Contemporary Policies Regarding Alcohol and Marijuana use Among Liver Transplant Programs in the United States.

Transplantation Publish Ahead of Print DOI: 10.1097/TP.0000000000001969

Contemporary Policies Regarding Alcohol and Marijuana use Among Liver Transplant Programs in the United States

Jiaming Zhu MD1, Ping-Yu Chen MD2, Marla Frankel LCSW3,

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Robert R. Selby MD3 and Tse-Ling Fong MD1,3

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From 1Division of Gastrointestinal and Liver Diseases, 2Department of Medicine

and 3 Liver Transplantation Program, Keck School of Medicine, University of Southern California, Los Angeles California USA

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Address correspondence to: Tse-Ling Fong, M.D.

Division of Gastrointestinal and Liver Diseases University of Southern California Keck School of Medicine

1510 San Pablo Street, 3/F

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Los Angeles CA 90033 USA Tel: 323.442 5908

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Fax: 323.442 6169 Email: [email protected]

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Copyright © Wolters Kluwer Health. Unauthorized reproduction of this article is prohibited.

AUTHORSHIP PAGE Jiaming Zhu: Collected, compiled and analyzed the data, wrote manuscript and approved final version. Ping-Yu Chen: Collected, compiled and analyzed the data, wrote manuscript and approved final version. Marla Frankel: Designed study, collected, compiled and analyzed data and approved final

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version.

Robert R. Selby: Analyzed data, wrote manuscript and approved final version.

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Tse-Ling Fong: Designed study, compiled and analyzed data, wrote manuscript and approved final version.

ABBREVIATIONS

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The authors have no conflicts of interest to declare.

AAH acute alcoholic hepatitis

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ALD alcoholic liver disease

MELD model for end-stage liver disease OLT orthotopic liver transplantation

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SRTR Scientific Registry of Transplant Recipients UNOS United Network for Organ Sharing

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Abstract BACKGROUND: Alcoholic liver disease is a common indication for liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period prior to OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in

policies regarding alcohol, marijuana and methadone use.

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the United States. This survey of liver transplant programs was conducted to evaluate current

METHODS: A questionnaire was distributed to 100 UNOS-approved liver transplant programs

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in North America that have performed at least 30 liver transplants/year in the last 5 years.

RESULTS: Forty-nine programs responded. Only 43% of programs required a specific period of abstinence prior to transplant for alcoholic liver disease and only 26% enforced 6-month

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abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors such as family support, patient’s motivation or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an

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additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of programs. CONCLUSIONS: Policies regarding alcohol use have become more flexible particularly toward

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patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.

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Introduction As of July 2nd, 2016, 14,628 candidates were registered on the liver transplant waiting list. In 2015, 7,127 liver transplants were performed in adults, 1422 patients died while waiting for a transplant and another 1473 were removed from the list due to being too sick to undergo transplant. Alcoholic liver disease (ALD) accounts for 19% of OLT performed in the U.S. (1). Patients with ALD generate more scrutiny regarding their candidacy since their liver disease is

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perceived to be a result of a ―voluntary health-risk behavior‖. Inclusion/exclusion criteria for OLT for patients with ALD are controversial and vary across liver transplant programs in the

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U.S. (2). For most programs, a 6-month abstinence period is a requisite to be on the liver transplant waiting list (3). The basis for the 6-month abstinence rule is to permit the chance for recovery of liver function in some patients who abstain. Data that support a lower recidivism

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rate among patients who have been abstinent for 6 months compared to patients with shorter abstinence period, are inconsistent (4).

Acute alcoholic hepatitis (AAH) represents a form of ALD due to ongoing alcohol use, often in the setting of binge drinking, which in its severe form that can be measured with various

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prognostic scoring systems and is associated with a poor short term prognosis (5-7). For a subset of patients with AAH, 30 day survival is less than 20%. In 2011, a European multi-center study showed that early OLT offered significant survival benefit to patients with severe AAH who did

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not respond to corticosteroids (8). We previously surveyed transplant programs in North America regarding policies for ALD patients and 94% of programs required a strict 6-month abstinent period prior to OLT (9). As such, patients with AAH would be ineligible for liver transplant in programs that adhere to the 6 month abstinence requirement.

