Deciding liver transplant candidacy: tools of the trade

Authors


Liver transplantation (LT) is the only life-saving modality for patients with advanced liver disease. Because the introduction of the Model for End-Stage Liver Disease (MELD) and the Pediatric End-Stage Liver Disease (PELD) system, the waiting list death rate and median times to transplantation have decreased significantly (1). Moreover, despite a greater proportion of sicker and older candidates having received a liver transplant, patient and graft survival has remained unchanged in the past decade owing to improvements in patient selection, surgical techniques, immunosuppression and medical management (1). In spite of these advances, the fact remains that the number of patients requiring LT is greater than the number of available donors; therefore, candidacy for transplantation is determined by a multidisciplinary committee.

Multidisciplinary committees consist of hepatologists, transplant surgeons, social workers, nurses, psychiatrists and members of other medical and surgical subspecialties. The extent to which medical professionals in LT can adhere to their moral obligation of extending life and relieving suffering whenever possible is restricted by the fact that transplantation is not necessarily an entitlement. In fact, the access and allocation process in organ transplantation is guided by principles of equity and medical utility with concurrent application of the concept of justice. In a broad sense, this concept highlights the issue of fairness in distributing the benefits and burdens of a communal resource.

A typical LT candidacy assessment includes an evaluation for past or present alcohol or illicit drug addiction. In many instances the indication for LT is a disease process that may be directly related to an addiction as is in alcoholic liver disease. If the multidisciplinary committee functions in an objective and evidence-based environment, candidacy for LT should be rather uniform among transplant centres. The study by Kroeker et al. (2) demonstrates that many decisions are not necessarily evidence based but predicated on societal values.

Kroeker et al. (2), in this issue of Liver International, evaluated LT eligibility in the US and Canadian centres. All Canadian, and 10 of 43 American LT centres responded to the survey. It is important to emphasize only a small proportion of the US LT centres (23%) responded, therefore these LT centres that did respond may not be an adequate representative sample of all the US centres. The majority of centres were high-volume centres, with the median number of annual cadaveric transplantations 60. The current practice in the determination of the LT eligibility in certain patient groups was evaluated by the responses given on the questionnaire. The factors being investigated were HIV infection, alcoholic liver disease, Jehovah's witnesses, medical non-compliance, non-alcoholic substance abuse, prisoner status and the lack of social support.

Nearly all (93.8%) respondents in the current study indicated that their LT centres require 6-month abstinence policy along with evidence of successful alcohol counselling before LT. The reason behind any period of abstinence is two-fold – provide an opportunity for alcohol hepatitis decompensation to resolve and provide some measure of the candidate's motivation not to resume drinking alcohol. However, the duration of sobriety that is necessary to prevent alcohol recidivism is unclear, and may be more complicated than only a period of time (3–5). In a recent meta-analysis by Dew et al. (6), pretransplant factors that predicted alcohol relapse included social support, a family history of alcoholism and <6 months of abstinence. Other authors have argued a 3-month period may be sufficient in selected cases (7). Nevertheless, there does appear to be a general consensus in the necessity for such a period and based on this current study a 6-month period has been adopted and well accepted in both Canada and the US. Despite extensive evaluation of potential transplant candidates, as high as 50% of transplant recipients resume alcohol after surgery (8–10). A significant proportion of the heavy drinkers post-LT die from alcohol-related causes (8, 9).

Standard practice for most transplant centres in the US is to require abstinence from any illicit drug use with chemical dependency contracts and utilize random drug screening to document adherence. American and Canadian centres were also in agreement when it came to cocaine use. Most transplant centres in both countries felt cocaine use was at least a relative, if not absolute, contraindication to LT. The medical consequences of illicit drug use in LT recipients include direct drug-related health risks, alcohol-associated relapse, medication and non-compliance. Substance abuse or dependence has been found to be important predictors of alcohol relapse post-LT (11). The use of intranasal cocaine has been found to be a risk factor for hepatitis C transmission (12), which can be an important consideration in LT recipients. Cocaine use has also been associated with worse graft outcome in recipients of living related donors (13).

Unlike alcohol and cocaine, the use of marijuana use was perceived differently by American and Canadian centres. Seventy per cent of American LT centres perceived marijuana as an absolute contraindication as compared with 34% of the Canadian centres. This distinction between the two countries may have less to do with data suggesting worse patient or graft outcome, than with immediate societal perception. For instance, the evidence justifying marijuana as an absolute contraindication is scant. Several case reports and small case series have shown smoking marijuana was associated with aspergillosis infection and increased fibrosis rates with hepatitis C infection (14–17). In the US, the use of marijuana is illegal. There are proponents for the medical application of marijuana that have gained legality only in local legislatures; it is still a federal crime to be in possession. On the other hand, a recent Canadian poll revealed that over 50% of Canadians support legalization of marijuana (18). In fact, the Marijuana Medical Access Regulations in Canada were implemented in 2001, which allow individuals with terminal illnesses, HIV/AIDS, cancer, multiple sclerosis, epilepsy, spinal cord injury or disease and severe arthritis access to medical marijuana.

