Treatment of Alcohol Use Disorder: Behavioral and Pharmacologic Therapies.

The prevalence of alcohol use disorder (AUD) has significantly increased over the last decade, leading to an increase in alcohol-associated liver disease (ALD) rates worldwide. Despite this prominence, AUD in ALD remains undertreated and carries significant implications in the progression to end-stage ALD and increased mortality. In efforts to bridge this gap, interprofessional and integrated AUD treatment is necessary for patients with ALD to ensure early detection and an appropriately targeted level of care. Although pharmacotherapy, psychotherapy, and psychosocial interventions independently play a role in treating AUD, a combination of these evidence-based modalities often results in lasting change.

Psychosocial Evaluation of Living Kidney Donors: A Survey of Current Practices in the United States.

BACKGROUND: Best practices in psychosocial evaluation and care of living donor candidates and donors are not well established. METHODS: We surveyed 195 living kidney donor (LKD) transplant centers in United States from October 2021 to April 2022 querying (1) composition of psychosocial teams, (2) evaluation processes including clinical tools and domains assessed, (3) selection criteria, and (4) psychosocial follow-up post-donation. RESULTS: We received 161 responses from 104 programs, representing 53% of active LKD programs and 67% of LKD transplant volume in 2019. Most respondents (63%) were social workers/independent living donor advocates. Over 90% of respondents indicated donor candidates with known mental health or substance use disorders were initially evaluated by the psychosocial team. Validated psychometric or transplant-specific tools were rarely utilized but domains assessed were consistent. Active suicidality, self-harm, and psychosis were considered absolute contraindications in >90% of programs. Active depression was absolute contraindication in 50% of programs; active anxiety disorder was excluded 27%. Conditions not contraindicated to donation include those in remission: anxiety (56%), depression (53%), and posttraumatic stress disorder (41%). There was acceptance of donor candidates using alcohol, tobacco, or cannabis recreationally, but not if pattern met criteria for active use disorder. Seventy-one percent of programs conducted post-donation psychosocial assessment and use local resources to support donors. CONCLUSIONS: There was variation in acceptance of donor candidates with mental health or substance use disorders. Although most programs conducted psychosocial screening post-donation, support is not standardized and unclear if adequate. Future studies are needed for consensus building among transplant centers to form guidelines for donor evaluation, acceptance, and support.

Liver transplantation for alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide, and a leading indication for liver transplantation (LT) in many countries, including the United States. However, LT for ALD is a complex and evolving field with ethical, social, and medical challenges. Thus, it requires a multidisciplinary approach and individualized decision-making. Short-term and long-term patient and graft survival of patients undergoing LT for ALD are comparable to other indications, but there is a continued need to develop better tools to identify patients who may benefit from LT, improve the pretransplant and posttransplant management of ALD, and evaluate the impact of LT for ALD on the organ donation and transplantation systems. In this review, we summarize the current evidence on LT for ALD, from alcohol-associated hepatitis to decompensated alcohol-associated cirrhosis. We discuss the indications, criteria, outcomes, and controversies of LT for these conditions and highlight the knowledge gaps and research priorities in this field.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Critical misconceptions and knowledge gaps regarding alcohol cessation and risk of relapse in alcohol-related liver disease patients: A qualitative mental models study.

INTRODUCTION: Despite the mortality benefits of alcohol cessation and alcohol treatment, few patients with alcohol-related liver disease (ALD) get such treatment. To understand reasons for low treatment rates, we performed a qualitative mental models study to explore how ALD patients understand factors influencing alcohol cessation, relapse and their liver health. METHODS: Using a mental models framework, we interviewed experts in alcohol use disorder (AUD) and ALD to determine factors influencing alcohol cessation, risk of relapse and liver health. An expert influence diagram was constructed and used to develop a patient interview guide. We recruited participants with ALD enrolled in hepatology or transplant clinics at a single tertiary-care center. We conducted interviews either face-to-face or by phone, per participant preference. We transcribed all interviews verbatim and analyzed them using combined deductive coding schema based on both the interview guide and emergent coding. RESULTS: 25 (10 women, 15 men) participants with a mean age of 57 years completed interviews. 68 % had decompensated cirrhosis. Major omissions included gender (as a factor in alcohol use or liver disease) and the influence of benzodiazepines/opioids on relapse. Misconceptions were common, in particular the idea that the absence of urges to drink meant participants were safe from relapse. Conceptual differences from the expert model emerged as well. Participants tended to view the self as primary and the only thing that could influence relapse in many cases, resulting in a linear mental model with few nodes influencing alcohol cessation. Participants' risky drinking signals (i.e., elevated liver enzymes) differed from known definitions of hazardous or high-risk drinking, which largely emphasize dose of alcohol consumed irrespective of consequences. Finally, participants sometimes viewed stopping on one's own as the primary means of stopping alcohol use, not recognizing the many other nodes in the influence diagram impacting ability to stop alcohol. CONCLUSION: Patients with ALD had critical misconceptions, omissions, and conceptual reorganizations in their mental models of the ability to stop alcohol use. Attention to these differences may allow clinicians and researchers to craft more impactful interventions to improve rates of alcohol abstinence and AUD treatment engagement.

Cannabis use in liver transplant candidates and recipients.

The increasing legality and acceptance of cannabis sale and consumption across the United States has led to a measurable increase in cannabis use nationwide, including in liver transplant (LT) candidates and recipients. With over 75% of liver transplant recipients transplanted in states with legalized use of medicinal and/or recreational cannabis, liver transplant clinicians must have expertise in the assessment of cannabis use given its potential impact on clinical care. In this review, the authors provide an understanding of nomenclature and tools to assess cannabis use, highlight essential components to guide clinical policy development and implementation, and discuss the potential impacts of cannabis use on patients' transplant course.