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Since the last published survey of liver transplant policies regarding marijuana use, medical marijuana is legal in more than half of the states in the U.S. Concurrently, the number of states where recreational marijuana is legal is also growing.

The results of the European study showing the survival benefit of OLT for patients with AAH and legalization of marijuana in more than half of the U.S., prompted us to perform an updated

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survey of liver transplant programs in the U.S. regarding the alcohol, drug use and psycho-social

Material and Methods

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criteria for listing.

The 100 largest active UNOS-approved liver transplant programs in the last 5 years were

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selected for this survey. The questionnaire was initially distributed at the Society for Transplant Social Workers Annual Conference September 2013. In January 2014, the same questionnaire was then mailed to programs that had not responded. This questionnaire was designed to identify listing practices of programs for 5 different substance use/abuse diagnoses; alcoholic liver

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disease, acute alcoholic hepatitis, methadone use, medical marijuana and recreational marijuana use. The questionnaire also examined instruments that were applied to fulfill policy listing requirements for each specific program; alcohol or drink abstinence contract, formal

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rehabilitation program, mental health assessment, random toxicology screen and validated instruments to assess risk of relapse and psychosocial factors that were considered (See Supplemental Appendix, SDC, http://links.lww.com/TP/B495).

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Data regarding the 100 liver transplant programs, including transplant volume, waiting list death rate, transplant rates and outcomes, were extracted from Scientific Registry of Transplant Recipients (SRTR) database (10). Analyzing UNOS data from 1/1/2013 through 12/31/2014, the mean MELD scores for adult recipients of deceased donor liver transplants for that period for individual 11 UNOS regions were calculated. The national mean MELD was 23.3±0.1.

respond to the questionnaire.

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The characteristics of transplant centers that responded were compared to centers that did not Mean transplant volumes of responding and nonresponding

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programs, national average transplant rates and waiting list mortality rates were obtained from SRTR database. To determine possible associations regarding policies for alcoholic patients and marijuana use and program characteristics, programs were categorized based on volume of

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transplants (above versus below group mean), transplant rate (above versus below national average), waiting list mortality (above versus below national average) and UNOS region (above or below the national mean MELD for OLT).

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There were 5 programs that specifically requested anonymity and were not included in the analyses comparing characteristics of programs and policies. For the comparison of responding and nonresponding programs, these 5 programs were classified as nonresponders. However,

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responses of these programs are included in the overall results.

Statistical Analysis:

Descriptive statistics were calculated for all groups. Continuous variables were assessed using Student’s T-test. Dichotomous and categorical variables were assessed using Fisher’s exact test and the Chi-square test. Adjustment for multiple comparisons was done using the Bonferonni

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correction. The level of significance was set at P < 0.05. All calculations were performed using SPSS 22.0 statistical software (Armonk, NY).

Results Completed questionnaires were returned by 49 of the 100 invited programs. At least 2 or more programs from all 11 United Network Organ Sharing (UNOS) transplant regions responded. The

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following analysis was based on the number of responses received for each question; not all questions were answered by each responding center. The number of programs that responded to

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each question is listed following each sub-heading. Among responding centers, there was a higher representation of centers from the West and a lower representation from centers from the Northeast regions. Otherwise, the characteristics of responding and nonresponding centers with

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respect to transplant volume, waitlist mortality, transplant rate and outcomes, were similar (Table 1).

Alcoholic Liver Disease (number of programs: 49)

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Twenty-one programs (43%) required a specific period of abstinence before a patient with alcoholic disease could undergo liver transplant evaluation. Of these, 13 programs required 6 months, 5 programs required 3 months and 3 programs did not specify the required period of

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abstinence. All but 1 of these 21 programs also required a minimum 6 month period of abstinence prior to listing. Of the 28 programs that did not require a specific period of abstinence before evaluation, 23 required variable periods of abstinence before transplant listing; (range 1.5 - 6 months, median 6 months). Overall, only 5 (10%) programs will evaluate and list alcoholic patients without specified period of abstinence. Although more than half of programs will evaluate patients

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without a 6-month abstinence period, most programs will list patients only after a 6 month period of abstinence. There was no association between geographic or MELD regions for alcohol abstinence policies. However, the second highest quartile of centers with respect to transplant volume were more likely to require a specific alcohol abstinence period compared to other

Acute Alcoholic Hepatitis (AAH) (number of programs: 48)

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quartiles show data (82% vs. 33%; p=0.03).

