Psychiatric diagnoses are common after liver transplantation and associated with increased healthcare utilization and patient financial burden.

INTRODUCTION: Psychiatric disorders after liver transplantation (LT) are associated with worse patient and graft outcomes, which may be amplified by inadequate treatment. We aimed to characterize the burden of psychiatric disorders, treatment patterns, and associated financial burden among LT recipients (LTRs). METHODS: IQVIA PharMetrics® Plus for Academics-a large health plan claims database representative of the commercially insured U.S. population-was used to identify psychiatric diagnoses among adult LTRs and assess treatment. Multivariable logistic regression analysis identified factors associated with post-LT psychiatric diagnoses and receipt of pharmacotherapy. Patient financial liability was estimated using adjudicated medical/pharmacy claims for LTRs with and without psychiatric diagnoses. RESULTS: Post-LT psychiatric diagnoses were identified in 395 (29.5%) of 1,338 LTRs, of which 106 (26.8%) were incident cases. Treatment varied, with 67.3% receiving pharmacotherapy, 32.1% psychotherapy, 21.0% combination therapy, and 21.5% no treatment. Among 340 LTRs on psychotropic medications before transplant, 24% did not continue them post-LT. Post-LT psychiatric diagnoses were independently associated with female sex, alcohol-associated liver disease (ALD), prolonged LT hospitalization (>2 weeks), and pre-LT psychiatric diagnosis. Incident psychiatric diagnoses were associated with female sex, ALD, and prolonged LT hospitalization. Patients with a post-LT psychiatric diagnosis had higher rates of hospitalization (89.6% vs 81.5%, p<0.001) and financial liability (median $5.5K vs $4.6K USD, p=0.006). Having a psychiatric diagnosis post-LT was independently associated with experiencing high financial liability >$5K. CONCLUSION: Over 1 in 4 LTRs had a psychiatric diagnosis in a large national cohort, yet nearly a quarter received no treatment. LTRs with psychiatric diagnoses experienced increased healthcare utilization and higher financial liability. Sociodemographic and clinical risk factors could inform high-risk subgroups who may benefit from screening and mitigation strategies.

Management of alcohol-associated liver disease and alcohol use disorder in liver transplant candidates and recipients: Challenges and opportunities.

Alcohol-associated liver disease poses a significant global health burden, with rising alcohol consumption and prevalence of alcohol use disorder (AUD) contributing to increased morbidity and mortality. This review examines the challenges and opportunities in the care of candidates and recipients of liver transplant (LT) with AUD. Despite advancements in posttransplant patient survival, the risk of disease recurrence and alcohol relapse remains substantial. Several challenges have been identified, including (1) rising disease burden of alcohol-associated liver disease, variable transplant practices, and systemic barriers; (2) disparities in mental health therapy access and the impact on transplant; (3) variable definitions, underdiagnosis, and stigma affecting access to care; and (4) post-LT relapse, its risk factors, and consequential harm. The review focuses on the opportunities to improve AUD care for candidates and recipients of LT through effective biochemical monitoring, behavioral and pharmacologic approaches, creating Centers of Excellence for post-LT AUD care, advocating for policy reforms, and ensuring insurance coverage for necessary services as essential steps toward improving patient outcomes. The review also highlights unmet needs, such as the scarcity of addiction specialists, and calls for further research on personalized behavioral treatments, digital health, and value-based care models to optimize AUD care in the LT setting.

"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.

National survey of second opinions for hospitalized patients in need of liver transplantation.

Decisions about patient candidacy for liver transplant (LT) can mean the difference between life and death. We surveyed LT centers across the United States to assess their perceptions of and barriers to second-opinion referrals for inpatients declined for transplant. The medical and surgical directors of 100 unique US LT programs that had done >20 LTs in 2021 were surveyed with a 33-item questionnaire including both multiple-choice and free-response questions. The response rate was 60% (60 LT centers) and included 28 larger-volume ( ≥100 LTs in 2021) and 32 smaller-volume (<100 LTs in 2021) programs. The top 3 reasons for inpatient denial for LT included lack of social support (21%), physical frailty (20%), and inadequate remission duration from alcohol use (11%). Twenty-five percent of the programs reported "frequently" facilitating a second opinion for a declined inpatient, 52% of the programs reported "sometimes" doing so, and 7% of the programs reported never doing so. One hundred percent of the programs reported that they receive referrals for second opinions. Twenty-five percent of the programs reported transplanting these referrals frequently (over 20% of the time). Neither program size nor program location statistically impacted the findings. When asked if centers would be in favor of standardizing the evaluation process, 38% of centers would be in favor, 39% would be opposed, and 23% were unsure. The practices and perceptions of second opinions for hospitalized patients evaluated for LT varied widely across the United States. Opportunities exist to improve equity in LT but must consider maintaining individual program autonomy.

