Liver transplantation in alcohol-associated liver disease: ensuring equity through new processes.

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients.

What Should I Do?

: The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.

A Mixed-Methods Approach to Understanding Variation in Social Support Requirements and Implications for Access to Transplantation in the United States.

Social support is a key component of transplantation evaluation in the United States. Social support definitions and evaluation procedures require examination to achieve clear, consistent implementation. We surveyed psychosocial clinicians from the Society for Transplant Social Workers and American Society of Transplant Surgeons about their definitions and evaluation procedures for using social support to determine transplant eligibility. Bivariate statistical analysis was used for quantitative data and content analysis for qualitative data. Among 276 psychosocial clinicians (50.2% response rate), 92% had ruled out patients from transplantation due to inadequate support. Social support definitions varied significantly: 10% of respondents indicated their center lacked a definition. Key domains of social support included informational, emotional, instrumental, motivational, paid support, and the patient's importance to others. Almost half of clinicians (47%) rarely or never requested second opinions when excluding patients due to social support. Confidence and perceived clarity and consistency in center guidelines were significantly associated with informing patients when support contributed to negative wait-listing decisions (P = .001). Clinicians who excluded fewer patients because of social support offered significantly more supportive health care (P = .02). Clearer definitions and more supportive care may reduce the number of patients excluded from transplant candidacy due to inadequate social support.

Excluding patients from transplant due to social support: Results from a national survey of transplant providers.

Social support is used to determine transplant eligibility despite lack of an evidence base and vague regulatory guidance. It is unknown how many patients are disqualified from transplantation due to inadequate support, and whether providers feel confident using these subjective criteria to determine eligibility. Transplant providers (n = 551) from 202 centers estimated that, on average, 9.6% (standard deviation = 9.4) of patients evaluated in the prior year were excluded due to inadequate support. This varied significantly by United Network for Organ Sharing region (7.6%-12.2%), and by center (21.7% among top quartile). Significantly more providers used social support in listing decisions than believed it ought to be used (86.3% vs 67.6%). Nearly 25% believed that using social support in listing determinations was unfair or were unsure; 67.3% felt it disproportionately impacted patients of low socioeconomic status. Overall, 42.4% were only somewhat or not at all confident using social support to determine transplant suitability. Compared to surgical/medical transplant providers, psychosocial providers had 2.13 greater odds of supporting the criteria (P = .03). Furthermore, 69.2% supported revised guidelines for use of social support in listing decisions. Social support criteria should be reconsidered in light of the limited evidence, potential for disparities, practice variation, low provider confidence, and desire for revised guidelines.

How important is social support in determining patients' suitability for transplantation? Results from a National Survey of Transplant Clinicians.

BACKGROUND: National guidelines require programmes use subjective assessments of social support when determining transplant suitability, despite limited evidence linking it to outcomes. We examined how transplant providers weigh the importance of social support for kidney transplantation compared with other factors, and variation by clinical role and personal beliefs. METHODS: The National survey of the American Society of Transplant Surgeons and the Society of Transplant Social Work in 2016. Using a discrete choice approach, respondents compared two hypothetical patient profiles and selected one for transplantation. Conditional logistic regression estimated the relative importance of each factor; results were stratified by clinical role (psychosocial vs medical/surgical providers) and beliefs (outcomes vs equity). RESULTS: Five hundred and eighy-four transplant providers completed the survey. Social support was the second most influential factor among transplant providers. Providers were most likely to choose a candidate who had social support (OR=1.68, 95% CI 1.50 to 1.86), always adhered to a medical regimen (OR=1.64, 95% CI 1.46 to 1.88), and had a 15 years life expectancy with transplant (OR=1.61, 95% CI 1.42 to 1.85). Psychosocial providers were more influenced by adherence and quality of life compared with medical/surgical providers, who were more influenced by candidates' life expectancy with transplant (p<0.05). For providers concerned with avoiding organ waste, social support was the most influential factor, while it was the least influential for clinicians concerned with fairness (p<0.05). CONCLUSIONS: Social support is highly influential in listing decisions and may exacerbate transplant disparities. Providers' beliefs and reliance on social support in determining suitability vary considerably, raising concerns about transparency and justice.

