Liver transplants for alcoholic liver disease

RJ FINGEROTE, VG BAIN, RN FEDORAK. Liver transplants for alcoholic liver disease. Can J Gastroenterol 1991;5(6): 195198. Alcohol related enJ-srage liver d.~ase is a pri ncipal cause of liver failure. The scarcity of donor livers and the predominance of alcohol related end-stage liver disease has raisc<l the issue of mclu<ling alcoholic.~ as can<lidaces for liver transplantation. In rationalizing the arguments for and aga inst the treatment of alcoholic end-stage liver Jbease with transplan tat ion, factors such as recidivism, resource allocation and principles of medical practice must be consi<lereJ. Public confidence in organ tr,msplantation depends on the scientific validity and moral integrity of the J'<llicies adopted. Sound pol icies will prove defensible while policies based on percept ions or prejudices will, in the long run, harm the process.

D lJRIN<.~ 1111' PAST IWCADE, I IVFR rrnn,plantat 1 011 has progressed fro m an experrmcnrnl procedu re to a rccogn ized t hcrnpcut ic llptinn for parients with progres!o.lVl' irreversible liver disease.Transplantation md1cations have expanded to such an exten t rhat, al presen t , it 1s considered t he t reatment of choice fnr LhrontL endstage live r failure secondary Lo hep:ttocell ula r liver disease, Lholestatic liver disease, selected hepatic malignanues, and inherited metabolic disorders.In aJJitton, trnnsplantatton has hecnme the treatment of choice for irreversible fulm111nnt and suhfulminnnt hepat ic failure ( I ).Nevertheless, controversy cont111ues to surround the questtnn of the use of li ver rrnnsphtntatio n for the single most common cause of ch ron ic liver disease 111 North America -alcoho l abuse.Recen t reviews have presented argument, hoth for and aga inst li\'er tmrn,plantatton in alcoholics (2, , ).
It ts estt mmed that Hpproxnnately I 0% of the adult population 111 the U ni ted States consume., exccssi,•e amounts of alcohol, which results in over I 00,000 deaths a nnuall y, I 9% of wh1d1 ,ire att ri huteJ to chron ic liver failure.The coM of rreating the prohlcm of alcohol ahuse amounb to over $1 16 hillilln per year, which repre,ents approximately I 2% of annual health care expenditures.It has heen sugge,ted that alcoholics should not he Gindidaces fo r liver tramplancation for alcllhnl-rclatcd c irrhosis.Arguments which support this viewpoint focu, on issues ,uch as recidivism, disease se lf-inflicrton and resource allocarion.

RECIDIVISM
Concerns regarding the 1 ikelihood of rcc1div1sm among patients with alcoholism after Lhcy have received a liver transplant have heen a maior deterrent to providing these pc1ticnts with transplants (1 ).In 1988, Starzl ,md colleagues ( 4) reported a one year survival rate of 7 3'Yo for patients with alcohol related end-stage liwr dbcase, comparahlc to that of patients transplanted with other causes of end-stage liver disease.Recently, Kumar ct al ( 5) reported that, of 73 patients who received liver transplants for alcoholic liver disease, onl) s ix of the 52 surviving recipients rest11ncd alcoho l consumption, all of who m reported consuming three or fewer drtnb per wee k.One patient had died of a llograft rcjectton after discharge from hospital ; this patient's death was in part a result of recurrent alcohol abuse (5).ln a \econd sru<ly from the University of Michigan, 32 alcoholics underwent liver transplantation for end-stage liver disease.After a mec1n follow-up of five months, one pauent wm, noted co have used alcohol on one occasion only (6).I lowever, since the follow-up time of these studies was short, the potential of recidiv ism rema ins a m .1jorc,mcern.
In a later study from the same unit reporting on 45 patients undergoing transplantation for alcohol related endstage liver disease, five pc1c1ents returned to alcohol use.Survival data J1J not differ from re~ults for liver transplant in nonalcoho lic patients.Follow-up was greater rhan l 2 months in 28 patients (7).Psyc hological wellbeing of alcoholic liver transplant patients following transplc1ntation has been examined and is s imilar tn that of nonalcoholic recipients (8). 196 Neither of the~e srndics u:.ed preopernuve sobriety as a selection criterion.In thb regard, Scad ct al (4) suggested that "the 1mposit1on of ;rn arbitrary period of absunence hefore transplantation would seem medically umound o r even inhumane.''Reports from other trnnsplam centres arc necessary before the importance of a period of abstinence can he determined.
Certainly, returning to heavy drinkmg could rum a transplanted liver over a number of years.More likely, relapse inll> heavy drmkmg would interfere with the daily ingestion of multiple medications essential for 1mmunosuppression and survival.As well, alcohol may interfere with both the absorption and mcrnholism of medication:.necessary post tramplantat1on.Alcohol is an inducer of the P-450 system and as cyclospon ne 1s metabol ize<l hy the P-450 system alteration in immunosuppression may result.As a group, therefore, the patients with alcoholic cirrhosis may have a lower survival rate after rece iving a transplant than Jo controls.Nevertheless, these possibilities do not provide solid reasons for excluding those with alcohol related end-stage liver disease from considerntion for transplantation.