For patients with acute alcoholic hepatitis, 34 (71%) programs would waive the 6-month

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abstinence requirement prior to transplant. One of the programs would still require at least 1 month of abstinence while another required at least a 3-month period of rehabilitation. Of these programs, 25 would otherwise have imposed a 6-month required period of abstinence for non-

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AAH patients prior to listing for transplantation, 3 would otherwise have a required a 3-month period, and 6 did not specify the period of required abstinence prior to listing. Among the 34 programs that waived 6-month sobriety requirement for AAH, other factors that were considered included: young age, high MELD>40 or acute liver failure, new onset hepatic decompensation

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without prior history of being told to stop drinking, absence of prior failed rehabilitation attempts, or if patient had other underlying causes of end-stage liver disease. Policy regarding transplantation of AAH patients was not affected by center characteristics including transplant

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volume and rate relative to national averages and location of center with respect to geographic or UNOS region.

Methadone Use (number of programs: 44) Twenty (45%) programs would transplant patients who were taking methadone. Three (7%) programs would not consider patients who were taking methadone. Thirty-seven (84%) programs

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would evaluate patients who were on methadone prescribed by a physician although 17 of these programs required tapering or discontinuing methadone before listing; specifically, 5 recommended discontinuing methadone use before transplantation, 7 tapered on a case-to-case basis, 4 would taper to a ―minimum‖ if patient cannot completely discontinue use and 1 program would taper to less than 50mg per day. Four (9%) programs would consider patients taking methadone on a ―case-by-case‖ basis and 1 program would only consider methadone users,

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which is prescribed for pain management and not for heroin addiction. Three programs that would evaluate methadone users declined to answer whether tapering or discontinuing

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methadone was required before listing/liver transplantation.

Medical Marijuana Use (number of programs: 47)

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Programs were asked if they accepted patients on the OLT waiting list who used medical marijuana if they had a medical marijuana card. At the time of the survey, medical marijuana was legal in 19 states. Thirteen programs (28%) marked ―not applicable‖ as their state did not have legalized marijuana (NY, OH, IL, GA, FL, NC, UT) at the time of the survey. After the

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survey, Illinois and New York legalized medical marijuana use in 2013 and 2014, respectively. Nineteen programs (40%) would not accept any marijuana use. Two programs, both in UNOS region 8 where medical marijuana is not legal, adopt a ―don’t ask, don’t tell‖ policy and patients

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were not asked about their use of medical marijuana prior to liver transplant listing.

Eighteen programs would consider patients using medical marijuana of which 13 programs would list patients using medical marijuana, but patients were required to discontinue use and test negative on drug screen for marijuana before OLT. Another program would list patients using marijuana provided marijuana is not smoked but it was unclear if they would consider

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transplant with continued use. Four programs would consider patients using marijuana on a caseto-case basis.

Recreational Marijuana Use (number of programs: 46) At the time of the survey, recreational marijuana was legal in Alaska, Colorado, Oregon, and Washington. Thirty-three programs (72%) would not accept recreational marijuana use. Thirteen

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programs responded that they would accept patients who used recreational marijuana, although 5 said they would allow this on a case-by-case basis, 1 require that the patient quit marijuana use at

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least 3 months before OLT and to undergo 12-step program.

Seven programs would accept both medical and recreational marijuana use, although 3 programs

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would consider them on a case-to-case basis. Eighteen programs would not consider patients for liver transplant who are using medical or recreational marijuana. Eight programs would consider patients using medical marijuana but not recreational marijuana. Programs from the lower tercile of MELD score at time of transplant UNOS regions were more likely to allow marijuana

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use compared to programs which transplanted at higher MELD score UNOS regions(p=0.004).