Another area of significant disagreement between the US and the Canadian evaluation is the approach to methadone-maintained (MM) candidates. In the study by Kroeker et al. (2), although none of the Canadian or American LT centres considered methadone a contraindication, 30% of the US transplant programmes felt potential transplant candidates must be off methadone before LT while only 16.6% of Canadian programmes shared that opinion. What can be a reason for the difference in transplant attitude? Methadone maintenance programmes are the mainstay for narcotic withdrawal and maintenance. In the US, there are over 180 000 individuals in Opiate Treatment Programmes (19). The majority of these individuals are in both maintenance and detoxification programmes. Despite the lack of evidence showing methadone is associated with any adverse effects, and the reported successful transplantation in select patients, most US LT programmes still consider methadone use a contraindication to LT (20). Consistent with the findings in Kroeker et al., a survey by Koch et al. (21) also found that approximately a third of the US programmes require discontinuation of methadone before transplantation.

In addition to exploring the practice patterns of LT centres in the US and Canada in dealing with issues of addiction and illegal substance abuse, in the study by Kroeker et al. (2), several other important issues such as non-compliance, lack of social support, criminal status and transplanting individuals who are unwilling to accept blood products and those with a positive HIV status were investigated. The published LT data regarding non-compliance and lack of support are limited. Interestingly, although there are no clear definitions in the scientific literature as to what constitutes medical non-compliance and lack of social support, there appeared to be significant concordance in practice patterns between the Canadian and American LT centres in dealing with these issues. Both issues were overwhelmingly perceived to be negative factors in the evaluation of LT eligibility. On the contrary, there was significant discordance in regards to the attitudes in assessing incarcerated patients for LT, 40% US centres as compared with 16.7% Canadian centres would not assess incarcerated patients. This difference in attitudes may be mainly owing to the fact that while Canada has a universal healthcare system, the US does not. However, despite that there is a fair number of LT centres in both countries that would assess incarcerated patients, to date there has not been a single report of a prisoner receiving a liver transplant. This is a very complex issue involving ethical, economical, social, medical and non-medical considerations.

Furthermore, two additional areas of controversy surround the issues of transplanting individuals who are unwilling to accept blood products and those with a positive HIV status. The decision of LT centres to find these factors as acceptable for LT hinges on whether these centres have the expertise to deal with the healthcare needs of these individuals. As more prospective, multicentre studies data become available and more LT centres become equipped to handle the medical needs of these individuals, the issue of whether or not to transplant these patients will become less controversial.

The intricacies of the ethical, medical and non-medical considerations that are integral to the transplant evaluation process make the task of constructing a universally accepted eligibility criteria to both access and allocation a particularly challenging one. Healthcare providers involved in the LT evaluation process have the responsibility of being good stewards of a scare resource, balancing their duty as individual patients' advocacy against the needs and limitations in society. The implication of a decision to place a candidate on the waitlist is that such a decision may directly result in the death on another individual on the waitlist. Of course, a denial is an almost certain sentence to death. These health professionals bear the burden of making such grave decisions, which are made complex by the many medical and non-medical factors involved in the transplant eligibility evaluation process.

Unfortunately, the scientific evidence can be conflicting or simply lacking in many areas in LT evaluation. Such limitations have produced the non-evidence-based practice patterns and transplant eligibility criteria that Kroeker et al. have identified. They compared the US and Canadian programmes and found some differences among those centres. Is it possible that these differences arise from there being a disparity in universal access to healthcare as it is the case in Canada but not in the US and/or from influences based on locality? In parts of the US do the concentrations of methadone clinics or local legislation regarding the use of marijuana have an impact on the surrounding LT candidacy? In fact, given the wide range of potential decisions that could be made, it is surprising that there is as much consensus as was found with regard to eligibility criteria.

Perhaps the major lesson that we should take away from this article by Kroeker et al. is that there is a major need for expanding the current scientific literature in regards to the medical consequences related to the following social issues: HIV infection, alcoholic liver disease, Jehovah's witnesses, medical non-compliance, non-alcoholic substance abuse, prisoner status and the lack of social support. With such data, it would be hoped that a more uniform consensus would emerge. It is unlikely that we will ever achieve complete agreement. However, we must ensure fairness in the transplant evaluation process by striving to practice evidence-based medicine and applying sound ethical judgment. Such honesty and transparency in the LT evaluation process should find acceptance in the general public.