American Journal of Transplantation 2015; 15: 1598–1604 Wiley Periodicals Inc.
C
Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13176
Early Liver Transplantation for Patients With Acute Alcoholic Hepatitis: Public Views and the Effects on Organ Donation G. Stroh1, T. Rosell2, F. Dong3 and J. Forster4,*
Introduction
1
End-stage liver disease (ESLD) due to alcohol abuse has been a common indication for liver transplantation since the therapy first became widely available (1). Such patients are usually required to undergo 6 months of abstinence and counseling prior to being listed for a liver transplant. Despite meeting that requirement, the risk of posttransplant recidivism remains an ongoing problem for transplant teams caring for such patients. There is little consensus on the true posttransplant recidivism rate, which has been reported to be as low as 10% and as high as 95%, depending on the length of the study and variations in patient management, among other factors (2,3). The average rate across 30 studies was approximately 27% for any given period of time (4). The high rate of recidivism is concerning and may explain the generally negative perception of liver transplantation for alcoholics by the public. A study has shown that the public views organ allocation to patients with alcohol-induced disease less favorably than those with inherited or acquired illnesses less directly related to behavior (5). These findings are supported by studies done in France and the United Kingdom (6,7).
University of Kansas School of Medicine, Kansas City, KS Department of History and Philosophy of Medicine, University of Kansas Medical Center, Kansas City, KS 3 Department of Preventive Medicine and Public Health, University of Kansas School of Medicine-Wichita, Wichita, KS 4 Saint Luke’s Transplant Specialists, Saint Luke’s Health System, Kansas City, MO Corresponding author: Jameson Forster, [email protected] Correction made after online publication February 23, 2015: corresponding author has been changed. 2
Patients with severe acute alcoholic hepatitis may not survive to fulfill the standard 6 months of abstinence and counseling prior to transplantation. A prospective study demonstrated that early liver transplantation in such patients improved 2 year survival from 23% to 71% and only 3 of 26 patients returned to drinking after 1140 days; graft function was unaffected. Nonetheless, this treatment protocol may raise public concerns and affect organ donation rates. A total of 503 participants took a survey made available at an online crowdsourcing marketplace. The survey measured attitudes on liver transplantation generally and early transplantation for this patient population, in addition to measuring responses to nine vignettes describing fictional candidates. The majority of respondents (81.5%, n ¼ 410) was at least neutral toward early transplantation for these patients; only a minority (26.3%) indicated that transplantation in any vignette would make them hesitant to donate their organs. Middle-aged patients with good social support and financial stability were viewed most favorably (p < 0.001). Age was considered the most important selection factor and financial stability the least important factor (each p < 0.001). Results indicate early transplantation for carefully selected patients with acute alcoholic hepatitis may not be as controversial to the public as previously thought. Abbreviations: AAH, acute alcoholic hepatitis; eLT, early liver transplantation; ESLD, end stage liver disease Received 15 July 2014, revised 07 December 2014 and accepted for publication 21 December 2014
1598
A sub-set of patients who abuse alcohol may develop severe acute alcoholic hepatitis (AAH) defined by a Maddrey Discriminant Function (DF) >32, which indicates the need to initiate pharmacologic therapy. For patients who do not respond to this treatment modality, clinicians can use the Lille Model to predict which patients have a high 6-month mortality risk. A Lille score >0.45 has been shown to be the optimal method to make this prediction when compared to the MELD, Maddrey Discriminant Function, Glasgow Alcoholic Hepatitis, and Child-Pugh scoring systems (8,9). Studies have shown these patients with refractive AAH have an estimated 6-month mortality rate of 75% (9). Liver transplantation would be an appropriate therapy for these patients, but they would probably not survive if required to undergo the standard 6-month period of abstinence and counseling prior to transplantation (10). Any program that treats patients having severe, refractory AAH with liver transplantation would have to operate prior to the patients demonstrating any significant period of abstinence or undergoing adequate counseling (which we
Early Transplantation for Alcoholic Hepatitis
call early liver transplantation [eLT]). Such a protocol could be highly controversial and might evoke a negative reaction from healthcare professionals and the general public, leading to a lack of support for and anger towards that program; potentially resulting in decreased organ donation rates. Nonetheless, the urgency with which treatment needs to be administered, along with recent challenges to the absoluteness of the 6-month rule, has resulted in a call to perform eLT for patients with refractive AAH. A recent study by Mathurin et al. found that eLT improved 2 year survival in such patients from 23% to 71% when compared to traditional treatments. Importantly, only 3 of 26 patients returned to drinking after 1140 days, and graft-function was not affected in any of those cases (11). Although this group had successful results, eLT remains potentially divisive in light of ongoing organ shortages and the generally higher risk of recidivism in patients without pre-transplantation abstinence and counseling (12,13). This study evaluates the concerns of negative public reactions and the potential decrease in organ donations in response to performing eLT in patients with refractive AAH.
