Koch M, Banys P. Liver Transplantation and Opioid Dependence. JAMA. 2001;285(8):1056-1058. doi:10.1001/jama.285.8.1056
Author Affiliations: Department of Psychiatry, University of California at San Francisco and Mental Health Service, Veterans Affairs Medical Center, San Francisco. Dr Koch is now with Friends' Research Associates, Berkley, Calif.
Context Chronic hepatitis C is the leading cause for liver
transplantation in the United States. Intravenous drug use, the major
risk factor, accounts for approximately 60% of hepatitis C virus
transmission. Information from the United Network of Organ Sharing
(UNOS) does not address substance use among liver transplantation
Objective To identify addiction-related criteria for admission to
the UNOS liver transplantation waiting list and posttransplantation
problems experienced by patients who are prescribed maintenance
Design, Setting, and Participants Mail survey of all 97 adult US
liver transplantation programs (belonging to UNOS) in March 2000 with
telephone follow-up conducted in May and June 2000.
Main Outcome Measures Programs' acceptance and management of
patients with past or present substance use disorder.
Results Of the 97 programs surveyed, 87 (90%) responded. All
accept applicants with a history of alcoholism or other addictions,
including heroin dependence. Eighty-eight percent of the responding
programs require at least 6 months of abstinence from alcohol; 83%
from illicit drugs. Ninety-four percent have addiction treatment
requirements. Consultations from substance abuse specialists are
obtained by 86%. Patients receiving methadone maintenance are accepted
by 56% of the responding programs. Approximately 180 patients
receiving methadone maintenance are reported to have undergone liver
Conclusions Most liver transplantation programs have established
policies for patients with substance use disorders. Opiate-dependent
patients receiving opiate replacement therapy seem underrepresented in
transplantation programs. Little anecdotal evidence for negative impact
of opiate replacement therapy on liver transplantation outcome was
found. Policies requiring discontinuation of methadone in 32% of all
programs contradict the evidence base for efficacy of long-term
replacement therapies and potentially result in relapse of previously
Orthotopic liver transplantation is a standard treatment for end-stage
liver disease.1 In 1999, the United Network
of Organ Sharing (UNOS) coordinated 4698 liver transplantations in 97 adult
and 18 pediatric liver transplantation programs.2
As of May 2000, 15 258 patients were on waiting lists. Hepatitis C is
the leading cause of liver transplantation (46%), followed by alcoholic liver
disease (25%)3,4; both
are primarily substance abuse–related diagnoses. Approximately 2.7 million
persons in the United States are infected with hepatitis C virus (HCV).3,5 Twenty percent can be expected
to develop cirrhosis, 10% of those with life-threatening complications.6,7
The estimated lifetime heroin-dependence prevalence increased from 1.7
to 2.3 million from 1992 to 1998.8 The
most effective treatment is opioid replacement therapy,9
currently serving almost 180 000 patients in 785 programs.10
Studies expanding access to opioid replacement show promising results, making
office-based opioid replacement likely to be approved in the near future.11 The prevalence of HCV in intravenous drug users
in methadone maintenance therapy (MMT) is estimated at 84% to 90%.12,13 Thus, about 156 600
patients (or 5.8% of persons with HCV) are prescribed methadone. This subgroup
of potential liver transplantation applicants is likely to increase.
In 1993, Levenson and Olbrisch14
surveyed psychosocial criteria for acceptance into transplantation programs.
They found that "current use of addictive drugs" was considered an absolute
contraindication for 84% of liver transplantation programs. Use of addictive
drugs in the prior 6 months was not acceptable in 35.9% of the programs. They
did not address MMT or policies for opiate dependence.
After initial controversy, liver transplantation in alcoholic patients
is now well established.15 However, few
reports address transplantation outcomes of patients having other addictions.
Available UNOS data do not provide information about substance use among patients
requiring liver transplantations. Therefore, we sought to clarify general
practices and policies for patients with a history of substance dependence
by surveying the liver transplantation programs directly.
A survey questionnaire was mailed in March 2000 to all 97 adult liver
transplantation programs belonging to UNOS, followed by telephone contact.
Program coordinators were asked (1) Are patients with a history of substance
dependence accepted, and by whom are they evaluated (substance abuse professionals,
psychiatrists, social workers)? (2) Does the program require documented abstinence
and attendance in addiction treatment? (3) Is MMT acceptable or does the program
require discontinuation of methadone? How many MMT patients are on waiting
lists? and (4) How many MMT patients have received liver transplantations?
What problems were experienced?
