Liver
transplantation for patients on methadone maintenance
( Liver transplantation
for patients on methadone maintenance: ) New From: Liver Transplantation
September 2002 Volume 8 Number 9 Medline
Abstract at NLM. Kanchana TP, Kaul V, Manzarbeitia C, Reich DJ, Hails
KC, Munoz SJ, Rothstein KD. (from the Division of Gastroenterology, Albert
Einstein Medical Center, Philadelphia, PA. Liver Transpl 2002 Sep;8(9):778-82).
Orthotopic liver transplantation (OLT) is well established as an
effective treatment for patients with end-stage liver disease (ESLD). One of the
major challenges currently facing OLT is that the number of candidates far
exceeds available organs. As of May 2000, a total of 15,258 patients were on
waiting lists. Hepatitis C is the leading cause for OLT, followed by alcoholic
liver disease; both are primarily substance abuse-related diagnoses. Recipient
selection is a critical aspect of OLT and involves a multidisciplinary approach.
Patients undergo an extensive psychosocial evaluation in addition to medical
evaluation. Currently, patients actively using illicit drugs are excluded from
consideration for OLT.3-5 Methadone maintenance treatment (MMT) is routinely
prescribed for patients during and after rehabilitation from heroin use.
Patients on MMT appear to fare better with respect to social functioning, job
rates, lower imprisonment, and human immunodeficiency virus infection compared
with patients denied methadone after rehabilitation from heroin use. Although
patients fully rehabilitated from previous drug use are considered OLT
candidates, there is a paucity of data regarding OLT in patients administered
methadone at the time of OLT as part of MMT.
Only 56% of transplant
programs accept patients on MMT for OLT, and 32% of programs require
discontinuation of MMT before OLT. This apparent discrimination against patients
on MMT has occurred although there are no published reports about the outcome of
OLT in patients on MMT. We describe our experience with patients on MMT who
underwent OLT at our center.
Commentary from Jules Levin: At this year's
NIH HCV Consensus Conference the panel supported not excluding IVDUs from HCV
treatment and recognized the need to consider therapy for IVDUs since IVDU is
the biggest contributer to HCV-infection. The HCV-infection rate in methadone
programs is very high. If we as a society are going to address HCV as a serious
disease, and it was said to be recognized as an epidemic at the NIH Meeting, we
must come to grips with the IVDU population.
Abstract: Most transplant
programs require abstinence of at least 6 months from alcohol and illicit drugs
before orthotopic liver transplantation (OLT). However, there are no published
data regarding OLT outcomes in patients who are currently on methadone
maintenance treatment (MMT) as part of the treatment of their heroin addiction
at the time of OLT. The objective of this study is to evaluate our experience
regarding the outcome of OLT in patients with end-stage liver disease (ESLD) who
were on MMT at the time of OLT. Between March 1993 and May 1999, a total of 185
patients with ESLD underwent OLT at our center. Five transplant recipients
(2.7%) had a history of heroin abuse and had undergone drug and alcohol
rehabilitation, but could not be weaned off methadone. Pre-OLT status, drug
history, perioperative course, compliance with medical therapy, post-OLT
follow-up, and patient and allograft survival were analyzed in detail in these
patients. All patients on MMT underwent uneventful OLTs. Their compliance with
medications and follow-up was excellent. One patient was weaned completely off
methadone after OLT. Post-OLT mean hospital stay in this group was 43 ± 25 days.
Although the number of patients was small, long-term outcome of liver transplant
recipients on MMT appears similar to that of patients not on MMT who underwent
OLT during this period. Our results suggest cirrhotic patients on MMT should be
considered for OLT if they meet the same psychosocial requirements as patients
with alcohol abuse. Furthermore, it is not necessary for patients to be weaned
off methadone before OLT. (Liver Transpl 2002;8:778-782.)
Data from
liver transplant recipients between March 1993 and May 1999 at the Center for
Liver Disease, Albert Einstein Medical Center (Philadelphia, PA) were carefully
reviewed. Of 185 patients who underwent OLT at our center during this period, 5
transplant recipients (2.7%) had a history of heroin abuse and had undergone
drug and alcohol rehabilitation, but could not be weaned off MMT. These patients
underwent a complete pre-OLT evaluation and were abstinent from drug and alcohol
use for at least 6 months before listing for OLT. They also underwent extensive
psychosocial evaluation and were deemed suitable liver transplant candidates
only after psychosocial clearance, which consisted of clearance from a
psychiatrist, social worker, and their rehabilitation center. The 5 patients
described in this report were on MMT at the time of OLT.
In CONCLUSION,
our results show that PATIENTS ON MMT CAN SUCCESSFULLY UNDERGO OLT. These
patients must undergo proper rehabilitation and have a thorough psychosocial
evaluation before they can be considered for OLT. Our results suggest that
weaning completely off methadone therapy should not be an essential requirement
before OLT. Although patients on MMT experienced greater perioperative
morbidity, overall long-term patient and allograft survival were similar to
other liver transplant recipients at our center. These patients show a degree of
compliance similar to other transplant recipients. In summary, patients with
ESLD on MMT should be considered for OLT after careful evaluation and
screening.