"But I didn't drink!": What to do with discordant phosphatidylethanol results.

Liver transplantation (LT) teams must be adept at detecting, evaluating, and treating patients' alcohol use, given its prominence among psychological and behavioral phenomena which cause and contribute to liver diseases. Phosphatidylethanol (PEth) is a highly useful alcohol biomarker increasingly recommended for routine use in hepatology and LT. PEth is unique among alcohol biomarkers because of its wide detection window, high sensitivity and specificity, and the correlation of its numerical value with different patterns of alcohol use. Alongside myriad clinical opportunities in hepatology and LT, PEth also confers numerous challenges: little guidance exists about its clinical use; fearing loss of LT access and the reactions of their clinicians and families, candidates and recipients are incentivized to conceal their alcohol use; and liver clinicians report lack of expertise diagnosing and treating substance-related challenges. Discordance between patient self-reported alcohol use and toxicology is yet another common and particularly difficult circumstance. This article discusses the general toxicological properties of PEth; explores possible scenarios of concordance and discordance among PEth results, patient history, and self-reported drinking; and provides detailed clinical communication strategies to explore discordance with liver patients, a key aspect of its use.

Reexamining "psychosocial clearance": A procedural framework for psychosocial evaluation in liver transplantation.

Psychosocial and "nonmedical" phenomena are commonly encountered in liver transplantation (LT) evaluations. They are simultaneously crucial decision-making factors and some of the most difficult and controversial clinical matters clinicians confront. Epidemiology, societal trends, and the preponderance of psychological and behavioral factors underpinning common end-stage liver diseases ensure that LT teams will continue to encounter highly complex psychosocial patient presentations. Psychosocial policies, practices, and opinions vary widely among clinicians and LT centers. Liver clinicians already report insufficient psychosocial expertise, which creates a large gap between the stark need for psychosocial expansion, improvement, and innovation in LT and the lack of accompanying guidance on how to achieve it. While the clinical domains of an LT psychosocial evaluation have been well-described, few articles analyze the procedures by which teams determine candidates' "psychosocial clearance" and no conceptual frameworks exist. This article proposes a framework of core domains of psychosocial evaluation procedures, common pitfalls, and practical improvement strategies.

New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease.

Alcohol use disorder remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for alcohol use disorder. In particular, changes in gut microbiota composition and function, and bile acid homeostasis, have been shown with alcohol consumption and cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors, in turn, promote liver and brain inflammation and the progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, for example, the ghrelin system (ghrelin receptor blockade), incretin mimetics (glucagon-like peptide-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of alcohol use disorder. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-associated burden of disease.

ACLP Best Practice Guidance: Evaluation and Treatment of Depression in Solid Organ Transplant Recipients.

We present Academy of Consultation Liaison Psychiatry best practice guidance on depression in solid organ transplant (SOT) recipients, which resulted from the collaboration of Academy of Consultation Liaison Psychiatry's transplant psychiatry special interest group and Guidelines and Evidence-Based Medicine Subcommittee. Depression (which in the transplant setting may designate depressive symptoms or depressive disorders) is a frequent problem among SOT recipients. Following a structured literature review and consensus process, the Academy of Consultation Liaison Psychiatry transplant psychiatry special interest group proposes recommendations for practice: all organ transplant recipients should be screened routinely for depression. When applicable, positive screening should prompt communication with the mental health treating provider or a clinical evaluation. If the evaluation leads to a diagnosis of depressive disorder, treatment should be recommended and offered. The recommendation for psychotherapy should consider the physical and cognitive ability of the patient to maximize benefit. The first-line antidepressants of choice are escitalopram, sertraline, and mirtazapine. Treating depressive disorders prior to transplantation is recommended to prevent posttransplant depression. Future research should address the mechanism by which transplant patients develop depressive disorders, the efficacy and feasibility of treatment interventions (both pharmacological and psychotherapeutic, in person and via telemedicine), and the resources available to transplant patients for mental health care.

Definition and measurement of alcohol-associated insight in early liver transplantation for acute alcohol-associated hepatitis: A systematic review.

BACKGROUND: Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are challenging because they rely on detailed psychosocial assessments and interpretations of psychiatric and substance use disorder data, which often must occur rapidly according to the acuity of end-stage liver disease. Such difficulties commonly occur during the process of candidate selection and liver allocation, particularly during early LT (eLT) in patients with acute alcohol-associated hepatitis (AAH). Patients with AAH commonly have very recent or active substance use, high short-term mortality, psychiatric comorbidities, and compressed evaluation and treatment timetables. LT clinicians report that patients' alcohol-associated insight (AAI) is among the most relevant psychosocial data in this population, yet no studies exist examining how LT teams define and use AAI in eLT or its effect on clinical outcomes. In April 2022, we searched Ovid MEDLINE, Elsevier Embase, EBSCOhost PsycInfo and CINAHL, and Wiley Cochrane Central Register of Controlled Trials for reports describing AAH populations who underwent eLT, which also described psychosocial evaluation parameters. The searches retrieved 1603 unique reports. After eligibility screening, 8 were included in the qualitative analysis. This systematic review reveals that AAI is a poorly defined construct that is not measured in a standardized way. Yet it is a commonly cited parameter in articles that describe the psychosocial evaluation and decision-making of patients undergoing eLT for AAH. This article also discusses the general challenges of assessing AAI during eLT for AAH, existing AAI definitions and rating scales, how AAI has been used to date in the broader hepatology and LT literature, and future areas for clinical and research progress.

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.

INTRODUCTION: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS: Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.