There was no association with the location of programs in states where medical and/or

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recreational marijuana is legal and the marijuana policies. The proportion of transplant programs which permitted (medical and/or recreational marijuana use in marijuana-legal states versus states where marijuana was not legalized (38.4% vs. 24%, p=ns). Summary of policies regarding patients and alcohol, methadone and marijuana use is shown in Table 3. There was no relationship between centers’ alcohol, marijuana or methadone policies.

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There has been a 3-fold increase in opioid overdose-related deaths between 1999-2014 which has disproportionately impacted states in the Northeast, Midwest and Southwest (11). However, there was no significant difference in mean transplant rate (57.1 vs. 58.0 people/year receiving OLT) nor mean annual transplant volume (64.7 vs. 57.7) among responding programs from these states compared to the rest of the country. Also, there were no significant statistical differences in policies regarding mandated period of alcohol abstinence (61.1% vs. 34.8%), waiver of 6

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month abstinence for AAH (66.7% vs. 68.2%), and acceptance of marijuana use (37.5% vs.

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22.7%) between programs from opioid affected states and the rest of the country.

Alcohol and Drug Abstinence Contract (number of programs: 49)

Thirty-nine programs (76%) required a signed alcohol and drug abstinence contract from

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patients. However, among these 39 programs, 2 imposed this requirement only in patients who had a positive toxicology screen, 2 required a contract for alcohol abuse only, 1 required a signed contract only if patient cannot undergo rehabilitation prior to transplant due to medical reasons,

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and 1 program if insurance is Medicaid.

Formal Rehabilitation Program (number of programs: 49) Completion of formal rehabilitation program is required by 46 (94%) programs. Majority of

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programs set guidelines for rehabilitation based on the period of sobriety that patients had achieved at the time of liver transplant evaluation. One program required rehabilitation for patients who were abstinent for less than 5 years, 1 required rehabilitation for less than 4 years, 1 for less than 3 years, 8 for less than 2 years, 4 for less than 1 year, 11 for less than 6 months, and 5 on a case-by-case basis. Five programs required rehabilitation for all alcoholic patients, irrespective of the duration of sobriety or other psycho-social factors. Seven programs required

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rehabilitation for patients who were deemed to have a high risk of relapse. Two programs required rehabilitation if patient was dependent on alcohol. One program did not specify their reason for rehabilitation.

Psychosocial Factors (number of programs: 49) Three programs were absolute with respect to the 6-month abstinence rule without consideration

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for other psychosocial factors. Eight programs said they would still consider special circumstances in which the patient may not live for 6 months or has other comorbidities such as

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HCC. Two programs also differentiated between ―active‖ drinking and ―casual/social‖ drinking and said that they would be more likely to list patients in the latter despite a short abstinence

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period.

Programs were asked which psychosocial factors were taken into consideration if the 6-month abstinence period was waived (Table 2). Strong family support was the most common factor taken into consideration followed by the patient’s motivation or commitment to reform and

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undergoing the transplant process. The importance of these psychosocial factors was rated on a scale from 1-5 by programs (Figure 1). Patients’ insight into alcohol use and their liver disease was the most important psychosocial factor considered by programs followed by strong family

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and social support system.

Mental Health Assessment (number of programs: 48) Nineteen (40%) programs required all patients with alcohol related liver disease to undergo evaluation by a psychiatrist or psychologist. One program required mental health evaluation,

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only in patients with ―moderate risk‖ of relapse. Twenty-nine (60%) did not routinely require mental health evaluation.

Random Toxicology Screens (number of programs: 49) Twenty-two (45%) programs required random toxicology screens in all patients. Additional 12 (24%) programs performed toxicology screens in ―high risk patients. High risk patients was

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defined by various criteria including recent alcohol use, high relapse potential, strong history of

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substance abuse, duration of abstinence ranging from less than 6 months to less than 2 years.

Use of Instrument to Assess Risk of Relapse (number of programs: 48)

Thirty-eight (79%) of the 48 programs did not use any validated instruments to assess risk of

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relapse in alcoholic hepatitis patients. Ten of the remaining programs used instruments: 1 did not specify, 2 used the Michigan Alcoholism Screening Test (MAST) or the CAGE, 1 used the Alcohol Use Disorders Identification Test (AUDIT), 1 used AUDIT and MAST, 1 used AUDIT and the National Institute on Drug Abuse Quick Screen (NIDA), another used the Stanford

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Integrated Psychosocial Assessment for Transplantation (SIPAT) only, 1 used the Psychosocial Assessment of Candidacy for Transplantation (PACT) only and 1 used HR Scale only. Of the 2 programs that used either CAGE or MAST, 1 program responded that they preferred CAGE over

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MAST.