EDITORIAL IN LIVER TRANSPLANTATION
In this issue,
Kanchana et al report on five methadone maintenance patients who received liver
transplantation for liver failure caused by hepatitis and alcoholic cirrhosis
between 1993 and 1999. All of the patients had uneventful transplantation,
reasonable medication compliance, and good follow-up evaluation. All were
reported clear of illicit drugs and alcohol for the 6 months preceding
transplantation. They were on low doses of methadone, and thus it is fair to
assume that these patients were relatively stable and compliant with the
abstinence goals of methadone treatment. In all likelihood, they were what
physicians see as good patients, in concert with treatment goals and generally
compliant with medical recommendations for their overall care. So why is this
report significant? It is significant because it is the first to present
evidence, albeit small, in favor of accepting an increasing number of methadone
maintenance patients onto transplantation waiting lists. These patients are
maintained on methadone as treatment for comorbid opiate dependence and have
previously largely been excluded from transplantation without convincing
evidence supporting this a priori exclusion.
There are very few prior
reports in the literature describing transplantation outcomes of
opiate-dependent patients. Gordon et al2 reported that in 20 heroin users
receiving kidney transplants, there was no difference in graft survival, patient
survival, rate of infection, or loss of graft. Stevens et al3 reported excellent
results in 15 patients with opiate dependency in full recovery and concluded,
"the reformed heroin addict is a good candidate for renal transplantation." They
reached this conclusion despite finding that 10 of 15 patients were actively
smoking marijuana.
Although this is a small sample, this study signals a
shift toward evidence-based medicine as a basis for transplantation decisions in
recovering heroin addicts. This has happened previously in the transplant
community when the evidence supported transplantation for alcoholic
cirrhosis.
The Third National Health and Nutrition Examination Survey
(NHANES III) stated that an estimated 3.9 million US citizens (1.8%) have been
infected with hepatitis C virus (HCV). Chronic HCV results in an estimated 8000
to 10,000 deaths each year. Because the prevalence of HCV infection is
approximately threefold higher among people now between 30 and 49 years of age,
the number of deaths resulting from HCV-related liver disease will likely
increase substantially during the next two decades as this cohort reaches the
ages at which complications from chronic liver disease typically
occur.
The most frequent known vector for hepatitis C transmission is
needle-sharing in intravenous drug users, with heroin injectors as the
highest-risk group. According to the 2000 National Household Survey on Drug
Abuse,5 an estimated 130,000 individuals had used heroin in the 30 days before
the survey, and an estimated 2.8 million have used heroin at some time in their
lives. There are an estimated 600,000 regular heroin users in the United States,
but only approximately 175,000 are currently maintained on methadone maintenance
treatment (MMT).6 Chetwynd et al7 tested for hepatitis C in a sample of 116
opiate-dependent patients and found a prevalence of 84.2%. Thus the number of
HCV-positive MMT patients can be estimated at 150,000 at this point, and the
potential need for liver transplantation estimated at 7500 just from this
cohort. These estimates are, of course, based on in-treatment MMT patients; the
actual numbers of at-risk intravenous drug users are much higher.
Because
organs for transplantation are scarce, transplant centers have necessarily
turned to various models of organ allocation. Jonsen8 has described the
utilitarian model, the egalitarian model, and the social utility model. Only the
latter is an avowedly moral model, and the one most likely to impede addicts in
recovery from transplantation access.
The utilitarian model of medical
effectiveness strives to give organs to patients who will have the most medical
benefit based on studies of effectiveness. The basic tenet is that an organ
should not be "wasted" on a patient who is, for example, expected to die because
of another problem within a short time. This model has several shortcomings.
First, there is a lack (and unfeasibility) of clear studies about all of the
medical and psychosocial factors involved. Second, efficacy studies do not
necessarily answer the question about where to draw the line for acceptance on a
waiting list. For example, how does one choose between a young person with
hypertension and cardiac risk factors, and an older, relatively more healthy
individual? Third, earlier research may not take account of new advances in
immunosuppressant medications and other changes in practice.
The
egalitarian model recommends a random selection of recipients to ensure equality
and maintain the dignity of recipients. Shortcomings of this model include
practical problems, such as accounting for changes in acute medical status of
individual patients, new patients on the list with high urgency for
transplantation, and ethical disagreement over whether a "gift of life" should
be left to a lottery.