Rethinking Second Chances: When Rejected Liver Transplant Candidates Seek Reevaluation Elsewhere.

AbstractLiver transplantation offers a lifesaving treatment for patients suffering from end-stage liver failure, but not all candidates in the United States are eligible owing to center-specific criteria. When a patient is rejected at a transplantation center for medical, surgical, or psychosocial issues, they are often referred to other centers. We focus on this practice of reevaluation at a second center when the candidate was rejected for psychosocial reasons. We review the criteria used by health professionals to determine psychosocial eligibility and present three case examples from a large teaching hospital that demonstrate this phenomenon in practice. The cases illustrate the conflicts among autonomy, beneficence, nonmaleficence, and justice. We present arguments for and against this practice and provide concrete solutions as a path forward.

An Assessment of the Psychosocial Evaluation for Early Liver Transplantation in Patients With Acute Alcoholic Hepatitis in the Context of Alcohol Use Disorder, a Case-Control Study.

Background: Severe acute alcoholic hepatitis (AAH) has an extremely poor prognosis with a high short term mortality rate. As a result, many centers, including our own, have allowed transplant patients to be listed for transplantation prior to achieving 6-months of sobriety. Several scoring systems, designed to target patients with a minimal period of sobriety, have been proposed to identify patients with alcohol use disorder (AUD), who would be predisposed to relapse after liver transplantation. We investigated whether these scoring systems corroborated the results of the non-structured selection criteria used by our center regarding decision to list for transplant. Methods: We conducted a retrospective case-control study of 11 patients who underwent early liver transplantation for AAH matched with 11 controls who were declined secondary to low insight into AUD. Blinded raters confirmed the severity of the diagnosis of DSM-5 and scored the patients on a variety of structured psychometric scales used to predict alcohol relapse. These included the High Risk for Alcohol Relapse Scale (HRAR), Stanford Integrated Psychosocial Assessment Tool (SIPAT), Alcohol Relapse Risk Assessment (ARRA), Hopkins Psychosocial Scale (HPSS), Michigan Alcoholism Prognosis Score (MAPS), Alcohol Use Disorders Identification Test -Consumption (AUDIT-C), and Sustained Alcohol Use Post-Liver Transplant (SALT) scales. All patients who underwent transplantation were followed for harmful and non-harmful drinking until the end of the study period. Results: The transplant recipients had significantly favorable MAPS, HRAR, SIPAT, ARRA, and HPSS scores with cutoffs that matched their previous research. The SALT and AUDIT-C scores were not predictive of our selection of patients for transplantation. Despite an expedited evaluation and no significant period of sobriety, our case cohort had a 30% relapse to harmful drinking after an average of 6.6 years (5-8.5 years) of follow-up. Discussion: Despite the rapid assessment and the short to no period of sobriety, the patient cohort demonstrated a 30% relapse to harmful drinking, consistent with the 20% to 30% relapse to drinking rate reported after liver transplantation for all forms of alcoholic liver disease. Average scores from MAPS, HRAR, SIPAT, ARRA, and HPSS corroborated our current stratification procedures, with lower mean risk scores found in the transplanted group. Conclusion: Patients with AUD and severe AAH who obtain new insight into their disease and posses other favorable psychosocial factors have low rates of AUD relapse post-liver-transplantation. The psychosocial selection criteria for patients with alcoholic hepatitis in our institution are consistent with 4 of the 5 scoring systems investigated in their prediction of sobriety post-transplant.

Multimodal multidisciplinary management of alcohol use disorder in liver transplant candidates and recipients.

Alcohol-related liver disease (ALD) is the most common indication for liver transplantation (LT) in the United States. The judicious allocation of organs and improvement in outcomes requires identification and monitoring of patients with ALD at high-risk for relapse post-transplantation. The controversial movement toward early LT for severe alcohol-related hepatitis (SAH) has also raised concern for alcohol relapse. While LT cures ALD, treatment of alcohol use disorder (AUD) must be included in the care plan to prevent a return to drinking and subsequent graft ALD. Patients with underlying AUD must be recognized, offered brief interventions and referred for multimodal multidisciplinary treatment that includes medications and psychotherapies along with sober support groups, family engagement, and a new dedication to healthy living in order to help sustain remission. Such comprehensive care will increase LT candidacy in patients with ALD while optimizing clinical outcomes of patients transplanted with AUD.

