Drug and Alcohol Review (1996) 15, 183-188

FOR DEBATE

The case for liver transplantation in end-stage alcoholic liver disease

ROBERT G. BATEY

Gastroenterology Department, John Hunter Hospital, Newcastle, Australia Abstract

Liver transplantation is now a routine procedure and is seen as a valid treatment option for end-stage liver disease. Alcoholism has been regarded as a relative or absolute contraindication to liver transplantation in many transplant units. Recent data document a success rate for transplantation in alcoholic patients that equals that in other patient groups. Issues relating to the ethical and scientific arguments surrounding this complex area of treatment are discussed. It is concluded that individual patients should be assessed in their own right for this treatment option. It is argued that patient groups should not be denied access to specific life-saving treatments. [Batey RG. The case for liver transplan- tation in end-stage alcoholic liver disease Drug Alcohol Rev 1996;15:183-188]

Key words: alcohol dependence; alcoholism; alcoholic cirrhosis; liver failure; liver transplantation; denial of treatment; survival statistics.

Introduction

Liver transplantation has become a routine treat- ment for end-stage liver disease [1-3]. New surgical techniques now ensure that the operation can be undertaken in children and in adults with complica- tions that previously would have denied them access to the procedure [4]. Superficial examination of liver transplantation costs has led many to conclude that this is an expensive treatment option. In Australia, costs for the procedure and the first year o f immuno- suppressive therapy is in the order of $120 000. Drug costs in subsequent years are estimated at $10 000 to $20 000. These figures should not be taken in isolation from the reality that if patients are not transplanted, the), will require treatment for

end-stage liver disease. Studies comparing the cost of transplantation or of not transplanting a patient with end-stage disease show that transplantation is not dramatically more expensive than the more con- servative approach [5]. From the outset of transplan- tation for liver disease, a number of disorders have been regarded as relative or absolute contraindica- tions to the procedure [4,6]. While there has been a significant shift in thinking about the suitability of patients for transplantation over the past 5 years, there are still some units that would impose very strict limitations on patients with alcoholic liver disease presenting for transplantation. These restric- tions raise questions relating to the scientific and

Robert G. Batey, MD, B Sc (Med), FRACP, Clinical Associate Professor of Medicine, Director of Gastroenterology Department, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle 2310, Australia. Correspondence to Dr Batey.

0959-5236/96/020183-06 © Australian ProfEssional Society on Alcohol and other Drugs

184 R. G. Batey

ethical justification for restricting access to this pro- cedure or any other life-saving therapy. In this paper I argue that liver transplantation should be regarded as an appropriate treatment option for end-stage alcoholic liver disease. Patients should be evaluated individually and a decision not to transplant should be made on the basis of that assessment rather than on a general policy aimed at preventing all alcoholic patients from being transplanted.

The issue of transplanting alcoholic liver disease

Alcohol-related liver disease is the most common form of severe liver disease in many nations and Australia is no exception [4,6-9]. Although alcohol consumption in Australia has plateaued and even fallen in the past decade [9], alcoholic liver disease will continue to be a major problem for a consider- able period to come. Many patients with alcoholic hepatitis will progress to cirrhosis even though their intake of alcohol may have fallen. These patients with advanced liver disease will present to the health system for treatment and adequate responses need to be defined. As liver transplantation is now an ac- cepted treatment for advanced liver disease, the number of transplants carried out each year increases as more units are established in various parts of the world. I f transplantation is accepted as reasonable for patients with alcoholic cirrhosis, it can be pre- dicted that the demand on transplant units will increase significantly with predictable increases in cost to the health system. Data from a number of liver transplant units have documented a change in referral patterns in the past decade [4,10]. In the first decade of liver transplantation, the diseases most co~nmonly transplanted were biliary atresia in children and primary" biliary cin'hosis and primary sclerosing cholangitis in adults. These indications have now been replaced by hepatitis B, hepatitis C and alcoholic liver disease. Sorrell et al. [11,12] report that alcoholic cirrhosis now accounts for 15% of all liver transplantations in major American trans- plantation units.

The decision in the first decade of liver transplan- tation to transplant patients with diseases of un- known aetiology but with a predictable course was based on a number of important facts.

(1) Firstly, these diseases did have a relatively predictable course and patients were other-

wise well, not suffering from multi-system disorders.

(2) Resources were limited and it was fek appro- priate to treat conditions with a more predict- able outcome than conditions that might respond well to medical therapies or to absti- nence from alcohol.

(3) Understanding of the role of transplant in certain diseases was quite deficient.

In the first decade of liver transplantation, alcoholic liver disease was regarded by almost all units as a relative or absolute contraindication to surgery [6- 8,11,13].

As the success of transplantation has become evident, pressure to offer this treatment to all groups of patients with advanced liver disease has increased and changes in the recognized indications for trans- plantation have been made. Some still argue that the changes have been premature and even unreason- able. Fortunately, there are now useful data to guide further debate. Van Thiel and co-workers [13] have identified a number of reasons that were used to justify withholding this treatment option from pa- tients with advanced alcoholic liver disease. These arguments are summarized below.