Discussion

Our study highlights the changes and variability of policies pertaining to alcohol, marijuana and methadone among programs that are not related to UNOS region or size of the program. Alcoholic liver disease is one of the more common indications for liver transplantation. Previous

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surveys conducted in the U.S. (12), United Kingdom (13) and France (14), showed an unfavorable sentiment toward patients with alcoholic liver disease compared to patients with other forms of liver disease.

In one survey, prisoners were the only group felt to be less

deserving of liver transplant than patients with alcoholic liver disease (15). But a survey of public opinion conducted among 503 participants in 2015, showed that more than 80% people were at least neutral toward early transplantation for patients with acute alcoholic hepatitis (16).

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Historically, the majority of North American liver transplant programs required a 6-month abstinence period from alcohol use prior to liver transplantation (2-4,9,13-15,17-18). The basis

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for 6-month abstinence was to identify patients who may recover from liver decompensation obviating the need for OLT and to select patients that were more likely to be abstinent (19,20). However, the accuracy of the 6-month abstinence before transplant in predicting sobriety after

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transplant is controversial (19-21).

The European study that showed a significant survival benefit of early OLT in patients with severe AAH who were unresponsive to corticosteroids directly breached the 6 months-abstinence

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rule previously traditionally enforced by most programs (8). Our current survey showed that policies for listing and transplantation of patients with alcohol liver disease were more flexible compared to those described previously (2,3,9,17,18). Although the majority of programs

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formally required completion of rehabilitation, this was selectively enforced. Evaluation by psychologist/psychiatrist for patients with alcohol and drug use history was required by less than half of the programs. Only 43% of the programs required a specific period of abstinence before a patient with alcoholic liver disease could undergo evaluation but 75% of programs still required a 6-month period of abstinence prior to liver transplantation for patients. However, for patients with acute alcoholic hepatitis, 71% of the programs waived the 6-month abstinence and

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took into consideration psycho-social factors such as family support, insight and motivation demonstrated by the patient. Despite the potential for higher incidence of relapse, few programs incorporated validated instruments to determine the risk. A recent U.S. single center experience validated the survival benefit of early transplantation for patients with severe acute alcoholic hepatitis. Patient selection was based on specific psycho-social factors identified in our current

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survey (21).

Surprisingly, there was no association between alcohol policies and location of the transplant

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center, the availability of liver organs as evidenced by wait list mortality and rate of liver transplant. Our study did not evaluate outcomes of patients who had alcohol recidivism after liver transplant. A prior French study showed that graft and patient survival were comparable

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between relapsers and patients who remained abstinent after OLT (22). However, a more contemporary study, also from France, showed contradictory results. Recurrent alcoholic cirrhosis, which developed in 32% of patients with severe relapse after OLT, was associated with a significantly decreased survival. Furthermore, this study showed that relapse was more likely

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among patients with a shorter period of abstinence and who were younger (23). With an increased number of U.S. programs foregoing 6-month abstinence prior to OLT, predictors of recidivism and long-term outcomes of patients with history of alcohol use are areas that warrant

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further investigation.

In 2015, 58% of Americans surveyed favored legalization of marijuana (25). Medical marijuana is legal in over half of the states in the U.S and the number of states that is legalizing recreational marijuana is also growing. Eight states passed legislation that prohibits withholding transplant evaluation for marijuana users solely based on their marijuana use (26). Marijuana use is one of

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the more controversial factors in consideration for liver transplant eligibility (27-30). Marijuana is associated with temporary short-term memory loss, which raises concern for compliance with immunosuppression (29). Marijuana users were more likely to use tobacco or other drugs (30). There have also been isolated reports of adverse (pulmonary aspergillosis, being the most common) events, associated with marijuana use (31-35). However, a single-center retrospective study comparing 155 marijuana users to 1334 nonusers found no difference in patient survival