Cannabinoids and solid organ transplantation: Psychiatric perspectives and recommendations.

Cannabinoid use in patients seeking solid organ transplantation (SOT) is an important and unsettled matter which all transplantation clinicians regularly encounter. It is also a multifaceted, interprofessional issue, difficult for any specialty alone to adequately address in a research article or during clinical care. Such uncertainty lends itself to bias for or against cannabinoid use accompanied by inconsistent policies and procedures. Scientific literature in SOT regarding cannabinoids often narrowly examines the issue and exists mostly in liver and kidney transplantation. Published recommendations from professional societies are mosaics of vagueness and specificity mirroring the ongoing dilemma. The cannabinoid information SOT clinicians need for clinical care may require data and perspectives from diverse medical literature which are rarely synthesized. SOT teams may not be adequately staffed or trained to address various neuropsychiatric cannabinoid effects and risks in patients. In this article, authors from US transplantation centers conduct a systematized review of the few existing studies regarding clinician perceptions, use rates, and clinical impact of cannabinoid use in SOT patients; collate representative professional society guidance on the topic; draw from diverse medical literature bases to detail facets of cannabinoid use in psychiatry and addiction pertinent to all transplantation clinicians; provide basic clinical and policy recommendations; and indicate areas of future study.

Artificial intelligence to identify harmful alcohol use after early liver transplant for alcohol-associated hepatitis.

Early liver transplantation (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT, but prediction of harmful alcohol use post-LT remains limited. Among 10 ACCELERATE-AH centers, we examined psychosocial evaluations from consecutive LT recipients for AH from 2006 to 2017. A multidisciplinary panel used content analysis to develop a maximal list of psychosocial variables. We developed an artificial intelligence model to predict post-LT harmful alcohol use. The cohort included training (N = 91 among 8 centers) and external validation (N = 25 among 2 centers) sets, with median follow-up of 4.4 (IQR 3.0-6.0) years post-LT. In the training set, AUC was 0.930 (95%CI 0.862-0.998) with positive predictive value of 0.891 (95%CI 0.620-1.000), internally validated through fivefold cross-validation. In the external validation set, AUC was 0.692 (95%CI 0.666-0.718) with positive predictive value of 0.82 (95%CI 0.625-1.000). The model identified specific variables related to social support and substance use as highly important to predict post-LT harmful alcohol use. We retrospectively developed and validated a model that identified psychosocial profiles at LT predicting harmful alcohol use post-LT for AH. This preliminary model may inform selection and post-LT management for AH and warrants prospective evaluation in larger studies among all alcohol-associated liver disease being considered for early LT.

The use of nondirected donor organs in living donor liver transplantation: Perspectives and guidance.

Interest in anonymous nondirected living organ donation is increasing in the United States and a small number of transplantation centers are accumulating an experience regarding nondirected donation in living donor liver transplantation. Herein, we review current transplant policy, discuss emerging data, draw parallels from nondirected kidney donation, and examine relevant considerations in nondirected living liver donation. We aim to provide a consensus guidance to ensure safe evaluation and selection of nondirected living liver donors and a schema for just allocation of nondirected grafts.

Scoring systems to assess relapse risk in alcohol use disorder presenting for early liver transplantation: A systematic review.

OBJECTIVE: Early liver transplantation (LT) is considered for patients with alcohol use disorder (AUD) despite limited sober time when acute mortality risk from liver disease is high. The objective of this paper is to find psychosocial tools that do not rely on extended sober time and predict alcohol relapse post-LT. METHODS: We conducted a systematic review of Pubmed, Embase, and Scopus for studies testing psychosocial tools that used numeric scoring to predict post-LT alcohol relapse. Tools that afforded points for length of sobriety were excluded. Each study was analyzed for its clinical context, post-LT relapse outcomes and predictive validity. RESULTS: Five scoring systems across fourteen samples showed varied validity in predicting post-LT alcohol relapse. Relapse to any alcohol use after LT revealed an average relapse rate of 23%. Most scoring systems were understudied but four of five provided cut-off scores with high negative predictive values for relapse. CONCLUSION: Scoring systems may have a place in candidate selection but the data on cut-off scores and predictability are still lacking for their use alone in high stakes LT selection. Larger studies with prospective scoring and standardized follow ups for relapse post-LT will better allow the predictive validity of these psychosocial tools to be compared.

Identification of Quantifiable Predictors of Relapse in Patients with Alcohol-Associated Liver Disease.