Methods Survey distribution An online survey was created and distributed using Amazon Web Service’s Mechanical Turk (Amazon.com, Inc. Seattle, WA), which is a well-known crowdsourcing marketplace used to distribute surveys online and has one of the largest member pools on the internet. It is used in behavioral research to gain access to large, diverse populations of people, making it an attractive tool for researchers (14). Additionally, the interface is appealing to survey responders because it allows them to receive a small payment in exchange for their time (e.g. $1.00).
Survey availability The survey was made available only to individuals who met three criteria: currently living in the United States, completion of at least 100 previous surveys/tasks, and an approval rating of at least 95%. This is to say that at least 95% of the workers’ prior completed tasks were not rejected. Additionally, incomplete surveys were not accepted by the website and data from any such surveys were not available to the authors.
Survey content The survey began with introductory information on the topic of liver transplantation, on eLT in patients with refractive AAH, and on the controversial aspects of this treatment algorithm (to view the survey, please see the supplemental content). Demographic information such as gender, age, and race/ethnicity was requested, as well as any prior experiences or affiliation with transplantation. The latter question included the following options: no prior involvement with transplantation; family member of organ donor(s); family member of organ recipient(s); organ donor; healthcare professional (not physician) not involved with transplantation; nurse involved with transplantation; physician not involved with transplantation; or physician involved with transplantation.
American Journal of Transplantation 2015; 15: 1598–1604
Respondents were asked if they thought patients should be eligible to receive liver transplants for ESLD secondary to alcohol abuse. They were also asked about plans to donate their own organs and, if they did plan to donate, what actions, if any, they had taken to indicate their intent to donate (indicated on driver’s license; placed name on donor registry; talked to family about wishes to donate; indicated on advance directive; and/or other). A chief component of the survey was nine case vignettes that described fictional patients with refractive AAH in need of eLT, each of whom was estimated to live less than 6 months. The vignettes gave a brief personal history of each fictional patient, the events that led up to the development of AAH, and information regarding their level of social support and financial stability. None of the fictional patients were described as having alcoholism or indicated to have prior medical complications from alcohol abuse. The responders were asked to rate on a 1–10 scale how they would feel if that patient underwent early liver transplantation (10 ¼ very pleased; 7–8 ¼ pleased; 5 ¼ neutral; 3 ¼ upset; 1 ¼ very upset). Respondents were then asked to rate the importance of age, social support, and financial stability as selection factors when considering patients with AAH for eLT. This question was posed independently of case vignettes and used a scale from 1–10 (10 ¼ very important; 7–8 ¼ more important than other factors; 5 ¼ same importance as any other factor; 3 ¼ less important than other factors; 1 ¼ not important). Finally, respondents were asked what they would think if a nearby transplant program began performing eLT for those with refractive AAH (1–5 scale; 5 ¼ strongly agree, 4 ¼ agree, 3 ¼ neutral, 2 ¼ disagree, or 1 ¼ strongly disagree). Those surveyed were also asked to indicate whether eLT performed in any of the fictional patients would make them hesitant to donate their organs, and, if so, which case(s). An open-ended follow-up question provided respondents the opportunity to express the reasons for their hesitancy to donate their organs if eLT were performed in any of the cases presented.
Data validation To protect against random answers from participants or software posing as a participant, a question was embedded into the survey and gave specific instructions to select a particular answer. If this answer was not selected, the survey data was not used and the participant was not paid. This is recommended when using this method of data collection to protect data validity from potential corruption by random responses (14).
