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Case
A 45-year-old male was admitted to the hospital with severe alcoholic hepatitis. After several days of supportive care and medical therapy, the patient continued to show clinical decline. The patient is now admitted to the intensive-care unit with a Maddrey’s Discriminant Function score of 45 and a Model for End-Stage Liver Disease score of 38. He has no other significant medical comorbidities. On rounds, the patient’s wife, who is at the bedside, asks the team whether her husband would be a candidate for liver transplantation.
Should this patient be offered liver transplantation? What medical and psychosocial factors should we consider? What ethical principles should we consider?
Medical considerations
With the advent of direct-acting antivirals (DAAs), there has been a decline in the number of liver transplants performed for hepatitis C virus–related cirrhosis.1 Instead, alcohol-related liver disease (ALD) has become the most common indication for liver transplant in the United States.2 The 6-month abstinence requirement was a widespread practice within the transplant community that would exclude any patients who were actively drinking from being considered for liver transplant. However, data are inconclusive whether the 6-month rule serves as a predictor of future drinking or poor outcomes after liver transplant.3,4 Unfortunately, many patients with severe alcoholic hepatitis will not survive long enough to fulfill the 6-month requirement.5
In 2011, Mathurin and colleagues led the pivotal European trial demonstrating the effectiveness of liver transplant as a rescue option for highly selected patients with severe alcoholic hepatitis.5 The selection criteria included patients with severe alcoholic hepatitis unresponsive to medical therapy, first liver-decompensating event, presence of close supportive family members, absence of severe psychiatric disorders, and agreement by patients to adhere to lifelong total alcohol abstinence. The study showed that the 6-month survival rate of patients who received early liver transplant was 77%, compared with 25% among those who did not. The positive outcomes were subsequently replicated at several centers in the United States, and this led to a wider adoption of early liver transplant for severe alcoholic hepatitis.6-8
Psychosocial considerations
At present, we do not have well-validated consensus selection criteria to identify patients with alcoholic hepatitis most suitable for liver transplant. Each transplant center employs its own set of selection criteria with slight variations from the original European trial which prompted a national expert consensus meeting in Dallas in 2019.9 The consortium published a set of guidelines for centers planning to or already performing alcoholic hepatitis transplants. The proposed criteria to determine liver transplant candidacy are the following: 1) patients presenting for the first time with decompensated liver disease who are nonresponders to medical therapy; 2) assessment by a multidisciplinary psychosocial team including a social worker and an additional specialist; 3) no repeated unsuccessful attempts at addiction rehabilitation; 4) lack of other substance use/dependence; 5) insight with a commitment to sobriety; 6) presence of close supportive family members. The goal was to select candidates with the least likelihood of relapse in the hope of preventing poor outcomes after liver transplant. A study by a Johns Hopkins group comparing patients with severe alcoholic hepatitis who underwent careful psychosocial evaluation versus alcoholic cirrhosis with at least 6 months abstinence found that the survival and alcohol relapse rates were similar between the two groups.7
Ethical considerations
Expanding liver transplant indications to include some patients with severe alcoholic hepatitis will uphold the principle of beneficence given clear evidence of a survival benefit. In addition, graft survival rates were comparable with those of patients who underwent liver transplant for other causes.10 However, in an era of persistent organ shortage, it is important to balance justice or fairness to the patient with utilitarian policies that optimize outcomes for all who are in need of liver transplantation.
Justice
Justice means fair and equal distribution of scarce health resources to patients without bias on account of sex, race, wealth, and the nature of a patient’s disease. Based on the principle of justice, a patient with alcoholic hepatitis should be afforded opportunities for liver transplant equal to patients with other etiologies of liver disease.
Opponents of adoption of liver transplant for alcoholic hepatitis often base their reluctance on the following: patients’ failure to gain control of their alcohol use disorder, fears of alcohol relapse, and ultimately perceptions that these patients may be less deserving, compared with patients with other etiologies of liver disease. But, is this fair to the patient?