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after transplant (30). In our current survey, 16% programs would transplant patients who used marijuana while 14% programs categorically rejected such patients. The remaining 70% of

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programs viewed patients who used medical marijuana more favorably than recreational users. Interestingly, several respondents in our survey from states where medical marijuana was not legal, adopted a ―don’t ask, don’t tell‖ policy. Current program policies were in sharp contrast to

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prior study where marijuana use was an absolute contraindication among 70% of U.S and Canadian programs surveyed (9). A recent study among cardiac and lung transplant providers found that nearly two thirds of respondents supported listing patients using legal medical marijuana, but only 28% did so for patients using recreational marijuana. In states that have laws

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prohibiting marijuana use, respondents reported denying all marijuana using patients or mandating abstinence prior to transplant listing (28).

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Compared to prior surveys, there had been no significant change in policies regarding methadone use (9,36). The proportions of program that permitted patients to remain on methadone at the time of liver transplant remained constant. In our current study, 7% of the programs did not consider patients on methadone and 30% of programs required discontinuation of methadone by the time the patient underwent OLT. Small single-center studies on the outcomes of liver transplantation among methadone users showed a reduced risk of opioid relapse but more

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complicated pain management and higher intra- and post-operative requirement of anesthesia (37-39). Overall, long-term outcomes of methadone-using and nonmethadone liver transplant recipients were comparable (37, 38, 40). Despite these results, it appears that transplant centers were still hesitant to consider methadone users (37, 38).

There are several important aspects of our study compared to previous publications. The survey

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was conducted after compelling evidence for the benefit of OLT for patients with AAH who have not necessarily fulfilled the 6-month abstinence period. These findings may have

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contributed to more flexible policies of programs toward patients with alcoholic liver disease. The number of states that have legalized marijuana (medical and/or recreational) use since prior surveys has increased significantly. Although geographically the proportion of programs from

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the Northeast was under-represented and the Western states were over-represented, this study includes programs from all 11 UNOS regions. As a result, this survey included a greater proportion of programs from regions with higher MELD scores at time of transplant and underrepresented regions that are impacted by the increase in opioid-related deaths with higher access

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to organ donors. On the other hand, marijuana is not legal in most of the Southern states. There was a suggestion from this study that programs from the Northeast and South were more lenient in permitting marijuana use compared to the rest of the country but the number of responding

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programs is too small to potentially show a difference. We can only speculate that policies concerning marijuana use among individual programs are dictated by multiple factors besides organ accessibility which may include local laws and social norms in different parts of the country.

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There were considerable variations and no consistent associations with policies and transplant program characteristics. The number of responding centers may not be sufficient to observe possible associations. Nevertheless, this response rate for this survey is comparable to other voluntary surveys of transplant programs (2,3,9,18,28). Practically, to obtain a higher rate of response, such surveys will have to be administrated through UNOS and/or Centers for Medicare and Medicaid Services, agencies that regulate and oversee transplant programs in the U.S.

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Another limitation to our study is our inability to obtain clarification of sometimes inconsistent

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responses.

Although, the eligibility of a transplant recipient is at the discretion of individual programs, there are intervening parties that influence these policies including medical insurance payors and state

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laws; 7 states have enacted laws barring programs from denying organ transplants to patients solely on the basis of medical marijuana use (26). Indeed, there is no overwhelming scientific data that support not transplanting marijuana use, although evidence is limited to a single center

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study (30). The effect of marijuana use on outcomes after liver transplant warrants more study.

Policies pertaining to alcohol use and eligibility for liver transplantation have changed in the last decade. The benefit of liver transplantation in patients with acute alcoholic hepatitis who have

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not responded to corticosteroids highlights the potential obstacle of the strict 6-month abstinence rule. This survey showed that most programs will take into consideration psycho-social factors regarding liver transplantation and forgo the 6-months rule for patients with acute alcoholic hepatitis. Patients using marijuana are currently accepted among many liver transplant programs in keeping with the legalization of marijuana in many parts of the United States. However, there remains a lack of uniformity of policies regarding alcohol and marijuana use. Further studies are

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required to determine whether relaxation of the 6-month rule is associated with a higher rate of recidivism and difference in graft and patient survival. These studies will provide clinical

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evidence to shape policies regarding alcohol and marijuana use.

