Alcoholic Liver Disease and Transplantation : Ethical Issues

by National Institute of Health

(Page 7 of 7)

Researchers and clinicians originally thought that ALD patients would have poorer graft and patient survival rates than non-ALD patients, but such a difference has never been documented. Neither has the assumption of high relapse rates in ALD patients been confirmed. Relapse rates following OLT are lower than in patients undergoing alcoholism treatment, and serious relapses that adversely affect the transplanted liver or the patient are uncommon. In contrast, patients who receive OLT because of an infection with hepatitis B or C viruses always experience disease recurrence and have an increased likelihood of losing the transplanted liver primarily because of this recurrence. Another concern, that patients with ALD would not be able to comply with the antirejection medication regimen, also has not been confirmed. Graft-rejection rates are similar for patients transplanted for ALD and those transplanted for other types of liver disease, which indicates comparable rates of compliance with the antirejection medications. Finally, it was anticipated that ALD patients would utilize more resources, thereby incurring higher costs, than non-ALD patients, but again this assumption never has been corroborated by research evidence.

In contrast to these negative assumptions regarding the outcome of OLT in ALD patients, many clinicians argue that ALD is an excellent indication for liver transplantation. For example, the overall improvement in the status of patients with ALD after OLT, including the improvement in productivity, supports considering such patients for liver transplantation. Moreover, the long-term costs of OLT and the subsequent management of the alcoholic patient probably are lower than the costs of managing alcoholism and ALD without transplantation. This assumption is based on the observation that only 22 percent of all alcohol-dependent people seek help within any 1-year period, and fewer than one drug abuser in eight receives formal treatment for alcohol or other drug dependence.

The suitability of ALD patients for OLT also must be considered in the context of the three principles of organ and tissue allocation identified by UNOS. First, the principle of medical utility requires that organs be allocated to those patients who are likely to experience the maximum medical benefit. This requirement is well satisfied by patients with ALD. Second, the principle of justice requires that equal respect and concern be given to all patients in need of an organ or tissue. This principle generates some ethical questions regarding the potential wastage of organs by transplantation in patients who may "voluntarily" revert to alcoholism. Third, the principle of autonomy requires that the personal choices of the patients be respected. In this regard, the UNOS Ethics Committee holds the view that a person's past behavior (including alcohol consumption) should not be considered as an exclusion criterion for OLT.

There is no one-to-one correlation between alcoholism and ALD. Only a minority of alcoholics develop ALD and may require OLT; conversely, many patients diagnosed with ALD do not meet the criteria for alcoholism. However, the indiscriminate allocation of a donor liver to an alcoholic who may relapse and thus endanger the function of the transplanted organ is not justifiable to the general public. It is important to remember that the general public makes up the donor pool and may be discouraged from organ donation by a policy of equal transplantation for alcoholics and nonalcoholics. Thus, clinicians must make an effort to identify OLT candidates among the ALD patients who are at low risk for relapse. Moreover, additional education of the public is necessary to displace the stigma for OLT in alcoholics and to increase organ donation.

Future Directions

Because outcome after liver transplantation, particularly the risk of relapse, is such an important concern in patients with ALD, identifying the factors that could indicate the most suitable candidates for OLT is a highly desirable goal of research. The following lines of inquiry show promise in this regard:

Studies have identified genetic characteristics that influence alcohol intake. Additional in-depth analyses are needed to determine the specific influences of these genes on the development of ALD or on the risk of alcohol relapse after OLT.

Genetic factors may determine a person's susceptibility to developing liver damage after alcohol consumption or to becoming alcohol dependent. Such possible factors should be investigated further, because transplanting a new liver might alter or negate the genetic influence. For example, a patient with a high susceptibility to ALD might not be as susceptible to ALD after OLT even if he or she returned to heavy drinking because the new liver would be governed by its own set of genetic factors. Conversely, if genetic factors determining alcohol metabolism by the liver play a role in maintaining alcohol dependence, then OLT might "cure" the addiction.

Researchers must develop better means of identifying ALD patients who are at risk of relapse after OLT. With better identification methods, transplant centers could focus their resources on this rather small group of patients before OLT in an effort to prevent subsequent relapses. Furthermore, research assessing various treatment programs may identify those approaches that best improve abstinence rates after OLT.

Currently no definite blood tests (biochemical markers) can identify relapses after OLT. Isolated elevations in a liver enzyme called gamma-glutamyl transpeptidase without concomitant elevation of another enzyme, called alkaline phosphatase, may serve as a surrogate marker of relapse. Further research directed at identifying a marker that can indicate abstinence over a period of time would be valuable for monitoring the patients' drinking behavior before and after OLT.

Investigators must further evaluate the outcome of liver transplantation in patients with severe alcoholic hepatitis; currently these patients rarely are considered for an OLT (because they usually do not have enough time to prove sobriety).

Conclusions

OLT currently is the only definitive treatment for liver failure, including ALD. Because of the shortage of donated organs, however, OLT in patients with ALD remains controversial, mainly out of concerns that the transplanted liver could be "wasted" on a patient who eventually relapses to drinking, thereby damaging the transplanted liver. To address this concern, transplant centers generally perform a multidisciplinary screening procedure before the transplant to identify psychosocial predictors of relapse and select suitable ALD patients for OLT. Higher survival rates and lower relapse rates than expected in ALD patients after OLT have encouraged many transplant centers to reevaluate their criteria for these patients. As a result, many transplant centers currently do not require that ALD patients complete a 6-month abstinence period before being placed on a transplant list. Nevertheless, future studies should focus on identifying patients at risk for relapse, so that preventive and therapeutic interventions can be selectively targeted to these patients.

The ethical debate regarding the justification of OLT in patients with ALD continues, although this subject is less controversial than in the past. Further education of the public regarding the outcomes of liver transplantation in ALD patients should help eliminate the stigma and misapprehensions associated with ALD in the context of OLT and could increase organ donation rates.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.