Alcohol use disorder, in general, is stigmatized and is considered by some to be a self-inflicted condition. As a medical community, we do not withhold life-saving treatment from patients who had inflicted their own injuries. Nevertheless, the stigma against alcoholism is so entrenched in our society that some fear transplanting a patient who is actively drinking would negatively affect the public’s perception of the transplant community and thus diminish the organ donation rate and harm the common good. Interestingly, a public opinion survey actually showed that the majority of respondents were at least neutral about the idea of transplanting patients with alcoholic hepatitis.11
Utility
Utility means achieving the greatest good for the greatest number of patients. The absolute scarcity of available organs imposes a need for a strict allocation decision. A liver that is used for a patient with severe alcoholic hepatitis is an organ not used for another patient suffering chronic liver disease. It is worth noting that about 20% of patients with severe alcoholic hepatitis might recover without a transplant.5 That means about one out of five liver transplants performed for alcoholic hepatitis may have been done in a patient who would have recovered without a transplant. Does this policy optimize the greatest good for everyone who is on the wait list?
Moss and Siegler argued that it was not the alcoholism that made patients with alcoholic liver disease less deserving of liver transplant, but rather their failure to seek treatment for alcoholism that made their claim for liver transplant weaker, compared with those who developed cirrhosis through no fault of their own.12 This argument is problematic. For example, patients with nonalcoholic steatohepatitis (NASH) are often compared with patients with alcoholic liver disease when it comes to modifiable behaviors that affect their health, whether it is through weight loss or abstinence, respectively. Yet, there is very little argument for lower priority for NASH patients who failed to lose weight. Secondly, alcohol use disorder is a psychosocially complex disease that requires a multidisciplinary treatment approach. Substance abuse rehabilitation is not readily available to most patients and could single out vulnerable patients from lower socioeconomic classes who are at higher risk for developing alcohol use disorder. Imposing a strict abstinence period regardless of a patient’s medical need is punitive and does not treat the underlying disease. Instead of focusing on disease causality, we ought to advocate for medical treatment of the underlying disease.
Conclusions
Liver transplant effectively functions as a zero-sum game. Efforts to save individual patients with severe alcoholic hepatitis can result in trade-offs to other patients on the wait list. Balancing the ethical principles of utility and justice is challenging. A strict 6-month rule, while convenient, does not strike the balance. The decision to transplant a patient with alcoholic hepatitis should be made on a case-by-case basis. As stewards of donor organs, transplant centers have a duty to carefully evaluate a potential candidate based on medical needs and recipient outcome without the influence of bias. We feel that, when considering liver transplant in patients with severe alcoholic hepatitis, the principle of justice or fairness to the patient is the overriding ethical principle. Provided the patient meets medical and psychosocial criteria that available evidence suggests would result in long-term survival post transplantation, we would support listing for liver transplantation.
References
1. Goldberg D et al. Gastroenterology, 2017;152(5):1090-9.e1.
2. Cholankeril G, Ahmed A. Clin Gastroenterol Hepatol. 2018;16(8):1356-8.
3. Neuberger J et al. J Hepatol. 2002;36(1):130-7.
4. DiMartini A, et al. Clin Liver Dis. 2011;15(4):727-51.
5. Mathurin P et al. N Engl J Med, 2011;365(19):1790-800.
6. Im GY et al. Am J Transplant. 2016;16(3):841-9.
7. Lee BP et al. Ann Surg. 2017;265(1):20-9.
8. Lee BP et al. Gastroenterology. 2018. 155(2):422-30.e1.
9. Asrani SK et al. Liver Transpl. 2020;26(1):127-40.
10. Singal AK et al. Transplantation. 2013;95(5):755-60.
11. Stroh G et al. Am J Transplant. 2015;15(6):1598-604.
12. Moss AH, Siegler M. JAMA. 1991;265(10):1295-8.
Dr. Wang is a gastroenterology fellow in the division of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine; Dr. Aronsohn is associate professor in the division of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine.