Directed solutions to address differences in access to liver transplantation.

The United Network for Organ Sharing recently altered current liver allocation with the goal of decreasing Model for End-Stage Liver Disease (MELD) variance at transplant. Concerns over these and further planned revisions to policy include predicted decrease in total transplants, increased flying and logistical complexity, adverse impact on areas with poor quality health care, and minimal effect on high MELD donor service areas. To address these issues, we describe general approaches to equalize critical transplant metrics among regions and determine how they alter MELD variance at transplant and organ supply to underserved communities. We show an allocation system that increases minimum MELD for local allocation or preferentially directs organs into areas of need decreases MELD variance. Both models have minimal adverse effects on flying and total transplants, and do not disproportionately disadvantage already underserved communities. When combined together, these approaches decrease MELD variance by 28%, more than the recently adopted proposal. These models can be adapted for any measure of variance, can be combined with other proposals, and can be configured to automatically adjust to changes in disease incidence as is occurring with hepatitis C and nonalcoholic fatty liver disease.

Are geographic differences in transplantation inherently wrong?

PURPOSE OF REVIEW: Geographic variation in liver transplantation has been the subject of extensive scrutiny, reflecting concerns that location is unfairly determinative for people needing organ transplantation. Drawing upon a number of established ethical approaches, we examine whether geographic differences in access to livers are inherently unethical. RECENT FINDINGS: We posit that the ethical imperative for redistribution largely hinges upon the belief that access to organs systematically disadvantages certain identifiable groups of patients over others. Yet, our data suggest that regions likely to be net-contributors may suffer from less access to transplantation and other health services, fewer social protections and greater burden of liver disease. Drawing upon a number of ethical approaches, including strict egalitarianism, utilitarianism, Maximin, Reciprocity, Sen's Impartial Spectator and a health equity framework, we demonstrate that the current proposal has significant weaknesses, and may not achieve its goals of improving equity and efficiency. SUMMARY: Formulating effective policies and programs to ameliorate health inequalities requires an understanding of the interrelated causes of mortality disparities and specific interventions to mitigate these causes. Although our analysis does not indicate how ethically distribute livers, but it suggests that this be done with consideration for population-based health measures.

Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls.

OBJECTIVES: To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients. DESIGN: Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls. METHODS: We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models. RESULTS: There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis. CONCLUSION: Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.

Ischemia-reperfusion injury in kidney transplantation.

Ischemia-reperfusion injury to the kidney is a complex pathophysiological process that has importance during transplantation as it affects graft function and survival. It starts with the physiological changes associated with the death of the donor, including the direct effects of hypoxia and metabolic stress. The injury continues through the organ procurement and preservation procedures. Upon reperfusion, the organ is then further damaged by a reactive inflammatory process which had been primed during the earlier injuries. Clinically, the damage from microvascular dysfunction and cytotoxic agents contributed by the immunologic response results in impaired graft function or graft loss. Recent advances in understanding the specific pathways involved in this injury have helped identify novel therapies. Nevertheless, ischemia-reperfusion injury continues to be a daunting problem even as these treatment strategies are being evaluated for clinical use.

The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of relapse to any alcohol use after liver transplant.

CONTEXT: Alcohol relapse after liver transplant heightens concern about recurrent disease, nonadherence to the immunosuppression regimen, and death. OBJECTIVES: To develop a scoring system to stratify risk of alcohol relapse after liver transplant. DESIGN: Retrospective medical record review. SETTING AND PARTICIPANTS: All adult liver transplants performed from May 2002 to February 2011 at a single center in the United States. MAIN OUTCOME MEASURE: The incidence of return to any alcohol consumption after liver transplant. RESULTS: Thirty-four percent (40/118) of patients with a history of alcohol abuse/dependency relapsed to use of any alcohol after liver transplant. Nine of 25 hypothesized risk factors were predictive of alcohol relapse after liver transplant: absence of hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver disease diagnosis, low motivation for alcohol treatment, poor stress management skills, no rehabilitation relationship, limited social support, lack of nonmedical behavioral consequences, and continued engagement in social activities with alcohol present. Each independent predictor was assigned an Alcohol Relapse Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1 of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly higher rates of alcohol relapse and were more likely to return to pretransplant levels of drinking. CONCLUSION: Alcohol relapse rates are moderately high after liver transplant. The ARRA is a valid and practical tool for identifying pretransplant patients with alcohol abuse or dependency at elevated risk of any alcohol use after liver transplant.