The social utility model attempts to find a
consensus about what characterizes a person as valuable for society and as
having earned the right for placement on a transplant list. The social utility
model is rarely used as the sole model in the United States; however, being the
only model acknowledging value judgments, it is likely to be included in others
models in a hidden fashion. Levenson and Olbrisch report results from a survey
of all cardiac, liver, and renal transplant centers. They found that nonmedical
reasons for rejection included a history of significant criminal behavior as an
absolute contraindication for 17.4% and a relative contraindication in 45.7% of
surveyed transplant programs. Corresponding exclusions for current federal
prisoners are 39.1% and 30.4%. When a patient is judged unlikely to protect the
graft because of a history of medical noncompliance, a variant of this moral
model is active. Another variation of this moral model is used when the question
of responsibility for the disease is discussed. It has been suggested that
patients who have inflicted the organ-destroying disorder on themselves should
be given lower priority over patients who became ill without any doing of their
own. However, this rule is inconsistently applied because noncompliance with
good medical advice is so ubiquitous in all patient populations. Many patients
on transplant lists have prior histories of high-cholesterol diets, poor
compliance with chronic medications, smoking, and other medical risk
factors.
Methadone is a medication, not an addiction. Although methadone
is most certainly an opioid that can produce physical dependence, its use by MMT
patients is not best conceptualized as an addiction, but as a replacement
medication. It is difficult to get high on it, it is not injectable, and the
evidence for its long-term efficacy is overwhelming. Properly prescribed
methadone is neither intoxicating nor sedating. It does not impair motor
activities such as driving. Methadone suppresses narcotic withdrawal and drug
craving for 24 to 36 hours, but patients still perceive pain and have emotional
reactions. Adequate doses, usually above 60 mg per day, competitively block
heroin effects and make "chipping" a waste of time and money. Above all, when
used in a structured treatment program, it leads to greatly improved social
functioning and not to the impaired functioning associated with heroin use.
MMT patients should not be excluded from transplant consideration.
Methadone should not be a proxy for other kinds of psychosocial evaluations.
Psychosocial factors remain important in eligibility assessment, but many
methadone maintenance patients meet criteria for adequate psychosocial support.
By complying with the very stringent rules of methadone programs, they have
shown their capacity to comply with complex requirements to an extent that can
rarely be matched by other transplant candidates. Requiring abstinence from
illicit substances before transplant is likely to increase compliance and
stability and has been shown to be an acceptable prerequisite. Belle et al19
report that criteria for recipient and donor selection change as centers gain
experience. It seems important to distinguish between MMT patients who have
turned their lives around from those who continue to use other illicit drugs,
participate in criminal or antisocial activities (such as domestic violence),
and remain psychosocially unstable. It is important that methadone not be
considered a proxy for these aspects of a psychosocial evaluation. In our
opinion, there are many MMT patients who should not be qualified for waiting
lists because of chaotic, criminal, drug-using lifestyles or other psychosocial
factors. Rather, it is that these factors need to be assessed in their own
right. Mandatory discontinuation of methadone should not be required.
Discontinuation of methadone, particularly when unsupported by a
residential treatment program such as a therapeutic community, is very likely to
produce heroin relapse in previously stable patients and thus disqualify them
for transplantation. The American Society for Addiction Medicine position paper
of 1990 states, "for the majority of opioid dependent patients, methadone
maintenance is the most effective long term modality. Withdrawal from methadone
carries a substantial risk associated with relapse to intravenous drug use.
Withdrawal should only be attempted when strongly desired by the patient and
with adequate supervision and support."20 The 1997 NIH consensus statement21
reports that "it is now generally agreed that opiate dependence is a medical
disorder and that pharmacologic agents are effective in its treatment" and
"continuity of treatment is crucialand most, if not all, patients require
continuous treatment over a period of years, and perhaps for life."
An
evidence base needs to be developed for MMT patients who undergo
transplantation. The experience with alcohol dependent patients shows that
substance abuse disorders per se are no reason for exclusion for liver
transplants. The implicit assumption that substance abusers will be noncompliant
or will simply relapse remains prevalent. It is also possible that judgments of
social value, which occurred in the alcoholic population, are even more salient
in the opiate addicts. They have a higher likelihood of criminal history, lower
social status, unemployment, and antisocial behaviors. It is, of course,
entirely possible that these patients are at higher risk for noncompliance, as
it was possible that alcoholics would resume drinking after transplant. At this
point, however, these reservations remain speculative and have no supporting
evidence in the literature. On the contrary, the few available reports,
including the small sample reported in this issue, indicate that outcomes for
MMT patients are no different than those fo the rest of the population.
Studies are needed to examine several kinds of outcomes-tolerance levels
for opioid analgesics postoperatively, medication compliance, misuse of opioid
analgesics, long-term graft outcomes, and overall compliance with medical
regimens. Because most of these patients will have liver failure caused by
hepatitis C, outcomes for MMT patients need to be compared with other cohorts of
similarly infected patients.
(SHORT-TERM METHADONE ADMINISTRATION REDUCES ALCOHOL CONSUMPTION IN
NON-ALCOHOLIC HEROIN ADDICTS (F. Caputo, et al)
Overview of the
diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV
FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C. by
Thierry Poynard , Francoise Imbert-Bismut , Mona Munteanu , Djamila Messous
, Robert P Myers , Dominique Thabut , Vlad Ratziu , Anne Mercadier , Yves
Benhamou and Bernard Hainque. Comparative Hepatology 2004,
3:8:10.1186/1476-5926-3-8 (http://www.comparative-hepatology.com/content/3/1/8)