Case
A 45-year-old male was admitted to the hospital with severe alcoholic hepatitis. After several days of supportive care and medical therapy, the patient continued to show clinical decline. The patient is now admitted to the intensive-care unit with a Maddrey’s Discriminant Function score of 45 and a Model for End-Stage Liver Disease score of 38. He has no other significant medical comorbidities. On rounds, the patient’s wife, who is at the bedside, asks the team whether her husband would be a candidate for liver transplantation.
Should this patient be offered liver transplantation? What medical and psychosocial factors should we consider? What ethical principles should we consider?
Medical considerations
With the advent of direct-acting antivirals (DAAs), there has been a decline in the number of liver transplants performed for hepatitis C virus–related cirrhosis.1 Instead, alcohol-related liver disease (ALD) has become the most common indication for liver transplant in the United States.2 The 6-month abstinence requirement was a widespread practice within the transplant community that would exclude any patients who were actively drinking from being considered for liver transplant. However, data are inconclusive whether the 6-month rule serves as a predictor of future drinking or poor outcomes after liver transplant.3,4 Unfortunately, many patients with severe alcoholic hepatitis will not survive long enough to fulfill the 6-month requirement.5
In 2011, Mathurin and colleagues led the pivotal European trial demonstrating the effectiveness of liver transplant as a rescue option for highly selected patients with severe alcoholic hepatitis.5 The selection criteria included patients with severe alcoholic hepatitis unresponsive to medical therapy, first liver-decompensating event, presence of close supportive family members, absence of severe psychiatric disorders, and agreement by patients to adhere to lifelong total alcohol abstinence. The study showed that the 6-month survival rate of patients who received early liver transplant was 77%, compared with 25% among those who did not. The positive outcomes were subsequently replicated at several centers in the United States, and this led to a wider adoption of early liver transplant for severe alcoholic hepatitis.6-8
Psychosocial considerations
At present, we do not have well-validated consensus selection criteria to identify patients with alcoholic hepatitis most suitable for liver transplant. Each transplant center employs its own set of selection criteria with slight variations from the original European trial which prompted a national expert consensus meeting in Dallas in 2019.9 The consortium published a set of guidelines for centers planning to or already performing alcoholic hepatitis transplants. The proposed criteria to determine liver transplant candidacy are the following: 1) patients presenting for the first time with decompensated liver disease who are nonresponders to medical therapy; 2) assessment by a multidisciplinary psychosocial team including a social worker and an additional specialist; 3) no repeated unsuccessful attempts at addiction rehabilitation; 4) lack of other substance use/dependence; 5) insight with a commitment to sobriety; 6) presence of close supportive family members. The goal was to select candidates with the least likelihood of relapse in the hope of preventing poor outcomes after liver transplant. A study by a Johns Hopkins group comparing patients with severe alcoholic hepatitis who underwent careful psychosocial evaluation versus alcoholic cirrhosis with at least 6 months abstinence found that the survival and alcohol relapse rates were similar between the two groups.7
Ethical considerations
Expanding liver transplant indications to include some patients with severe alcoholic hepatitis will uphold the principle of beneficence given clear evidence of a survival benefit. In addition, graft survival rates were comparable with those of patients who underwent liver transplant for other causes.10 However, in an era of persistent organ shortage, it is important to balance justice or fairness to the patient with utilitarian policies that optimize outcomes for all who are in need of liver transplantation.
Justice
Justice means fair and equal distribution of scarce health resources to patients without bias on account of sex, race, wealth, and the nature of a patient’s disease. Based on the principle of justice, a patient with alcoholic hepatitis should be afforded opportunities for liver transplant equal to patients with other etiologies of liver disease.
Opponents of adoption of liver transplant for alcoholic hepatitis often base their reluctance on the following: patients’ failure to gain control of their alcohol use disorder, fears of alcohol relapse, and ultimately perceptions that these patients may be less deserving, compared with patients with other etiologies of liver disease. But, is this fair to the patient?