Statistical analysis Statistical analyses were done on SPSS 20 (IBM, Armonk, NY). Descriptive statistics were presented as means and standard deviations for continuous variables, and frequencies and proportions for categorical variables. Oneway analysis of variance (ANOVA) was conducted to identify any differences in age among opinions of eLT implementation (agree þ strongly agree, neutral, and disagree þ strongly disagree) and among individual case vignettes. Chi-square analysis was conducted to identify demographic factors associated with opinions of eLT. Qualitative analysis was conducted using Excel to identify themes among reasons accounting for their hesitancy to donate organs if eLT were implemented in one of the fictional cases. All statistical analyses were two-sided. A p-value
C
Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13176
Early Liver Transplantation for Patients With Acute Alcoholic Hepatitis: Public Views and the Effects on Organ Donation G. Stroh1, T. Rosell2, F. Dong3 and J. Forster4,*
Introduction
1
End-stage liver disease (ESLD) due to alcohol abuse has been a common indication for liver transplantation since the therapy first became widely available (1). Such patients are usually required to undergo 6 months of abstinence and counseling prior to being listed for a liver transplant. Despite meeting that requirement, the risk of posttransplant recidivism remains an ongoing problem for transplant teams caring for such patients. There is little consensus on the true posttransplant recidivism rate, which has been reported to be as low as 10% and as high as 95%, depending on the length of the study and variations in patient management, among other factors (2,3). The average rate across 30 studies was approximately 27% for any given period of time (4). The high rate of recidivism is concerning and may explain the generally negative perception of liver transplantation for alcoholics by the public. A study has shown that the public views organ allocation to patients with alcohol-induced disease less favorably than those with inherited or acquired illnesses less directly related to behavior (5). These findings are supported by studies done in France and the United Kingdom (6,7).
University of Kansas School of Medicine, Kansas City, KS Department of History and Philosophy of Medicine, University of Kansas Medical Center, Kansas City, KS 3 Department of Preventive Medicine and Public Health, University of Kansas School of Medicine-Wichita, Wichita, KS 4 Saint Luke’s Transplant Specialists, Saint Luke’s Health System, Kansas City, MO Corresponding author: Jameson Forster, [email protected] Correction made after online publication February 23, 2015: corresponding author has been changed. 2
Patients with severe acute alcoholic hepatitis may not survive to fulfill the standard 6 months of abstinence and counseling prior to transplantation. A prospective study demonstrated that early liver transplantation in such patients improved 2 year survival from 23% to 71% and only 3 of 26 patients returned to drinking after 1140 days; graft function was unaffected. Nonetheless, this treatment protocol may raise public concerns and affect organ donation rates. A total of 503 participants took a survey made available at an online crowdsourcing marketplace. The survey measured attitudes on liver transplantation generally and early transplantation for this patient population, in addition to measuring responses to nine vignettes describing fictional candidates. The majority of respondents (81.5%, n ¼ 410) was at least neutral toward early transplantation for these patients; only a minority (26.3%) indicated that transplantation in any vignette would make them hesitant to donate their organs. Middle-aged patients with good social support and financial stability were viewed most favorably (p < 0.001). Age was considered the most important selection factor and financial stability the least important factor (each p < 0.001). Results indicate early transplantation for carefully selected patients with acute alcoholic hepatitis may not be as controversial to the public as previously thought. Abbreviations: AAH, acute alcoholic hepatitis; eLT, early liver transplantation; ESLD, end stage liver disease Received 15 July 2014, revised 07 December 2014 and accepted for publication 21 December 2014
1598
A sub-set of patients who abuse alcohol may develop severe acute alcoholic hepatitis (AAH) defined by a Maddrey Discriminant Function (DF) >32, which indicates the need to initiate pharmacologic therapy. For patients who do not respond to this treatment modality, clinicians can use the Lille Model to predict which patients have a high 6-month mortality risk. A Lille score >0.45 has been shown to be the optimal method to make this prediction when compared to the MELD, Maddrey Discriminant Function, Glasgow Alcoholic Hepatitis, and Child-Pugh scoring systems (8,9). Studies have shown these patients with refractive AAH have an estimated 6-month mortality rate of 75% (9). Liver transplantation would be an appropriate therapy for these patients, but they would probably not survive if required to undergo the standard 6-month period of abstinence and counseling prior to transplantation (10). Any program that treats patients having severe, refractory AAH with liver transplantation would have to operate prior to the patients demonstrating any significant period of abstinence or undergoing adequate counseling (which we
Early Transplantation for Alcoholic Hepatitis
call early liver transplantation [eLT]). Such a protocol could be highly controversial and might evoke a negative reaction from healthcare professionals and the general public, leading to a lack of support for and anger towards that program; potentially resulting in decreased organ donation rates. Nonetheless, the urgency with which treatment needs to be administered, along with recent challenges to the absoluteness of the 6-month rule, has resulted in a call to perform eLT for patients with refractive AAH. A recent study by Mathurin et al. found that eLT improved 2 year survival in such patients from 23% to 71% when compared to traditional treatments. Importantly, only 3 of 26 patients returned to drinking after 1140 days, and graft-function was not affected in any of those cases (11). Although this group had successful results, eLT remains potentially divisive in light of ongoing organ shortages and the generally higher risk of recidivism in patients without pre-transplantation abstinence and counseling (12,13). This study evaluates the concerns of negative public reactions and the potential decrease in organ donations in response to performing eLT in patients with refractive AAH.
