whereas the latterpatient is at grave risk of either direct damage to thegraft or indirect damage through, for example, theresumption of alcohol problems leading to compla-cency and non-compliance with the transplant fol-low-up programme.

The transplant unit has a responsibility not only toexplore the issues of transplantation for ALD but alsoto understand their own motives and examine theirown view point in the role of transplanting for ALD.The transplant team has to not only consider theneeds of the patient but also the needs of each patienton the transplant waiting list at any one time, asoffering a graft to one patient as it becomes availablemight mean another patient dying before a furthersuitable graft becomes available. The team also has aduty to understand its own prejudices, positive ornegative, toward transplanting “the alcoholic”. Fi-nally, the team might also perceive a need to considerthe public examination of their use of organ donation.

Address reprint requests to Kerry Webb, RMN, Liver Unit, Queen Elizabeth University Hospital, Edgbaston, Birmingham, Birmingham B13 9DP,United Kingdom. Telephone: 44-121-627-8762; FAX: 44-121-627-8762; E-mail: kerry.webb@uhb.nhs.uk

DOI 10.1002/lt.20681Published online in Wiley InterScience (www.interscience.wiley.com).

LIVER TRANSPLANTATION 12:301-305, 2006

© 2006 American Association for the Study of Liver Diseases.

If the public perception is such that they believe thatuse of the donated graft is ill-advised or wasteful, willthey be less likely to donate and thus impact nega-tively upon the overall size of the national transplantprogramme? It is important, however, to inform thepublic rather than just respond to their reaction.Indeed studies have been conducted that show thatthe public may be likely to make decisions about howto utilise organs based on empathic responses ratherthan objective ones would be likely, in turn, to makeless effective use of available organs.2

MEDICAL ASPECTS IN THE ASSESSMENT OFPATIENTS WITH ALCOHOLIC LIVER DISEASEFOR TRANSPLANTATION (JAMESNEUBERGER)

In general, indications and contra-indications for livertransplantation in those with ALD are similar to thosebeing assessed for transplantation for other indica-tions; however, additional considerations apply to thework-up of such patients in addition to the assessmentfor the reasons for alcohol excess and estimations of theprobability of the person returning to alcohol consump-tion.3

The effect of abstinence is often uncertain. Indeed, aproportion of patients with ALD may improve with ab-stinence to such an extent that transplantation is nolonger indicated or can be deferred.4 While the full ef-fects of abstinence may take up to 18 months to achievethe maximum effect, in practice, for those with ad-vanced disease, it is often very difficult to predict theextent of hepatic recovery, and the patient may requireclose monitoring to ensure that the timing of transplan-tation is appropriate.

Extra-Hepatic Alcohol Damage

Alcoholic damage is not confined to the liver andevidence of other organ damage must be considered.It is common practice to evaluate cardiac function(with imaging and stress tests),5 although the extentto which cardiac impairment may prejudice success-ful outcome remains uncertain. We also will considerbrain scanning (usually with CT scanning) to look forevidence of structural brain damage, but again, thereis relatively poor correlation between structure andfunction. A neuropathy (autonomic, sensory, or mo-tor) may indicate a less good outcome but this has notbeen conclusively shown.

Post-transplant, there is a higher incidence of malig-nancy, especially of the head and neck and oesopha-gus.6 It is prudent therefore to ensure that early can-cers in these areas have been excluded as far as ispossible. The extra cancer risk may be related to smok-ing rather than alcohol.

Finally, alcoholic liver disease may be associatedwith other causes of liver damage, such as hepatitis Bor C viral infection, obesity, and other drug toxicity.7

DEFINING THE NON-MEDICAL ASPECTS INTHE ASSESSMENT OF PATIENTS WITHALCOHOLIC LIVER DISEASE FORTRANSPLANTATION (LIZ SHEPHERD)

When considering the non-medical issues in transplan-tation for ALD, these can broadly be split into thoserelated to assessment of the patient and those related tothe treatment and follow-up of the patient post-trans-plantation.