GENETICS OR LIFESTYLE?
A second argument that has been advanced against liver transplantation for those who are alcoholics is that, since liver fai lure secondary to alcohol ahuse is a self-mflic teJ disease, society should not assume the burden o f care for alcoholics with liver fai lure.Support for this po int of view is tenuous because there is little doubt that alcohol abuse has a genetic component.
A 1,pecific gene has been ide ntifi ed in the brain tissue recovered during post mortem examinations in 69% of a series of '35 known c1lcoholics, com-parcJ with 20% of,\ series of 35 mmalcoholics from the general population (9).There is also a higher concordance of alcohol abuse in mon nzygot ic twins compared to that in fraternal twins ( 10).S tudies have Jemon~trated chm, even when raised apart from their alcoholic parents, sons of alcoholics have a higher rate of alcohol abuse ( I I).Alcohol abuse may he found in people suffering fro m depress ion or personality disorders, hoth of which have strnng genct ic predispositiom.Thus, it is deharnhle whether alcohol abuse is a Ii fest yle decision or the result of a genetic predispos1t ion.
Even if alcoholism was a 'li fes tyle disease', would that truly remove from society the burden of providing optimal medical cm-c to patients With alcohol related liver failure?Soc iety accepts the burden of rreaLing diabetes mcllitlls in obese patients whose diabetes might be controlled by dietary restrict ion alone.Similarly, cigarette smokers arc not denied the privilege of admission to an intensive care unit, or of a hcc1rt transplant should they develop ischem1c car<liomyopathy, or of surgery should they develop lung cancer.Arguahly, horh overeatmg and c igarette smoking are dec isions of lifesty le in much the same way as ::ilcohol ahusc.Denial of hcalt h care benefits m the ohcsc pattent and the cigarette smoker is nor a social practice; thus, it would seem anomalous to deny full health care benefits to those who suffer from c1lcohol 1~m.

RESOURCE ALLOCATION
Liver transplantation uses a nonrenewable and extremely scc1rce resource -a donor liver.A lthough patients with alcohol related end-stage li ver disease represent approximately 50% of patients with end-srnge li ver disease, patients with alcohol related liver disease currently account for less than l 0% of those rece iving transplants (2).
In the fut ure, as large liver transplant programmes deplete the pool of patients with nonalcohol related causes of liver failure who require transplantation, they may trnnsplant more patient:.with alcohol related liver failure in order to maintain the therapeutic momentum of the programs.Obviously, if patients with alcohol related end-stage liver disease were accepted for liver transplantation on an equal basis with patie nts whose disease is nor related m alcohol ism, an enormous number of additional candidates might further exacerhmc the problems stemming from scarcity of do nor li ver~.A ltho ugh t he allocation of orga ns in sh ort supply Joes presen t vex ing ethirnl problems, this fact cannot he allo wed to become Lhe basis for a mora listic pu blic po licy which advocates se lecti ve punishment of a certa in group o f pa tie nts whose disease may, in fac t, be gen e tica lly Lriggered.