Patient-reported immunosuppression nonadherence 6 to 24 months after liver transplant: association with pretransplant psychosocial factors and perceptions of health status change.

CONTEXT: Knowing the prevalence and risk factors of immunosuppression nonadherence after liver transplant may help guide intervention development. OBJECTIVE: To examine whether sociodemographic and psychosocial variables before liver transplant are predictive of nonadherence after liver transplant. DESIGN: Structured telephone interviews were used to collect self-report immunosuppression adherence and health status information. Medical record reviews were then completed to retrospectively examine the relationship between immunosuppression adherence and pretransplant variables, including sociodemographic and medical characteristics and the presence or absence of 6 hypothesized psychosocial risk factors. SETTING AND PARTICIPANTS: A nonprobability sample of 236 adults 6 to 24 months after liver transplant at 2 centers completed structured telephone interviews. MAIN OUTCOME MEASURE: Immunosuppressant medication nonadherence, categorized as missed-dose and altered-dose "adherent" or "nonadherent" during the past 6 months; immunosuppression medication holidays. RESULTS: Eighty-two patients (35%) were missed-dose nonadherent and 34 patients (14%) were altered-dose nonadherent. Seventy-one patients (30%) reported 1 or more 24-hour immunosuppression holidays in the past 6 months. Missed-dose nonadherence was predicted by male sex (odds ratio, 2.46; P= .01), longer time since liver transplant (odds ratio, 1.08; P= .01), pretransplant mood disorder (odds ratio, 2.52; P=.004), and pretransplant social support instability (odds ratio, 2.25; P=.03). Altered-dose nonadherence was predicted by pretransplant mood disorder (odds ratio, 2.15; P= .04) and pretransplant social support instability (odds ratio, 1.89; P= .03). CONCLUSION: Rates of immunosuppressant nonadherence and drug holidays in the first 2 years after liver transplant are unacceptably high. Pretransplant mood disorder and social support instability increase the risk of nonadherence, and interventions should target these modifiable risk factors.

Renal transplantation in the setting of early steroid withdrawal: a comparison of rabbit antithymocyte globulin induction dosing in two eras.

BACKGROUND: Modern immunosuppression and rabbit antithymocyte globulin (rATG) have facilitated the success of early steroid withdrawal (ESW) protocols. Little data exist on optimal rATG dosing in ESW protocols. METHODS: Rejection at 12 months in era 1 (four doses of rATG, 1.25 mg/kg) vs. era 2 (three doses of rATG, 1.25 mg/kg) was the primary endpoint. Secondary endpoints included patient and graft survival, renal function and infectious complications. Factors associated with rejection at 1 year were identified. RESULTS: 199 patients received rATG induction and ESW: 102 in era 1 and 97 in era 2. Compared to era 1, era 2 was not associated with worse outcomes, including rejection, renal function, infection or graft survival. Rejection at 1 year and uncensored graft survival differed between the dosing groups. Rejection rates were significantly higher in the <4 mg/kg group compared to the 4-5.9-mg/kg and the ≥6-mg/kg groups, whereas uncensored graft survival was the lowest in the ≥6-mg/kg group. Factors associated with rejection at 12 months included: rATG dose received of 4-5.9 versus <4 mg/kg (OR 0.20, 95% CI 0.036-0.85, p = 0.026); recipient age (per year, OR 0.94, 95% CI 0.89-1.0, p = 0.038); panel reactive antibody 10-79.9 versus <10% (OR 5.4, 95% CI 1.2-25, p = 0.030) and rATG dose held (OR 4.0, 95% CI 1.0-15, p = 0.049). CONCLUSIONS: A comparison of rATG dosing based on era did not result in a significant difference in rejection, renal function, infection or graft survival. However, when evaluating the study population based on actual dose received there were notable differences in both rejection rates and uncensored graft survival.