When assessing the patient, there needs to be a com-prehensive assessment of their alcohol and illicit sub-stance (mis)use history, as well as the physical, psycho-logical, forensic, and social consequences of this.8 Inperforming this assessment, it is acknowledged thatclinicians might want to focus on the absolutes, such aslength of abstinence from alcohol. However in the ab-sence of an absolutely reliable test for sporadic alcoholconsumption, even this can be difficult to monitor andprove without doubt.9 It is also important to note thatabstinence is usually in the context of deterioratinghealth, often precipitating lengthy hospital stays; thuspre-transplant abstinence cannot be seen as an abso-lute predictor of abstinence post-transplant.5 Giventhat some patients may need to be listed for transplan-tation before they are able to prove their abstinence,serious consideration needs to be given to this issue.On completion of the assessment it may be possible torate the patient as low, medium, or high risk (after Gishet al., 2001)8 for relapse, but should we consider trans-planting high risk patients given the shortage of do-nors?10

When considering these issues, clinicians have tothink about the purpose of assessment, whether theinformation gained is to inform treatment for the pa-tient’s alcohol problem or whether the information isused as part of a screening mechanism. Either way, theassessors, be they specialist nurse or psychiatrist, haveto acknowledge the conflicting issues of gaining infor-mation that may inform the team but potentially reducethe patient’s chance of being listed.

Looking at the issues in treatment post-transplanta-tion the survival of both the graft and patient is para-mount. Abstinence is the aim, as supported by sub-stance misuse models of practice for alcohol-dependentpatients. However, not all patients transplanted forALD are dependent on alcohol,9 and some do return todrinking at low levels that do not appear to harmthem.11 If this happens, should we persist with theabstinence message or satisfy ourselves that a harmminimisation message is acceptable? When thinkingabout this, we need to acknowledge that patients talk toeach other and may decide to drink based on theirperceptions of other patients’ behaviours and health. Inproviding treatment and follow-up for this patientgroup, the emphasis needs to be on the long term, giventhat lapse/relapse can often happen some years post-transplant.12 If we accept this, then we need to thinkabout who provides this follow-up, for how long. and inwhat context, given that substance misuse provision,

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and models of practice, vary across the country. Thismay limit local support to short-term follow-up ratherthan long-term relapse prevention, which runs con-trary to evidence that suggests that in some cases re-lapse may occur some years post-transplant.12

There are other issues that need to be addressed thatfollow on from this discussion. If clarity and consis-tency of approach is addressed with ALD, then what ofsmoking, obesity, non-compliance (as in teenagers withauto-immune hepatitis), and transplantation for pa-tients on Methadone.13 Likewise when the patient pre-sents with a mixed aetiology, e.g., alcohol withhaemachromatosis, HCV, alpha-1 anti-trypsin defi-ciency, or hepatocellular carcinoma the picture is oftenmore complex.

Perhaps when considering these issues around livertransplantation for ALD there are more questions thananswers? Although this may be the case, informed dis-cussion based on the evidence currently availableneeds to occur to ensure best possible use of donatedorgans and increased trust in the transplantation pro-cess on the part of the general public.

THE ISSUE OF ALCOHOL USE POSTTRANSPLANT (ED DAY)

The prognosis for cases transplanted for ALD is roughlythe same as that for non-ALD cases, but in an era oforgan shortage, the procedure remains controversial. Akey issue is the likelihood of relapse and its influenceon outcome. Abstinence from alcohol is considered im-portant for compliance with medication and follow-upprotocols, avoiding the development of new or pre-ex-isting extra-hepatic alcohol-induced organ damage, orthe development of alcohol-induced liver damage in theallograft.12

There are still many unanswered questions about theclinical course of alcohol problems. The few long-termfollow-up studies of untreated populations have sug-gested that possible outcomes of a diagnosis of alcoholdependence include stable abstinence, a return to con-trolled asymptomatic use, continued misuse, or prema-ture death.14–16 A few individuals maintain a relativelystable pattern of intermittent alcohol misuse withoutdependence from a young age, but in general, thisgroup have fewer substance-related problems, do notdevelop physiological dependence, and manifest fewerrisk factors. However, in general alcohol dependence(as opposed to misuse) is a relapsing and remittingdisorder. Several studies indicate that only about 2% ofall individuals with a diagnosis of alcohol dependenceachieve stable abstinence each year, with or withouttreatment.16 Mann et al. (2005) recently found thatalthough 27% had died, 40% of patients were abstinent16 years after a 6-month treatment programme, and55% of these had been continuously abstinent since theindex treatment episode.17 If this is the case, how longshould abstinence from alcohol use persist before sub-sequent relapse is deemed unlikely? After 2 years ofabstinence, 40% of alcoholics will eventually relapse,but after 5 years of abstinence relapse is relatively un-

likely.18 Vaillant concludes that, analogous to cancerpatients, a follow-up of 5 years rather than 1 or 2 yearsis necessary to determine stable recovery.15 Thisshould be contrasted with the 6-month abstinence rulesuggested by some transplant guidelines.19

An improved knowledge of the predictors of relapsewould help the assessment and possibly also refineattempts at treatment. However, studies in the livertransplant population have led to contradictory results,with no reliable predictive factors identified.20 Thesestudies are beset by a number of methodological prob-lems, not least that a variety of definitions of relapse areused, making the results hard to compare.21,22 Fur-thermore, most studies are retrospective case note re-views with inconsistent methods of assessing the leveland severity of alcohol problems before transplanta-tion. Follow-up periods have usually been too short toprovide meaningful information about relapse, and in-vestigators have seldom been independent of the trans-plant team.

