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

BARCELONA . SPAIN
136 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 137
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
LONG-TERM MANAGEMENT OF ALCOHOLIC LIVER DISEASE
EVALUATION AND SELECTION OF CANDIDATES FOR LIVER
TRANSPLANTATION
Georges-Philippe Pageaux
Montpellier, France
E-mail: gp-pageaux@chu-montpellier.fr
KEY POINTS
• Alcoholic cirrhosis, with or without hepatocellular carcinoma, is the second cause of liver
transplantation (LT) in Europe and United States.
• When we take into account the usual criteria for success in LT (patient and graft survival, rejection
and infection rates), alcoholic liver disease (ALD) is a good indication for transplantation, with
1- and 5-year survival rates of 84% and 73%, respectively.
• Some disparities are observed at the referral level when patients with ALD are compared with
non ALD patients.
• Recent results support the current procedure of giving priority for organ allocation to the
sickest patients.
• The pre-transplant investigation is based on assessing the patient’s conditions and alcoholrelated
co-morbidities that might limit the potential for successful transplantation.
• 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.
• 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.
• The alcoholic patient, candidate for LT, should be considered as suffering from a double
pathology, both hepatic and alcoholic.
The French Committee of Health Education estimates that the number of people having excessive alcohol
consumption in France is about 10% of the general population. It is estimated that the number of registered
deaths per year in France, which are related to excessive and regular alcohol consumption is 45,000.
There are 8,000 to 10,000 annual registered deaths linked to a complication of alcoholic cirrhosis. Alcoholic
liver disease (ALD) is the most common cause of cirrhosis in western countries. Consequently, alcoholic
cirrhosis, with or without hepatocellular carcinoma, is the main cause of liver transplantation (LT) in France
and the second in Europe and United States.
The controversy surrounding ALD as indication for LT has already stirred debate regarding the duration of
abstinence before transplantation and the risk of recurrence, resulting in several recommendations for LT
indications. Guidelines evolve according to prevailing opinions, but there is a consensus that, to the extent
that there is a multidisciplinary approach to the patient, ALD is as good indication for LT as are other chronic
liver diseases.
When LT is considered in a patient with ALD, several points need to be emphasized: the under-referral
of these patients to liver transplant programs, choosing the optima timing for transplantation, the pretransplant
abstinence, the pre-transplant evaluation.
In patients with end-stage ALD, the 5-year survival without LT is < 25%, when it is > 70% if LT is performed.
Thus, ALD has become one of the main indications for LT. It emerges from most studies that when we take
into account the usual criteria for success in LT (patient and graft survival, rejection and infection rates),
ALD is a good indication for LT. According to the European liver transplant registry, survival after TL for ALD
is 84%, 73%, and 58% at 1, 5, and 10 years, respectively, significantly higher than in viral and cryptogenic
cirrhosis (1). However, the main issue is the likelihood of relapse and its influence on the outcome, because
it is the possibility of returning to alcohol use that separates patients with ALD from those with other forms of
chronic liver disease. Consequently, some disparities are observed at the referral level when patients with
ALD are compared with non ALD patients (2). Thus, less than 10% of the 70-100,000 patients per year who
develop decompensated cirrhosis due to ALD in United States are referred for transplant (3). The attitude
of physicians to alcohol addiction is likely an influence on the referral of ALD patients for LT. Some of them
hold pejorative views of patients who suffer from alcohol abuse and dependence. Others are confused
about when they should refer their patients for an LT evaluation and about whether a specific interval of
abstinence is needed before any referral (4)
Concerning the timing of LT in ALD patients, recent results support the current procedure of giving priority
for organ allocation to the sickest patients. A recent randomized trial has demonstrated that immediate
listing for LT did not show a survival benefit compared with standard care for Child-Pugh stage B alcoholic
cirrhosis (5). In addition, immediate listing for transplantation increased the risk for extra-hepatic cancer.
In contrast, a retrospective analysis of the UNOS database showed that ALD patients with relatively low
MELD scores in the range of 9 to 11 derived a survival benefit (6). Patients with severe acute alcoholic
hepatitis present particular challenges to transplant teams because they have obviously consumed alcohol
in the previous month. A recent French, multicenter, case-control analysis about patients presenting their
first episode of severe, cortico-resistant acute alcoholic hepatitis demonstrated that they had an excellent
intermediate-term survival and a low frequency of harmful drinking after LT (7).
In addition to evaluating the severity of the liver disease, the pre-transplant investigation is based on assessing
the patient’s conditions and co-morbidities that might limit the potential for successful transplantation.
Among the numerous extra-hepatic complications of alcoholism, we have to focus on the followings during
the pre-transplant evaluation : pancreatitis, neurological manifestations, heart disease, renal disease, poor
nutritional status, and cancers.
Several studies have demonstrated a close relationship between alcohol consumption and acute/chronic
pancreatitis. In the setting of transplantation, one must consider the probability of the sequels of previous
manifestations of the disease such as abcess, venous thrombosis, adherences, which could make more
difficult the surgical transplant procedure. Moreover, carcinoma of the pancreas may occur with increased
frequency in alcoholic patients, although it correlates better with cigarette smoking than with alcohol
consumption. The exclusion of pancreatic carcinoma in a patient with chronic alcoholic pancreatitis may
be a difficult diagnostic problem. Thus, high quality imaging tests are necessary for the pre-transplant
evaluation.
Wernicke’s encephalopathy and Korsakoff’s syndrome are nutritional disorders caused by thiamine
deficiency. Chronic alcohol consumption can result in thiamine deficiency by causing inadequate nutritional
thiamine intake, decreased absorption of thiamine from the gastroeintestinal tract, and impaired thiamine
utilization in the cells. Mental confusion in the main characteristic of these diseases, sometimes difficult to
distinguish from hepatic encepalopathy. Treatment consists of parenteral thiamine, but in the majority of
patients with Korsakoff’s syndrome, recovery is incomplete. This situation represents a contraindication for
LT.
Alcoholism is also responsible for dose-related injury to the peripheral nervous system. Direct cumulative
neurotoxicity from alcohol, nutritional and vitamin deficiencies associated with alcoholism, and liver cirrhosis
itself each probably contribute to this peripheral neuropathy. Resolution of alcoholic neuropathy following LT
has been reported. Thus, this manifestation does not request a contraindication to transplant. However, it
must be emphasized that calcineurin inhibitors immunosuppressive agents used after transplantation have
some degree of dose-related peripheral neurotoxicity which can worsen a pre-transplant neuropathy with
some degree of disablement.