Methods Survey distribution An online survey was created and distributed using Amazon Web Service’s Mechanical Turk (Amazon.com, Inc. Seattle, WA), which is a well-known crowdsourcing marketplace used to distribute surveys online and has one of the largest member pools on the internet. It is used in behavioral research to gain access to large, diverse populations of people, making it an attractive tool for researchers (14). Additionally, the interface is appealing to survey responders because it allows them to receive a small payment in exchange for their time (e.g. $1.00).
Survey availability The survey was made available only to individuals who met three criteria: currently living in the United States, completion of at least 100 previous surveys/tasks, and an approval rating of at least 95%. This is to say that at least 95% of the workers’ prior completed tasks were not rejected. Additionally, incomplete surveys were not accepted by the website and data from any such surveys were not available to the authors.
Survey content The survey began with introductory information on the topic of liver transplantation, on eLT in patients with refractive AAH, and on the controversial aspects of this treatment algorithm (to view the survey, please see the supplemental content). Demographic information such as gender, age, and race/ethnicity was requested, as well as any prior experiences or affiliation with transplantation. The latter question included the following options: no prior involvement with transplantation; family member of organ donor(s); family member of organ recipient(s); organ donor; healthcare professional (not physician) not involved with transplantation; nurse involved with transplantation; physician not involved with transplantation; or physician involved with transplantation.
American Journal of Transplantation 2015; 15: 1598–1604
Respondents were asked if they thought patients should be eligible to receive liver transplants for ESLD secondary to alcohol abuse. They were also asked about plans to donate their own organs and, if they did plan to donate, what actions, if any, they had taken to indicate their intent to donate (indicated on driver’s license; placed name on donor registry; talked to family about wishes to donate; indicated on advance directive; and/or other). A chief component of the survey was nine case vignettes that described fictional patients with refractive AAH in need of eLT, each of whom was estimated to live less than 6 months. The vignettes gave a brief personal history of each fictional patient, the events that led up to the development of AAH, and information regarding their level of social support and financial stability. None of the fictional patients were described as having alcoholism or indicated to have prior medical complications from alcohol abuse. The responders were asked to rate on a 1–10 scale how they would feel if that patient underwent early liver transplantation (10 ¼ very pleased; 7–8 ¼ pleased; 5 ¼ neutral; 3 ¼ upset; 1 ¼ very upset). Respondents were then asked to rate the importance of age, social support, and financial stability as selection factors when considering patients with AAH for eLT. This question was posed independently of case vignettes and used a scale from 1–10 (10 ¼ very important; 7–8 ¼ more important than other factors; 5 ¼ same importance as any other factor; 3 ¼ less important than other factors; 1 ¼ not important). Finally, respondents were asked what they would think if a nearby transplant program began performing eLT for those with refractive AAH (1–5 scale; 5 ¼ strongly agree, 4 ¼ agree, 3 ¼ neutral, 2 ¼ disagree, or 1 ¼ strongly disagree). Those surveyed were also asked to indicate whether eLT performed in any of the fictional patients would make them hesitant to donate their organs, and, if so, which case(s). An open-ended follow-up question provided respondents the opportunity to express the reasons for their hesitancy to donate their organs if eLT were performed in any of the cases presented.
Data validation To protect against random answers from participants or software posing as a participant, a question was embedded into the survey and gave specific instructions to select a particular answer. If this answer was not selected, the survey data was not used and the participant was not paid. This is recommended when using this method of data collection to protect data validity from potential corruption by random responses (14).
Statistical analysis Statistical analyses were done on SPSS 20 (IBM, Armonk, NY). Descriptive statistics were presented as means and standard deviations for continuous variables, and frequencies and proportions for categorical variables. Oneway analysis of variance (ANOVA) was conducted to identify any differences in age among opinions of eLT implementation (agree þ strongly agree, neutral, and disagree þ strongly disagree) and among individual case vignettes. Chi-square analysis was conducted to identify demographic factors associated with opinions of eLT. Qualitative analysis was conducted using Excel to identify themes among reasons accounting for their hesitancy to donate organs if eLT were implemented in one of the fictional cases. All statistical analyses were two-sided. A p-value