Despite these difficulties, the reported relapse ratesof between 10 and 50% are lower in this group than thegeneral alcohol dependent population. Vaillant’s long-term follow-up work has suggested four key factors thatmight predict good outcomes for heavy drinkers, andthese were backed up by other work on remission fromaddictive behaviours.23

1. Compulsory supervision or experiencing a consis-tent aversive experience related to drinking,

2. Finding a substitute dependency to compete withalcohol use,

3. Obtaining new social supports, and4. Inspirational group membership (e.g. Alcoholics

Anonymous).

Membership of Alcoholics Anonymous provides eachof the four components, but they are also present in theexperience of liver transplantation. The transplant andthe subsequent need for daily immunosuppressivedrugs for the rest of the subject’s life provide a constantreminder of the dangers of relapse to alcohol misuse.Frequent follow-up by a team of experts also providesadditional community supervision. Dependence on theliver team’s continued care and the group supportamong transplant survivors is analogous to depen-dence on the comfort provided by self-help groups. Be-ing given a new life and an expensive operation may beanalogous to a “born again” religious experience. Fi-nally, the OLT survivor becomes intimately involvedwith a health care team unscarred by their past misuseof alcohol and filled with hope for the future.18

Therefore, although the research evidence base forthis group is still developing, there is evidence thatsuggests that carefully selected alcohol-dependent pa-tients with ALD can have a good outcome in terms ofgraft survival and relapse to alcohol use post-operation.

EQUITY OF ACCESS (GEORGE MASTERTON)

Patients in the UK should have a right to be assessed forliver transplantation on the same basis irrespective of

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which unit they attend. This universality should bereadily achieved when the disease is an uncontroversialindication, runs a predictable course, and is not asso-ciated with multi-system pathology. However it be-comes more difficult when these conditions do not ap-ply, added to which with ALD, hostile public attitudescomplicate the picture.2

There is a consensus that it is unethical to regardALD as an absolute contraindication, given the post-transplant outcome, to 5 years at least, is as good if notbetter than for most other aetiologies. Supporting thisposition, following a liver transplant, recurrent ALD israre while few patients die of an alcohol-relatedcause.24 Lastly, ALD is essentially diagnosed by exclu-sion of other causes married to a credible history ofalcohol misuse: it is not an infallible diagnosis, having afalse positive rate in our unit of 5%, and as much as13% in one American series.25 Given this, it might beargued that ALD patients should not be assessed dif-ferently from any other candidates, but irrespective ofpublic policy considerations, it is surely as important totake into account the aetiology and management of thecausal factor when it is alcohol abuse as for any othercause of liver disease.

Regarding ALD as an absolute contraindication ordisregarding the alcohol aetiology altogether would en-able equity to be achieved more readily than the currentapproach of selection among ALD patients, involving anadditional hurdle of an assessment of the drinkingproblem. As there is no standardised approach to eitherthis process or its goal(s), equity is most improbable,i.e., a patient regarded as unsuitable for transplantbecause of their alcohol history in one UK unit might belisted by another.

Because of organ shortages, selection for liver trans-plant is based on a utilitarian philosophy: no patienthas a preordained right to a graft.26 In practice, thismeans identifying the hosts who will give grafts thelongest and healthiest “lives”. Cohort outcome studiesprovide the evidence for determining this, with durationof survival being the primary endpoint. When selectingamong ALD patients there is a second key end point,which is relapse drinking.24 However, because researchhas concentrated on “any drinking” as the outcomevariable rather than harmful or dependent drinking,the endpoint is not utilitarian in terms of predictingsurvival. This focus has raised concerns that patientswho are removed from liver transplant waiting listsbecause of an alcohol “slip” are being managed uneth-ically,27 and transplantation is wrongly regarded as afailure if the patient drinks little and occasionally with-out any harm.28

To be just and equitable, predicting relapse as a se-lection criterion should be employed for a demonstrablyutilitarian purpose, which implies identifying likely re-current harmful or dependent drinking, or to advise thetransplant team which ALD patients would be unlikelyto cooperate with treatment in the event of relapsedrinking. Any predictor should affect outcome, and dis-criminate consistently and well: if no predictors cansatisfy these requirements, this strategy be abandoned.