(1) Alcoholism is not a disease but a behavioural problem or, worse still, a vice leading to self-abuse and thus not deserving of or appro- priate for complex medical interventions.

(2) The high reddivism rate in alcoholics in al- cohol treatment programmes makes the use of expensive technologies inappropriate in the ongoing management of their medical prob- lems.

(3) Liver transplantation outcome figures in al- coholic patients would be expected to be worse than those for other diseases because of the other organ system complications that might be expected in an alcoholic population. Transplantation is an inappropriate use of resources in this group.

Are these arguments valid? Were they ever valid?

(1) Alcoholism is regarded by many as a disease [14-16] and until more is understood about the true pathogenesis of alcoholism, it is inap- propriate to use our lack of understanding as an excuse for denying an effective treatment

The case for liver transplantation 185

to a group of patients. The argument based on the understanding of alcoholism as a pro- cess of self abuse is weakened considerably by our professional and societal Mllingness to be inconsistent in our response to such be- haviours. Treatment is not withheld from the smoking population nor from the diabetic population who fail t o manage their diabetes appropriately. Coronary" artery bypass grafting is not denied to the individuals who have patently over-indulged in the finer "things of life" over many years. To withhold liver trans- plantation because an indMdual has damaged their liver from excessive alcohol intake is not rational if we do offer bypass grafting to patients who are obese and hyperliperdaemic from excessive fat ingestion.

Any reason for withholding transplantation must be based on a more solid set of data than can be provided by the proponents of the first view.

(2) The high recidMsm rate in alcoholics under- taking treatment programmes for alcohol de- pendence is well known [16]. It may appear quite rational, therefore, to argue that it is cost-ineffective to place a hea l@ liver into an alcoholic cirrhotic who has a much greater than even chance of drinking heavily and dam- aging the new liver. Interestingly, this ap- proach has not been taken in patients with hepatitis B and C in whom a high reinfection rate can be expected after liver transplantation. In hepatitis B, 40-60% of patients will experi- ence reinfection of the graft [17] whereas in hepatitis C patients the rate approaches 100% [18]. Two facts need to be stressed here: (a) Data from units that have transplanted

alcoholic patients show that recidMsm rates are low in those selected by an ap- propriately skilled panel. Significant series reported from America and the United Kingdom indicate that a recidivism rate of approximately 20% might be expected over a 12-month period in this group of patients [19-24].

(b) The development of liver disease post- transplant in those patients that do re- commence on regular alcohol is not necessarily predictable as the genetically different allograft may well be less suscep- tible to alcohol-related injury.

(3)

There are no reports in the literature of patients requiring a second transplant for alcoholic liver disease in the allograft although the occurrence of cirrhosis in a transplanted liver has been reported [25].

Data are now available to refute the third argument [24,26-28]. Selected patients--and all patients considered for transplant are assessed and selected for the procedure-- have survival rates that are equal to those in patients transplanted for other conditions. Indeed, alcoholic patients do better than those transplanted for liver cell carcinoma, chola@ocarcinoma or even hepatitis B.

There appear to be few factual reasons for withholding transplantation in patients with alcoholic liver disease. However, it is not a matter of simply arguing that if something can be done then automatically it should be done. If the data support a role for liver transplantation, and I believe they do, the next question has to be:

Should all patients with alcoholic liver disease be con- sidered appropriate for this procedure?

The answer to this question is a resounding no. As indicated already, many patients with advanced liver disease of all types are rejected following a rigorous assessment. No hepatologist would argue that all patients with established alcoholic liver disease should be considered actual liver transplant recipi- ents. All should be adequately assessed by an expert transplantation team.

If these guidelines are adopted, some will still wartt to exclude patients who are continuing to drink at the time of assessment for this therapeutic option. I t is argued that patients should demonstrate a commitment to their own health before transplan- tation is offered. Many have argued over the past decade that patients should be abstinent for 12 months prior to liver transplant and more recently, units have reduced this period to 6 months of abstinence before the operation in carried out. Very recently some units have indicated that they would transplant patients who had been drinking as re- cently as 1 week prior to surgery. Data have chal- lenged the profession. Some patients who have consumed alcohol up until the time of transplan- tation have achieved excellent survival results and have given up alcohol post-operatively [23]. I would

186 R. G. Batey

argue that in 1996 patients should not be excluded automatically from consideration of liver transplan- tation if they are still drinking at the time of their assessment. The procedure should be delayed and the effect of a period of abstinence on liver function assessed before any decision to operate is made. In the case of acute liver failure in an alcohol-depen- dent individual the case is different again. There is no time to assess the effect of abstinence and in a young patient transplant may be the only viable option. Recent alcohol intake should not exclude transplant as an option.

It must be stressed that liver transplantation is not a cure for alcoholism or alcohol dependence. Equally, it must be stressed that abstinence can lead to marked improvement in liver function thus avoid- ing a need for surgery [4].