Alcohol use disorder, in general, is stigmatized and is considered by some to be a self-inflicted condition. As a medical community, we do not withhold life-saving treatment from patients who had inflicted their own injuries. Nevertheless, the stigma against alcoholism is so entrenched in our society that some fear transplanting a patient who is actively drinking would negatively affect the public’s perception of the transplant community and thus diminish the organ donation rate and harm the common good. Interestingly, a public opinion survey actually showed that the majority of respondents were at least neutral about the idea of transplanting patients with alcoholic hepatitis.11
Utility
Utility means achieving the greatest good for the greatest number of patients. The absolute scarcity of available organs imposes a need for a strict allocation decision. A liver that is used for a patient with severe alcoholic hepatitis is an organ not used for another patient suffering chronic liver disease. It is worth noting that about 20% of patients with severe alcoholic hepatitis might recover without a transplant.5 That means about one out of five liver transplants performed for alcoholic hepatitis may have been done in a patient who would have recovered without a transplant. Does this policy optimize the greatest good for everyone who is on the wait list?
Moss and Siegler argued that it was not the alcoholism that made patients with alcoholic liver disease less deserving of liver transplant, but rather their failure to seek treatment for alcoholism that made their claim for liver transplant weaker, compared with those who developed cirrhosis through no fault of their own.12 This argument is problematic. For example, patients with nonalcoholic steatohepatitis (NASH) are often compared with patients with alcoholic liver disease when it comes to modifiable behaviors that affect their health, whether it is through weight loss or abstinence, respectively. Yet, there is very little argument for lower priority for NASH patients who failed to lose weight. Secondly, alcohol use disorder is a psychosocially complex disease that requires a multidisciplinary treatment approach. Substance abuse rehabilitation is not readily available to most patients and could single out vulnerable patients from lower socioeconomic classes who are at higher risk for developing alcohol use disorder. Imposing a strict abstinence period regardless of a patient’s medical need is punitive and does not treat the underlying disease. Instead of focusing on disease causality, we ought to advocate for medical treatment of the underlying disease.
Conclusions
Liver transplant effectively functions as a zero-sum game. Efforts to save individual patients with severe alcoholic hepatitis can result in trade-offs to other patients on the wait list. Balancing the ethical principles of utility and justice is challenging. A strict 6-month rule, while convenient, does not strike the balance. The decision to transplant a patient with alcoholic hepatitis should be made on a case-by-case basis. As stewards of donor organs, transplant centers have a duty to carefully evaluate a potential candidate based on medical needs and recipient outcome without the influence of bias. We feel that, when considering liver transplant in patients with severe alcoholic hepatitis, the principle of justice or fairness to the patient is the overriding ethical principle. Provided the patient meets medical and psychosocial criteria that available evidence suggests would result in long-term survival post transplantation, we would support listing for liver transplantation.
References
1. Goldberg D et al. Gastroenterology, 2017;152(5):1090-9.e1.
2. Cholankeril G, Ahmed A. Clin Gastroenterol Hepatol. 2018;16(8):1356-8.
3. Neuberger J et al. J Hepatol. 2002;36(1):130-7.
4. DiMartini A, et al. Clin Liver Dis. 2011;15(4):727-51.
5. Mathurin P et al. N Engl J Med, 2011;365(19):1790-800.
6. Im GY et al. Am J Transplant. 2016;16(3):841-9.
7. Lee BP et al. Ann Surg. 2017;265(1):20-9.
8. Lee BP et al. Gastroenterology. 2018. 155(2):422-30.e1.
9. Asrani SK et al. Liver Transpl. 2020;26(1):127-40.
10. Singal AK et al. Transplantation. 2013;95(5):755-60.
11. Stroh G et al. Am J Transplant. 2015;15(6):1598-604.
12. Moss AH, Siegler M. JAMA. 1991;265(10):1295-8.
Dr. Wang is a gastroenterology fellow in the division of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine; Dr. Aronsohn is associate professor in the division of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine.