PRINCIPLES OF PRACTICE
Neverth eless, in the face of limi ted health care resources, it is c ritica l to establish princi ples ro guide allocatio n of transpla nt o rgan~.Dosse to r (1 2 ), established th ree dime nsio ns unde r which ethical issues rela ting to th e allocation of rndnveri c nrgans could be discussed: m ic ro-alloca tion , mac ro-allocation and mega-alloca tio n.
At the mic ro-allocation le ve l, issues as they e xist be twee n the patie n t and his or her phys ician arc addressed.In the case of liver tra nsplantat io n, suc h issues include decis io ns a bou t whe the r rhe patien t wish e~ tn undergo li ver transplanta tio n a nd wheth er th e physician fee ls t he procedure is a ppropriate fo r rhe pa ti ent, from bot h a phu-•iological and psych o logical point of view.Extrahepa t ic dysfunc tio ns associated with a lcoho l related li ver disease, such as cardi om yopat h y o r chronic o rga n ic brain syndrome may contraindicate li ve r tran spla n tation.
At the macro-allocation level, issues relate to stat istics, programs or economics.A transpla n tation program committee migh t cons ide r a pat ie nt with alcoho l re la reJ live r d isease a n inappropria te t ranspla n t canJ idate due ro a lack of economic resources, concern regard ing a poor result o f surge ry, or limitation s o n the tota l numbe r of transplants to be done .
At the mega-allocat ion level, issues addressed a re o f a more po liti cal natu re; these decisions are n ot linked solely to the cause of th e pa t ie n t's li ve r di sease.Vigorous oppositio n to liver transpla ntation might come fro m a "puri tan ic element who wou ld n ot want to see public resources used fo r a procedure on mJ ividuals not soc iall y approved ofwho, in fac t, have brough t on their troubles by the ir own s inful ac t ions" ( 14), or a government m igh t d ecid e to d iscontinue comple rcly fun d ing o f rra n:,planta t io ns in th e face of risi ng h ealth cn:,ts.
T rad itiona lly, need has been Lhe gu id ing c rite ria in dete rmining whn sho uld unde rgo liver 1 rnnsplanration .This may be a ppropria Lc wh e n e no ugh resou rces cx isr that eve ryon e who requires these resources may receive the m; h owever, in con side ring the I imitecl numbe r of transpl an table li vers ,i vailable, o the r allocative m ec hanisms rn:ed to be con sidered ( 12).These include a lll>catio n of the basb of: the hest m edical outcom e; rando m selec tio n haseJ on ch an ce; first come, first served; a bility to pay; socia l wonh; the 'squea ky wheel' facto r in w hic h fa mi ly or public pressu re is used to influe n ce medical decis io ns; medical-legal consid erat io ns; a nd public po licy.Most of these .1 llocarion facto rs do n ot concentra te on the physician's or th e patie n t's va lu es.For in sta n ce, program a nd institutiorrnl va lues arc most strong ly represented in J ecis io ns based upon medicopolitical consideratio n s.
Social worth a nd th e ability to pay as a llocation principles C()mple tely ign o re suc h fac tors as causa li ry and med ical ind ications fo r procedures.A lth ough ph ysica l need clearl y h as to be established in nrd e r to make an invas ive proced ure suc h as liver transpla nta tio n medically a ppropria te, th e indicatio ns for surge ry may also he dependent upo n the n o nmedical fac tors previously o url inecl.Whe n used in the past as c rite ria for th e allocation of health care resources, socia l wo n h h as led LO a s ituat ion in whic h resources we re a llocated to chose me mbe rs nf socie ty who most closely resemble m e mbe rs of the a llorntin comm ittee.C iti n g social worth as a fac tor in tran spla n t a llocati on , George D Lund berg comme n ted (13 ): "If I had one liver w trans/Jlam a nd 50,000 possible recipients, 1 wou/.d11't let the fact that a great creative genius might drink again deter me from giving him or her a needed new liver 10 allow a11od1er 30 years of creativity."T h us, allocati o n o n the has is of social worth ope n s the door fo r a rbitrary value judgeme n ts a bout such fac tors as inte lligence q uotie nt, nation ality, race Liver transplants a nd relig io n ( 14).W n h the~e allocatio n foc tnrs in mind , on e must a ppraise aga in the issue of li ver 1 ran~pla ntat io n in the ca~e o f patien ts w ith alcoho l rc-1,n ed li ver di~c,be.

CONCLUSIONS
The l lippocrau c Princ iple would suggest ch a r the h calt h care professio na l is obl il{ed Lo t re,n the pati e nt in the manne r whic h would n1tist he ncfiL th e pati en t.C learl y, fo r a p,lt ienr dying fro m alcoholic live r fa ilure, 1 he on e procedure most likely to prnv1de a lasting bencfir i~ I ive r t ranspl an ta tio n .S uccess rnLCs repllrLCd fo r case~ o ( Ii ver transplantatio n in alcoho lic live r disease arc ~imila r to those repori ed for transplantatio n necessit a ted as a result of othe r causes o f ch ronic li ver failu re .The refo re, risk of tra nsp la ntatio n fa ilure is n ot a va lid reason to de n y a liver transplant co a patie nt w ith a lcoh o l related e nJ-5tage liver disease.Refusing a n alcoho lic pa tie nt a l ive r transpla n t because of ,1 con cern regarding rec idivism may reOcct a lack of confidence in th e capahil iry of modem med ic ine to re h a bilitat e thnsc wiLh chronic a lcoho li& m , or it may refl ect a selec ti vel y moral approac h to all ocation procedure:.. Failure to consider alcoholi cs equally for li ver trnnsplan rntion will open the dcx,r to othe r judgements of ind iv idua l worth: Is a prnslin1 L e with fulminant hepa titb B worthy of th is same resource?What abou t a ynung pa tient with W ilson's disease in d ying need p rec ipitaLed by hi~ o r he r own J ecisio n to stop penic illa mine? A:, has been :,ugge~ted by Verhey ( I 5): "When scarcity makes allocation necessary, sanctity requires random selecticm and for bids the God -like jwliemenL chat one life is wonh more than another.Random selection alone will sustain a re/LLtionship of truthfulness and trust beaueen /> irysician and /Jatiem.We may not deny scarciry, we may not deny sanctity; the best we can do is to act with integrity." A po licy adopting Verh ey's a pproach wou ld favour allocation whic h avoided va lue-laden a nd thus da ngerously prejudiced select ion c rite ria.
l n summa ry, in assessing th e role of liver transpla n tat io n in a lcoh o lic liver d isease, the issue of the etio logy of I iver FINCEROTE ct al fa ilure cannot an<l must not be used in dete rmining wheth e r transplantatio n is an appropriate form nf therapy.Patients must be judged exclusively on the has is of their willingness to undergo the procedure and thei r suiLability for the procedure as determ ined by hard sraristical analy~is of darn generated by prope rly conducted rriab.