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http://www.gallup.com/poll/186260/back-legalmarijuana.aspx?utm_source=genericbutton&utm_medium=organic&utm_campaign=shar

A

ing. Published October 21, 2015. Accessed November 26, 2016,

26. http://leginfo.legislature.ca.gov/faces/billNavClient.xhtml?bill_id=201520160AB258&se arch_keywords=

27. Neyer J, Uberoi A, Hamilton M, Kobashigawa JA. Marijuana and Listing for Heart Transplant: A Survey of Transplant Providers. Circ Heart Fail. 2016;9:e002851

22


28. Secunda K, Gordon EJ, Sohn MW, Shinkunas LA, Kaldjian LC, Voigt MD, Levitsky J. National survey of provider opinions on controversial characteristics of liver transplant candidates. Liver Transpl. 2013;19:395–403. 29. Coffman KL. The debate about marijuana usage in transplant candidates: recent medical evidence on marijuana health effects. Curr Opin Organ Transplant. 2008;13:189–195.

candidates. Am J Transplant. 2009;9:280–285.

D

30. Ranney DN, Acker WB, Al-Holou SN, et al. Marijuana use in potential liver transplant

31. Hamadeh R, Ardehali A, Locksley RM, York MK. Fatal aspergillosis associated with

TE

smoking contaminated marijuana, in a marrow transplant recipient. Chest. 1988;94: 432– 433.

32. Marks WH, Florence L, Lieberman J, Chapman P, Howard D, Roberts P, et al.

EP

Successfully treated invasive pulmonary aspergillosis associated with smoking marijuana in a renal transplant recipient. Transplantation. 1996;27:1771–1774. 33. Soubani AO, Qureshi MA. Invasive pulmonary aspergillosis following b1 marrow transplantation: risk factors and diagnostic aspect. Haematologia (Budap). 2002;32:427–

C C

437.

34. Vethanayagam D, Pugsley S, Dunn EJ, Russell D, Kay JM, Allen C. Exogenous lipid pneumonia related to smoking weed oil following cadaveric renal transplantation. Can

A

Respir J. 2000;7:338–342.

35. Sánchez Lázaro IJ, Almenar B1t L, Sancho-Tello MJ, Martínez-Dolz L. Ventricular tachycardia due to marijuana use in a heart transplant patient. Rev Esp Cardiol. 2009;62:459–461. 36. Koch M, Banys P. Liver Transplantation and Opioid Dependence. JAMA. 2001;285:1056-1058.

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37. Weinrieb RM, Barnett R, Lynch KG, DePiano M, Atanda A, Olthoff KM. A matched comparison study of medical and psychiatric complications and anesthesia and analgesia requirements in methadone-maintained liver transplant recipients. Liver Transpl. 2004;10:97-106. 38. Kanchana TP, Kaul V, Manzarbeitia C, Reich DJ, Hails KC, Munoz SJ, Rothstein KD. Liver transplantation for patients on methadone maintenance. Liver Transpl. 2002;8:778-

D

782.

39. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving

TE

maintenance methadone or buprenorphine therapy. Ann Intern Med. 2006 ; 144:127–134. 40. Liu LU, Schiano TD, Lau N, et al. Survival and risk of recidivism in methadone-

A

C C

EP

dependent patients undergoing liver transplantation. Am J Transplant. 2003;3:1273-1277.

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D TE EP C C A 25


Table 1. *Characteristics of Responding Versus NonResponding Centers Responder (n=44)

P-value 0.004

4 (7.1) 11 (19.6) 16 (28.6) 25 (44.6)

60.6 (18-149)

72.1

16.8 (7.3-37.8)

18.3 (8.2-36.1)

0.282

57.6 (6.7-207.4)

77.1(11.5-247.4)

0.063

(23/44) 52.3%

(24/56) 42.9%

0.421

97.7%

98.2%

NS

D

0.177

EP

Mean Liver Transplant Volume (number/year) (range) Mean Waiting List Mortality (%) (range) Mean Transplant Rate (people/year receiving OLT) (range) Programs in UNOS regions transplanting above national mean MELD score (%) Outcome (% “As expected”)