Further research should be refined to evaluate theusefulness of predictors that are intrinsically fair, ob-jective, and reliably assessed in determining whateverkey, utilitarian endpoint with regard to relapse alcoholuse is agreed by the transplant community to be mostappropriate.

SUMMARY OF CONSENSUS MEETING

It is clear that liver transplantation has become a recog-nised and accepted form of treatment for those withend-stage ALD. The evidence base to date suggests thatprognosis for survival at 5-years post-transplant isgood and that alcohol-related graft damage post-trans-plant is relatively low. Despite this knowledge, the gen-eral public continue to hold reservations about the useof donated livers for those with “self-inflicted” injurysuch as “alcoholics“.2 Such debate will always be voicedin an era of donor shortage when those with ALD areparticularly singled out. There has been less focus ofattention toward those with recurrent hepatitis C (HCV)following transplantation, perhaps for intravenousdrug use, despite the greater significance of graft loss at5-years post-transplant.29 There is also less attentiongiven to obese patients with non-alcoholic fatty liverdisease, or teenagers re-grafted following non-compli-ance.

The lack of quality prospective and longitudinal re-search data on ALD and recidivism post transplant hasbeen highlighted above, and the study group is activelywelcoming such research into the arena. However, evenless work has been done to tackle the lack of consistentapproach both intra- and inter-transplant unit. Suchwork would be a valid study in itself. Furthermore, littleis known about the process of selection of candidates atlocal liver units for referral on to the transplant assess-ment teams, which must again question what factorscontrol the selection of assessment candidates.

In addition to the question as to “What is relapse?,how much does it occur, and how much does it mat-ter?”, the study group would like to see all supra-re-gional transplant centres demonstrating transparent,measurable assessment processes that sustain an eth-ical service with equity of access based on factors cor-rectly adjudged to select those candidates likely to dowell. Where patients are transplanted outside of inter-unit guidelines, a rationale should be available.

Finally, there may be a need for ALD patients to re-ceive ongoing psychological interventions and supportpost-transplant in order to sustain abstinence and sta-bility post-transplant.30 Once risk factors have beencorrectly assessed, then appropriate treatment andsupport methods can be validated.

LIST OF FOCUS GROUP MEMBERS

Sally Bufton, Liver Transplant Coordinator, Birming-ham; Bob Cramb, Consultant Chemical Pathologist,Birmingham; Ed Day, Senior Lecturer and Consultantin Addiction Psychiatry, Birmingham; George Georgiou,Consultant in Addiction Psychiatry, Birmingham;

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James Neuberger, Professor of Hepatology, Birming-ham; Rebecca Russell, Assistant Research Psycholo-gist, Birmingham; Kerry Webb, Clinical Nurse Special-ist in Addiction Psychiatry, Birmingham; MonicaSmith, Liver Transplant Coordinator, Birmingham;Kate Grainger, Clinical Nurse Specialist in Hepatology,Cambridge; Esther Moore, Liver Transplant Co-ordina-tor, Cambridge; Maxwell Saxty, Clinical Nurse Special-ist in Liaison Psychiatry, Cambridge; Cathy Walsh,Consultant Liaison Psychiatrist, Cambridge; Aoiffe Cof-fey, Liver Transplant Co-ordinator, Dublin; Teresa Mc-Donnell, Social Worker, Dublin; Donna Hill, LiverTransplant Coordinator, Dublin; Louise Learmonth, Al-cohol Liaison Nurse, Dublin; George Masterton, Con-sultant Psychiatrist, Edinburgh; Roger Smyth, Consul-tant Psychiatrist, Edinburgh; Michelle Clayton,Lecturer Practitioner in Liver Care, Leeds; Laura Hud-son, Transplant Co-ordinator, Leeds; Jacqueline Jen-nings, Senior Sister, Leeds; Annette Courtney, LiverUnit Social Worker, Newcastle; Diane Hume, Liver UnitSister, Newcastle; Daren Vernon, Liver Unit ChargeNurse, Newcastle; Katherine Rees, SpR in Psychiatry,Newcastle; Geoff Lloyd, Consultant in Liaison Psychia-try, Royal Free, London; Liz Shepherd, Clinical NurseSpecialist in Alcohol and Liver Transplantation, RoyalFree, London; Dianne Dobson, Acting Liver TransplantCo-ordinator, Royal Free, London.

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