Ninety percent (87/97) of programs responded. All said they accept patients
with a history of substance abuse and 86% obtain consultation by a substance
abuse professional or psychiatrist. Treatment requirements are assessed individually
by 60% for alcohol and by 55% for nonopioid illicit drug dependence. The most
frequently required duration of abstinence was 6 months (Table 1).
Of the responding programs, 56% accept MMT patients, but 32% require
that patients discontinue methadone use. Of the 28 programs requiring discontinuation,
22 obtain psychiatric/substance abuse consultations. Nine percent of programs
reported that no MMT patients had applied for transplantation and had no substance
abuse policies in place. Two percent gave no answer. Transplantation coordinators
estimated that 102 MMT patients were on a liver transplantation waiting list
in 24 programs. Thirty-nine responding programs described posttransplantation
experience with a total of 180 patients taking methadone. Only 9 programs
have experience with more than 5 such patients (Table 2 and Table 3).
Our survey indicates general acceptance for liver transplantation of
patients with a history of substance dependence, including opiate dependence.
Criteria for listing a patient on a transplantation waiting list are fairly
homogeneous. Patients currently enrolled in MMT were accepted by 56% of the
programs; however, only 10% had experience with more than 5 such patients.
The number of MMT patients who underwent liver transplantation was estimated
at 180, less than 0.5% of 40 468 liver transplants performed since 1988.2 The estimated 102 MMT patients on waiting lists
represent 0.7% of all patients, which seems low considering that 46% of all
liver transplantations are related to HCV.
Thirty-two percent of the responding programs require discontinuation
of prescribed methadone. This may indicate a clinical confusion between heroin
dependence as a problem and opiate replacement therapy as a medically supervised
treatment. Opiate replacement therapies are successful and well-documented
long-term treatment interventions for opioid addiction.9,16- 18
Discontinuation of methadone may result in relapse to illicit opiate use in
as many as 82% of stably maintained patients.18
It is noteworthy that discontinuation of methadone was required despite obtaining
consultation from addiction specialists in 24 of 28 programs. It is not clear
if consultants advised transplantation teams for or against continuation of
We found no reports in MEDLINE about liver transplantation outcomes
for opiate-dependent patients. Reports of kidney transplantation results in
former heroin addicts did not indicate poor outcomes.19,20
In our survey, only 3 of 39 programs (7 MMT patients) report their outcomes
as worse than for abstinent opioid addicts. Most programs report that the
posttransplantation course does not seem to differ from other transplantation
patients. In our survey, relapse rates for MMT patients appear low (<10%).
Immunosuppressant medication noncompliance seems higher (≤23%) than previously
reported in alcoholics (16%).21 However,
the 6 programs reporting some form of patient noncompliance found that transplantation
outcomes were not necessarily affected. Long-term methadone treatment does
not result in significant liver toxicity.22
Drug interactions are theoretically possible because tacrolimus and cyclosporine,
the most common immunosuppressants used in liver transplantation, as well
as methadone and Levomethadyl acetate hydrochloride, use the cytochrome P-450
No program reported drug interactions, and we found no reports of significant
clinical interaction in MEDLINE.
There are several limitations to this survey. No one knows the precise
numbers of MMT patients who apply for or receive liver transplantation or
reasons for rejection. Our survey relied on anecdotal information from the
liver transplantation coordinators; comprehensive psychosocial data were not
available. We did not collect information about marijuana/cannabis use, a
reported reason for rejection.
Opioid dependence is a problem that is frequently encountered in liver
transplantation programs. Systematic studies eventually led to greater acceptance
and improved access to transplantations among patients who are dependent on
alcohol.15 Interestingly, relapse rates
in alcoholic transplantation patients are reported as high as 30%,25,26 but the general outcome of
the transplantation is not usually affected. Alcohol relapse did not usually
result in noncompliance or compromised graft function. One possible explanation
may be that posttransplantation monitoring reduces the amount of alcohol patients
drink due to early interventions.26 Prospective
liver-transplantation outcome studies are needed for the growing population
of patients with comorbid opioid dependence and HCV to identify psychosocial
factors affecting the transplantation outcome and to examine the effect of
addiction treatment requirements. To help shape future transplantation policies,
we recommend that UNOS add addiction and MMT data to its database and monitor
treatment compliance and outcomes factors.
In the meantime, there is no evidence base to support the practice of
discontinuing methadone maintenance as a precondition for liver transplantation.
Such a policy may induce relapse in formerly stable patients and then, because
of this, may disqualify these patients for surgery.