14 (31.8) 12 (27.2) 7 (15.9) 11 (25.0)

TE

Geographical Region Number (%) West Midwest Northeast South

Nonresponder (n=56)

*There were 49 centers that responded, but 5 insisted on anonymity. These 5 programs were

A

C C

classified as nonresponders for this comparison

26


Table 2. Psycho-social factors considered when 6-month abstinence is not required (Programs could provide more than 1 factor)

6 5

TE

4 4 4 4 3 3 2 2 2

D

Number of programs 30 12 9 9 8

EP

Psychosocial Factors Family support Motivation Insight Mental health Previous rehabilitation/attempts at sobriety Coping skills No impairment of function related to drinking (relationship, legal) Employment No prior knowledge of liver disease Presence of polysubstance use Young age Financial security Never told to quit Having young children Insurance coverage Ability to follow through with rehab after transplant Family history of alcoholism

A

C C

1

27


Table 3. Summary of alcohol, marijuana and methadone policies among liver transplant programs Policies

Percent of Responding Programs* 41

Require 6-months alcohol abstinence Waive 6-months alcohol abstinence for

69

patients with acute alcoholic hepatitis 76

Completion of formal rehabilitation for patients with history of alcohol/substance abuse

94

Random toxicology testing

D

Require alcohol and drug abstinence contract

TE

69

Use of validated instrument to determine risk of relapse

21

Exclude methadone use

55

Exclude medical marijuana use

72

A

C C

EP

Exclude recreational marijuana use

40

28


1. Name of transplant program that you work for?

D

2. Does your program require a specific period of abstinence before a patient is evaluated for a liver transplant? No Yes If yes, what is the period? 3. Does your program require a specific period of abstinence before a patient is listed for a liver transplant? No Yes If yes, what is the period of abstinence?

TE

4. Does your program consider patients with acute alcoholic hepatitis for liver transplant if he/she has not been abstinent for at least 6 months? No Yes If yes, what are the circumstances?

EP

5. Are your patients required to sign a contract agreeing to remain abstinent from alcohol and/or illicit drugs?

6. Does your program require patients to complete a formal rehabilitation program? If so, Is it required for all patients who have abused alcohol irrespective of period of abstinence?



Is it only required only for those patients who have been abstinent for less than 6 months?

C C





Is it required only for those patients who have been determined to be high risk for relapse?

A

7. What psychosocial factors are taken into consideration if the 6 month abstinence rule does not apply?

8. Based on your discussions at your program Selection Committee, please rate the following psychosocial factors, on a scale of 1-5, with respect to their importance of maintaining sobriety. 1-

not important

2- somewhat important

3- moderately important

4- very important 5- most important

a. Strong family/social support system b. Having stable employment

29


c. Insight into the impact that alcohol has had on one’s health d. Ability to identify appropriate coping skills e. Completion of a formal rehabilitation program (includes Alcoholics Anonymous)

f.

Failed rehabilitation attempts

h. Involvement in one’s religious community i. Having outside interests such as hobbies

D

g. Past relapses

TE

9. Are all patients with alcohol related liver disease evaluated by a psychiatrist? No Yes

EP

10. Are patients with alcohol related liver disease given random toxicology (drug) screens? No Yes If yes, which patients are tested?

C C

11. Does you program require a patient who participates in Alcoholics Anonymous to have a sponsor? No Yes 12. Does you program use a specific instrument to assess risk of relapse? No Yes If yes, which instrument?

A

13. Does your program accept patients on the liver transplant waiting list who are taking methadone prescribed by a physician?

14. If so, are they required to taper down or ultimately discontinue using it before the transplant?

30


15. Does your program accept patients on the liver transplant waiting list who use medical marijuana, if they have a medical marijuana card?

16. If so, are they required to discontinue using marijuana before being listed?

A

C C

EP

TE

D

17. Does your program accept patients who use recreational marijuana?

31


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Prevalence of alcohol-interactive prescription medication use among current drinkers: United States, 1999 to 2010.

Variability of Brain Death Policies in the United States.

The Risk of End-Stage Renal Disease Among Living Donor Liver Transplant Recipients in the United States.

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