Case
A 45-year-old male was admitted to the hospital with severe alcoholic hepatitis. After several days of supportive care and medical therapy, the patient continued to show clinical decline. The patient is now admitted to the intensive-care unit with a Maddrey’s Discriminant Function score of 45 and a Model for End-Stage Liver Disease score of 38. He has no other significant medical comorbidities. On rounds, the patient’s wife, who is at the bedside, asks the team whether her husband would be a candidate for liver transplantation.
Should this patient be offered liver transplantation? What medical and psychosocial factors should we consider? What ethical principles should we consider?
Medical considerations
With the advent of direct-acting antivirals (DAAs), there has been a decline in the number of liver transplants performed for hepatitis C virus–related cirrhosis.1 Instead, alcohol-related liver disease (ALD) has become the most common indication for liver transplant in the United States.2 The 6-month abstinence requirement was a widespread practice within the transplant community that would exclude any patients who were actively drinking from being considered for liver transplant. However, data are inconclusive whether the 6-month rule serves as a predictor of future drinking or poor outcomes after liver transplant.3,4 Unfortunately, many patients with severe alcoholic hepatitis will not survive long enough to fulfill the 6-month requirement.5
In 2011, Mathurin and colleagues led the pivotal European trial demonstrating the effectiveness of liver transplant as a rescue option for highly selected patients with severe alcoholic hepatitis.5 The selection criteria included patients with severe alcoholic hepatitis unresponsive to medical therapy, first liver-decompensating event, presence of close supportive family members, absence of severe psychiatric disorders, and agreement by patients to adhere to lifelong total alcohol abstinence. The study showed that the 6-month survival rate of patients who received early liver transplant was 77%, compared with 25% among those who did not. The positive outcomes were subsequently replicated at several centers in the United States, and this led to a wider adoption of early liver transplant for severe alcoholic hepatitis.6-8
Psychosocial considerations
At present, we do not have well-validated consensus selection criteria to identify patients with alcoholic hepatitis most suitable for liver transplant. Each transplant center employs its own set of selection criteria with slight variations from the original European trial which prompted a national expert consensus meeting in Dallas in 2019.9 The consortium published a set of guidelines for centers planning to or already performing alcoholic hepatitis transplants. The proposed criteria to determine liver transplant candidacy are the following: 1) patients presenting for the first time with decompensated liver disease who are nonresponders to medical therapy; 2) assessment by a multidisciplinary psychosocial team including a social worker and an additional specialist; 3) no repeated unsuccessful attempts at addiction rehabilitation; 4) lack of other substance use/dependence; 5) insight with a commitment to sobriety; 6) presence of close supportive family members. The goal was to select candidates with the least likelihood of relapse in the hope of preventing poor outcomes after liver transplant. A study by a Johns Hopkins group comparing patients with severe alcoholic hepatitis who underwent careful psychosocial evaluation versus alcoholic cirrhosis with at least 6 months abstinence found that the survival and alcohol relapse rates were similar between the two groups.7
Ethical considerations
Expanding liver transplant indications to include some patients with severe alcoholic hepatitis will uphold the principle of beneficence given clear evidence of a survival benefit. In addition, graft survival rates were comparable with those of patients who underwent liver transplant for other causes.10 However, in an era of persistent organ shortage, it is important to balance justice or fairness to the patient with utilitarian policies that optimize outcomes for all who are in need of liver transplantation.
Justice
Justice means fair and equal distribution of scarce health resources to patients without bias on account of sex, race, wealth, and the nature of a patient’s disease. Based on the principle of justice, a patient with alcoholic hepatitis should be afforded opportunities for liver transplant equal to patients with other etiologies of liver disease.
Opponents of adoption of liver transplant for alcoholic hepatitis often base their reluctance on the following: patients’ failure to gain control of their alcohol use disorder, fears of alcohol relapse, and ultimately perceptions that these patients may be less deserving, compared with patients with other etiologies of liver disease. But, is this fair to the patient?