What then is a praclical solution to this vexed issue?

Given the fact that alcoholic fiver disease is a common condition for which no very successful medical treatment exists, we do have to consider radical options when younger patients present with signs of hepatic decompensation. While the litera- ture abounds in articles extolling the virtues of a number of drugs in controlling the alcoholic liver disease itself, rather than the complications of chronic fiver disease of any sort, these papers do not provide much joy to the clinician seeking to treat patients with severe liver disease. Unlike the author of a paper in the British Journal of Addiction [29], I do not believe that steroids have a major role in the treatment of alcoholic hepatitis or cir- rhosis. Despite repeated studies, evidence at the moment shows that steroids only have a role in the most severely ill alcoholic hepatitis patients, a group with a mortality rate of 30-35% in many series [30]. Propylthiouracil has been shown by Orrego and colleagues [31] to have some benefit in the management of acute alcoholic hepatitis and in patients with alcoholic hepatitis followed-up over 2 years [32] but no other studies have confirmed their data. The use of this drug is not widespread because clinicians remain unconvinced of its value at this stage. While it is possible to treat the complications of chronic alcoholic liver disease, as it is to treat the complications of any other form of chronic fiver disease, sooner or later the liver decompensates and the outcome of this is either

death or acceptance onto a liver transplantation programme. It may be argued that the cost of transplantation is high and that it should be re- served for a selected group in the community. However, the cost of not transplanting patients with advanced alcoholic liver disease will also be high as these patients will present to hospital emergency departments with the consequences of cirrhosis, portal h)qaertension and evoMng liver failure. Treatment of these medical problems will require hospitalization with the attendant costs.

In transplanted patients an ongoing drag cost will be generated by the need for anti-rejection agents but these costs must be counterbalanced by the fact that a significant proportion of transplant recipients return to the active work-force and enjoy a much more productive life than they were used to prior to transplantation. Currently, we have no accurate cost-benefit analyses comparing the options de- tailed.

I argue that liver transplantation should be con- sidered for all patients who have advanced alcoholic liver disease, who are under 65 years of age and who are willing to consider giving up alcohol, acknowl- edging that continued use of this drug will lead to adverse consequences. In patients who emphatically refuse to stop drinking, transplantation should be withheld. This decision is based on the reality- that if patients are not willing to assess the benefit of abstinence on their current liver problem, they may not adhere to an abstinence programme post-trans- plantation. This decision is different from one based on a policy that excludes all drinkers automatically from liver transplantation. All patients with al- coholic liver disease considered for transplant should be assessed fully by the liver transplant unit to which they are referred and in addition to the usual assess- ment process, tests should be undertaken to deter- mine whether there are any cognitive deficits consequent on heavy alcohol use in the past. A determination of the degree of dependence of these patients must also be made as this information may influence the decision to transplant. Patients with alcoholism should also be examined for evidence of injury" to other organ systems including the cardio- vascular system and the endocrine system. Van Thiel and colleagues [13] have identified that some of the hormonal changes in chronic alcoholics can be re- versed by liver transplant but patients who have significant alcoholic cardiomyopathy may not survive

the operative procedure. Having defined all of these issues, if an alcohol-dependent person is deemed appropriate for transplant, they should be transplanted in the knowledge that they wilt do as well as any other patient put up for liver transplan- tation.

W/mt o f t/Je Australian experience?

Australian transplant units took a conservative line with respect to alcoholic liver disease for the first 4-5 years of their experience. Subsequently, an in- creasing number of patients with alcoholic liver disease have been referred for assessment. Recent figures from the three oldest transplant units in Australia indicate that over a period of 7 years, of 119 alcohol using patients referred for transplant assessment 35 were transplanted and eight have had the decision deferred pending reassessment. Of the 35 transplanted patients, outcome figures have been the same as those for other groups of patients transplanted at the same time.

There would appear to be no good reason for rejecting patients who have alcoholic liver disease from consideration for liver transplant. Indeed, data from Lucey and colleagues [22] indicate that failure to transplant some of these patients is associated with a significantly worse outcome. It is clear that those who have advanced disease at the rime of assessment would do poorly i f not trans- planted but equally- patients regarded as having well compensated liver disease have done worse than their colleagues transplanted for similarly severe disease.

Currently, there is evidence that in the United Kingdom many patients who could be considered for transplant because of alcoholic liver disease are not being referred for consideration [33]. The same situation almost certainly applies in Australia and perhaps to a lesser degree in the United States. Many still regard transplantation as a very expensive experimental treatment option. Reality dictates that liver transplantation should be considered as a rou- tine treatment option for patients with liver disease of any aetiology.

It is to be hoped that ongoing debate will stimu- late further interest and expand discussion of this important therapeutic dilemma. I conclude with nay opening statement, that I believe that all patients with end-stage alcohol-related liver disease should be actively considered for liver transplantation.

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The case f o r l iver transplantation 187

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