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

BARCELONA . SPAIN
138 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 139
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
Chronic alcohol consumption can lead to progressive cardiac dysfunction, resulting in congestive
cardiomyopathy. Alcoholic cardiomyopathy is characterized by an increase in myocardial mass, dilation
of the ventricles, and wall thinning. Changes in ventricular function may depend on the stage, in that
asymptomatic stage is associated with diastolic dysfunction, whereas systolic dysfunction is a common finding
in symptomatic patients, leading to heart failure in latter stages. Moreover, cirrhosis per se is associated
with impaired cardiac contractility. This phenomenon of attenuated cardiac responsiveness to stimuli is
termed cirrhotic cardiomyopathy. The emergence of LT as an effective treatment for alcoholic cirrhosis has
led to the recognition of previously subclinical cardiomyopathy and congestive heart failure accounts for
significant mortality and morbidity after this procedure. Coronary heart disease which is associated with
excessive alcohol consumption needs to be extensively examined in the setting of transplantation.
Numerous clinical and experimental studies have demonstrated that excessive alcohol consumption
has deleterious effects on the kidney. A variety of tubular defects have been described in these patients,
often reversible with abstinence. On the other hand, IgA nephropathy has been demonstrated in chronic
alcoholism, with irreversible lesions responsible for asymptomatic proteinuria. This raises the possibility
that alcoholic cirrhosis itself and the attendant abnormalities in renal function may predispose the liver
transplant patient to permanent renal damage when treated with calcineurin inhibitors.
The progression of alcoholic liver disease to decompensated cirrhosis stage has profound effects on
hepatic metabolism and ultimately, on body composition and weight. This results in profound nutritional
changes that include weight loss and evidence for protein caloric malnutrition. Moreover, malnutrition is an
additional developmental factor in the functional and structural muscle damage induced by chronic ethanol
consumption. The impact of nutritional status on outcomes after LT has been studied. Poor pre-operative
nutritional status was associated with longer intensive care unit stays and increased likelihood of posttransplant
infections.
There is a clear association of heavy alcohol consumption with cancers of mouth, larynx, pharynx, and
oesophagus. Moreover, alcoholics are also often heavy smokers. It is crucial to rule out any neoplastic
disease or pre-neoplastics conditions during the pre-transplant evaluation, since ALD patients appear to
have a higher incidence of malignancies after LT, especially oropharyngeal carcinomas.
The first approach to ensuring abstinence after transplantation has been to try to select during the pretransplant
period only those patients likely to maintain abstinence. A recent meta-analysis identified 3 pretransplant
factors associated with alcoholic relapse after LT: lack of social support, a family history of
alcoholism, and less than 6 months of abstinence from alcohol (8). There is a lack of consensus for the
duration of abstinence from alcohol, as well as what constitute good psychosocial criteria for listing for LT.
Abstinence is essential and the pre-transplantation period should be used for strengthening the motivation
to end alcohol use. This discontinuation commits the patient to a therapeutic program which may prevent
post-transplantation relapse. However, the so-called 6-month rule (a duration of 6 months of abstinence
before LT) has not demonstrated its ability to predict relapse after LT, and should no longer be the definite
rule and should not be the determining factor for graft access. A 3- or 6-month period of abstinence before
transplantation may be justified when carried out as part of a larger strategy for management of alcohol
dependence. It should take into account time for motivation, achievement of abstinence, and for the
prevention of relapse, and should never be carried out under the pretext of coercion. Moreover, alcohol
withdrawal is sometimes associated with recovery of liver function : three months of abstinence may unmask
those with truly irreversible ALD (9). Patients with a lack of social support, personality disorders, or a pattern
of non-adherence should be listed only with reservation.
LT for ALD should be a central event in the management of the alcoholic patient, imposing some
responsabilities on the medical team in its follow-up care. The participation of a team specialized in
addiction problems in this period should be recommended and their involvement should be based on a
contract of care. Without being a written document, this contract may be seen as a therapeutic alliance in
which empathy plays a key role.
In summary, it is possible to place patients with ALD on the waiting list under two conditions:
• that there is a pre-transplantation assessment with particular attention paid to the presence of: lesions
related to alcohol consumption or smoking; extra-hepatic lesions, such as cancers and precancerous
conditions including oropharyngeal, bronchial, esophageal; respiratory and cardiovascular pathology.
• that alcoholic care management is started as early as possible by a team specialized in addictive behaviors.
Many studies suggest that short- and mid-term results of LT for ALD are not influenced by alcohol relapse.
However, beyond five years, it seems that long-term survival is reduced because of other target-organ
damage of both alcohol and tobacco, especially aero-digestive malignancies, which are greater causes of
morbidity and mortality than is recurrent ALD.
Finally, we have to keep in mind the dichotomy between ethical issues and public perceptions, that is well
illustrated in the debate about LT for patients with ALD : does the general public support organ donation for
patients with ALD Societal attitudes towards these patients must change. The alcoholic patient, candidate
for LT, should be considered as suffering from a double pathology, both hepatic and alcoholic.
REFERENCES
Burra P, Senzolo M, Adam R, et al. Liver transplantation for alcoholic liver disease in
Europe: a study from the ELTR. Am J Transplant 2010;10:138-148
Julapalli VR, Kramer JR, El-Serag HB, et al. Evaluation for liver transplantation: adherence
to AASLD referral guidelines in a large Veterans Affairs center. Liver Transpl 2005;11:1370-1378
Kotlyar DS, Burke A, Campbell MS, et al. A critical review of candidacy for orthotopic
liver transplantation in alcoholic liver disease. Am J Gastroenterol 2008;103:734-743
Lucey MR. Liver transplantation in patients with alcoholic liver disease. Liver Transpl 2011;
17:751-759
Vanlemmens C, Di Martino V, Milan C, et al. Immediate listing for liver transplantation
versus standard care for Child-Pugh stage B alcoholic cirrhosis: a randomized trial.
Ann Intern Med 2009;150:153-161
Lucey MR, Schaubel DE, Guidinger MK, and al. Effects of alcoholic liver disease
and hepatitis C infection on waiting list and posttransplant mortality and transplant survival
benefit. Hepatology 2009;50:400-406
Mathurin P, Moreno C, Samuel D, et al. Early liver transplantation for severe alcoholic hepatitis.
N Engl J Med 2011; 365:1790-1800
Dew MA, DiMartini AF, Steel J, et al. Meta-analysis of risk for relapse to substance
use after transplantation of the liver or other solid organs. Liver Transpl 2008;14:159-172
Veldt BJ, Lainé F, Guillygomarc’h A, et al. Indication of liver transplantation in severe alcoholic
liver cirrhosis: quantitative evaluation and optimal timing. J Hepatol 2002;36:93-98
Weinrieb RM, Van Horn DHA, Lynch KG, et al. A randomized, controlled study of treatment
for alcohol dependence in patients awaiting liver transplantation. Liver Transpl 2011;17:539-547
The second approach to reducing the risk of post-transplantation drinking is to initiate alcoholism therapy
before transplantation. Results are disappointing (10). It appears that alcohol-dependent liver transplant
candidates struggle with total abstinence before transplantation. Treatment interventions to effect robust
and lasting sobriety in this population are limited. It is also important to emphasize that the severity of liver
disease in these patients is so substantial, that a rigorous approach is quite difficult.