Alcohol use disorder, in general, is stigmatized and is considered by some to be a self-inflicted condition. As a medical community, we do not withhold life-saving treatment from patients who had inflicted their own injuries. Nevertheless, the stigma against alcoholism is so entrenched in our society that some fear transplanting a patient who is actively drinking would negatively affect the public’s perception of the transplant community and thus diminish the organ donation rate and harm the common good. Interestingly, a public opinion survey actually showed that the majority of respondents were at least neutral about the idea of transplanting patients with alcoholic hepatitis.11
Utility
Utility means achieving the greatest good for the greatest number of patients. The absolute scarcity of available organs imposes a need for a strict allocation decision. A liver that is used for a patient with severe alcoholic hepatitis is an organ not used for another patient suffering chronic liver disease. It is worth noting that about 20% of patients with severe alcoholic hepatitis might recover without a transplant.5 That means about one out of five liver transplants performed for alcoholic hepatitis may have been done in a patient who would have recovered without a transplant. Does this policy optimize the greatest good for everyone who is on the wait list?
Moss and Siegler argued that it was not the alcoholism that made patients with alcoholic liver disease less deserving of liver transplant, but rather their failure to seek treatment for alcoholism that made their claim for liver transplant weaker, compared with those who developed cirrhosis through no fault of their own.12 This argument is problematic. For example, patients with nonalcoholic steatohepatitis (NASH) are often compared with patients with alcoholic liver disease when it comes to modifiable behaviors that affect their health, whether it is through weight loss or abstinence, respectively. Yet, there is very little argument for lower priority for NASH patients who failed to lose weight. Secondly, alcohol use disorder is a psychosocially complex disease that requires a multidisciplinary treatment approach. Substance abuse rehabilitation is not readily available to most patients and could single out vulnerable patients from lower socioeconomic classes who are at higher risk for developing alcohol use disorder. Imposing a strict abstinence period regardless of a patient’s medical need is punitive and does not treat the underlying disease. Instead of focusing on disease causality, we ought to advocate for medical treatment of the underlying disease.
Conclusions
Liver transplant effectively functions as a zero-sum game. Efforts to save individual patients with severe alcoholic hepatitis can result in trade-offs to other patients on the wait list. Balancing the ethical principles of utility and justice is challenging. A strict 6-month rule, while convenient, does not strike the balance. The decision to transplant a patient with alcoholic hepatitis should be made on a case-by-case basis. As stewards of donor organs, transplant centers have a duty to carefully evaluate a potential candidate based on medical needs and recipient outcome without the influence of bias. We feel that, when considering liver transplant in patients with severe alcoholic hepatitis, the principle of justice or fairness to the patient is the overriding ethical principle. Provided the patient meets medical and psychosocial criteria that available evidence suggests would result in long-term survival post transplantation, we would support listing for liver transplantation.
References
1. Goldberg D et al. Gastroenterology, 2017;152(5):1090-9.e1.
2. Cholankeril G, Ahmed A. Clin Gastroenterol Hepatol. 2018;16(8):1356-8.
3. Neuberger J et al. J Hepatol. 2002;36(1):130-7.
4. DiMartini A, et al. Clin Liver Dis. 2011;15(4):727-51.
5. Mathurin P et al. N Engl J Med, 2011;365(19):1790-800.
6. Im GY et al. Am J Transplant. 2016;16(3):841-9.
7. Lee BP et al. Ann Surg. 2017;265(1):20-9.
8. Lee BP et al. Gastroenterology. 2018. 155(2):422-30.e1.
9. Asrani SK et al. Liver Transpl. 2020;26(1):127-40.
10. Singal AK et al. Transplantation. 2013;95(5):755-60.
11. Stroh G et al. Am J Transplant. 2015;15(6):1598-604.
12. Moss AH, Siegler M. JAMA. 1991;265(10):1295-8.
Dr. Wang is a gastroenterology fellow in the division of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine; Dr. Aronsohn is associate professor in the division of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine.