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Medical Writers' Circle

Liver Transplantation and Methadone

Meredith M. Hancock, B.A.,
Elana M. Craemer, B.S.,
Lorenzo Rossaro, M.D.

Liver Transplant Section, Department of Internal Medicine, University of California, Davis Medical Center

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Methadone is a highly effective treatment for opioid dependence. Unfortunately, methadone maintenance therapy (MMT) continues to be a barrier to standard medical care. Although there is no evidence-based medicine that would indicate that MMT patients have worse outcomes than non-MMT patients receiving liver transplants (LT), transplant programs continue to preclude patients undergoing MMT from transplantation.1,2 In a recent nationwide survey, just over half of responding transplant centers stated that they would consider active MMT patients for transplant waiting lists; however, one third of these centers still required patients to stop their methadone therapy prior to listing.3

At UC Davis Medical Center (UCDMC), MMT patients are evaluated for liver transplantation in the same manner as any other patient. All transplant candidates must undergo certain standard medical, surgical, psychosocial, and financial evaluations (see table 1).

Table 1: Psychosocial criteria for liver transplant candidacy.

Stable Mental Health

Appropriate Housing

Social Support Network

Adequate Income or Sufficient Medical Insurance Coverage

Basic Nutrition

Reliable Transportation

Abstinent from Alcohol or Illicit Drugs for a Sufficient* Period of Time

Objective Evidence of Good Compliance

Reliable Phone Availability

For example, when evaluating a patient’s psychosocial criteria, our team would consider living arrangements, communication, transportation, social support as well as the patient’s understanding and expectations of the transplant process. Additionally, patients with a history of substance abuse are required to sign an abstinence agreement, undergo random toxicology screenings, attend treatment programs (Narcotics Anonymous, Alcoholics Anonymous, MMT), and work with an addiction specialist as necessary. Toxicology screenings include barbiturates, benzodiazapenes, cocaine metabolites, opiates, cannabinoids, and ethanol.

Chronic hepatitis C Virus (HCV) leading to cirrhosis is the number one cause for liver transplant. Intravenous-drug use (IVDU) is the greatest risk factor for hepatitis C.1 It is well known that hepatitis C is highly prevalent in MMT patients.4 In fact, approximately 80-90% of this population test positive for HCV.2, 4 Since HCV is the most common cause for LT and the majority of MMT patients have hepatitis C, the need for an LT in the MMT population is greater than in most patient populations (see table 2).

Table 2: Methadone maintenance therapy (MMT)and Hepatitis C Virus (HCV).

Author Year Organ N= Comments
Sylvestre D et al.5 2004 NA 76 MMT patients can be successfully treated for HCV. 28% of 76 ex-heroin addicts had sustained virological response
McCarthy JJ & Flynn N4 2001 NA 460 MMT should not preclude patients from HCV treatment. 87% of the MMT patient population is HCV positive
Davis GL & Rodrigue JR8 2001 NA NA Patients enrolled in MMT programs are the best candidates for antiviral treatment because of their likelihood of compliance

Unfortunately, MMT patients are grossly underrepresented as transplant recipients (see figure 1). Figure 1 depicts the LT disparity between the HCV positive population and the MMT population: in other words, only a few MMT patients with HCV and End-Stage Liver Disease have the opportunity to be evaluated for LT.

 

Figure 1: An illlustrtion of the disparity between methadone maintenance therapy (MMT) and non-MMT patients with hepatitis C virus (HCV) in regard to liver transplant (LT). Area 1: shows that the majority of MMT patients do have HCV. Area 3: shows that the majority of LT patients have HCV. Area 2: is the small portion of MMT/HCV that receive LT.

 

Stigma regarding MMT continues to be a barrier to patients receiving liver transplant. Although methadone is a widely-accepted, highly effective treatment for opiate addiction, MMT patients continue to be discriminated against. The primary reason for this bias was investigated in a 2001 survey which showed that a majority of transplant centers required MMT cessation prior to LT. The general conclusion was that there was a signi-ficant misunderstanding between heroin abuse and methadone maintenance therapy as treatment.3

More specifically, methadone is often seen as an abused drug, not as a treatment for opiate addiction. Thus, MMT patients may still be perceived as not fully “recovered”; they are treated as if they are “addicted” to a drug (i.e., methadone) and are not “worthy or ready” for standard medical care, such as treatment of HCV and LT. The practice of requiring MMT discontinuation in order to receive a liver transplant may be considered unethical if not harmful; however, there is an emerging opinion supporting the cautious inclusion of MMT patients in liver transplantation (see table 3).6

Table 3: Collection of literature about methadone maintenance therapy (MMT) and liver transplants:

Author Year Organ No. Comments
Liu L et al.2 2003 Liver 36 Graft survival rates in liver transplant recipients were comparable between MMT and non-MMT patients
Di Martini A & Weinrieb R (Editorial) 6 2003 Liver NA MMT patients should be eligible for transplant
Kanchana TP et al.1 2002 Liver 5 MMT patients can successfully undergo liver transplants and should be considered if they meet the same psychosocial requirements
Koch M.& Banys P.3 2001 Liver NA MMT patients were accepted by 56% of the 87 liver transplant programs that responded to the survey

The NIH 2002 Consensus Statement on HCV management clearly supports methadone treatment for opiate addiction. The document states that methadone helps reduce risky behaviors and should not be used as a reason to exclude a patient from HCV treatment. In addition to standard combination therapy, one must consider LT as common treatment for HCV.

A substantial portion of MMT patients have a proven track record of medical follow up appointments, repeated laboratory studies, and adherence to taking their methadone. MMT patients with a history of drug and alcohol addiction can be successful in HCV treatment and they are expected to adhere to the LT immunosuppressive drug regimen. Some even suggest that compliant MMT patients are the best candidates for HCV therapy among IVDUs.8 At UCDMC, we recommend that patients on MMT needing a liver transplant should not be required to stop taking methadone. We believe that each patient should be evaluated independently and equally with respect to history and compliance behavior. Finally, MMT should not exclude patients from receiving LT.

 

References:

1. Kanchana TP, Kaul V, Manzarbeitia C, Reich DJ, Hails KC, Munoz SJ, Rothstein KD. Liver transplantation for patients on methadone maintenance. Liver Transpl2002 Sep;8(9):778-782.
2. Liu LU, Schiano TD, Lau N, O’Rourke M, Min AD, Sigal SH, et al. Survival and risk of recidivism in methadone-dependent patients undergoing liver transplantation. Am J Transplant. 2003 Oct;3(10):1273-1277.
3. Koch M, Banys P. Liver transplantation and opioid dependence. JAMA 2001 Feb 28; 285(8): 1056-1058.
4. McCarthy JJ, Flynn N. Hepatitis C in methadone maintenance patients: prevalence and public policy implications. J Addict Dis. 2001;20(1):19-31.
5. Sylvestre DL, Litwin AH, Clements BJ, Gourevitch MN. The impact of barriers to hepatitis C virus treatment in recovering heroin users maintained on methadone. J Subst Abuse Treat 2005;29:159-165.
6. DiMartini A, Weinreb R. Liver transplantation for methadone-maintained opiate dependents: making the case for cautious optimism. Am J Transplant 2003; 10:1183-1184.
7. NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements. 2002 Jun 10-12;19(3):1-46.
8. Davis GL, Rodrigue JR. Treatment of chronic hepatitis C in active drug users. N Engl J Med 2001 Jul;345(3):215-216.

 

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