Abstinence in patients with alcohol-associated liver disease (ALD) reduces mortality. Most predictors of relapse are not quantifiable, preventing objective analysis of relapse risk and targeted intervention to improve clinical outcomes. We prospectively enrolled patients with ALD from November 2016 to December 2019 and administered a survey with two previously published scales to assess insight into alcohol-use disorder (Hanil Alcohol Insight Scale [HAIS]) and social support (Community Assessment Inventory Scale [CAIS]). Relapse was assessed using surveys and metabolite testing. Unadjusted and prespecified adjusted regression analyses identified predictors of relapse. We enrolled 81% of eligible patients (n = 136), of whom 58 had follow-up data available at the time of analysis. Over a median follow-up of 1 year (interquartile range: 0.5-1.4), 10 patients relapsed (17%). Patients who relapsed were more likely to continue drinking despite either a diagnosis of liver disease or a decompensating event, and were less likely to have been transplanted (all P < 0.05). In unadjusted regression, the HAIS and the "support inside the home" subcategory of the CAIS were predictive of relapse, with odds ratio (OR) = 0.84 (95% confidence interval 0.72-0.97) and 0.85 (0.74-0.97). In adjusted regression, the HAIS was no longer significant, with adjusted OR = 0.70 (0.49-1.00, P = 0.05), whereas the "support inside the home' subcategory of CAIS remained significant, with adjusted OR = 0.69 (0.51-0.92, P = 0.01). Conclusions: Risk factors for relapse in patients with ALD were identified and quantified prospectively, suggesting opportunities to objectively identify patients at risk for relapse as well as to intervene to prevent relapse.

Feature-Based Machine Learning Model for Real-Time Hypoglycemia Prediction.

BACKGROUND: Hypoglycemia is a serious health concern in youth with type 1 diabetes (T1D). Real-time data from continuous glucose monitoring (CGM) can be used to predict hypoglycemic risk, allowing patients to take timely intervention measures. METHODS: A machine learning model is developed for probabilistic prediction of hypoglycemia (<70 mg/dL) in 30- and 60-minute time horizons based on CGM datasets obtained from 112 patients over a range of 90 days consisting of over 1.6 million CGM values under normal living conditions. A comprehensive set of features relevant for hypoglycemia are developed and a parsimonious subset with most influence on predicting hypoglycemic risk is identified. Model performance is evaluated both with and without contextual information on insulin and carbohydrate intake. RESULTS: The model predicted hypoglycemia with >91% sensitivity for 30- and 60-minute prediction horizons while maintaining specificity >90%. Inclusion of insulin and carbohydrate data yielded performance improvement for 60-minute but not for 30-minute predictions. Model performance was highest for nocturnal hypoglycemia (~95% sensitivity). Shortterm (less than one hour) and medium-term (one to four hours) features for good prediction performance are identified. CONCLUSIONS: Innovative feature identification facilitated high performance for hypoglycemia risk prediction in pediatric youth with T1D. Timely alerts of impending hypoglycemia may enable proactive measures to avoid severe hypoglycemia and achieve optimal glycemic control. The model will be deployed on a patient-facing smartphone application in an upcoming pilot study.

The Utility of a Pre-Transplant Psychosocial Evaluation in Predicting Post-Liver Transplant Outcomes.

BACKGROUND: There is insufficient evidence about the ability of pretransplant psychosocial evaluations to predict posttransplant outcomes. While standardized assessments were developed to increase predictive validity, it is unclear whether the risk scores they yield predict outcomes. We investigated if the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), a scaling approach to those assessments, would have been a superior predictor than the standard psychosocial evaluation. METHODS: In this retrospective study, medical records of 182 adult liver transplant recipients who were at least 1 year posttransplant and prescribed tacrolimus for immunosuppression were analyzed. Regression analyses predicted outcomes of interest, including immunosuppressant nonadherence and biopsy-proven rejection, obtained 1-year posttransplant to time of data collection. Nonadherence was determined using the medication level variability index (MLVI). RESULTS: Approximately 49% of patients had MLVI > 2.5, suggestive of nonadherence, and 15% experienced rejection. SIPAT total score did not predict adherence either using the continuous (P = .70), or dichotimized score, above or below > 2.5 (P = .14), or rejection (P = 0.87). Using a SIPAT threshold (total score > 69) did not predict adherence (p = .16) nor was a superior predictor of the continuous adherence score (P = .45), MLVI > 2.5 (P = .42), or rejection (P = 0.49), than the standard evaluation. CONCLUSION: Our findings suggest that the SIPAT is unable to predict 2 of the most important outcomes in this population, immunosuppressant adherence and rejection. Research efforts should attempt to evaluate the best manner to use psychosocial evaluations.

Depression, Anxiety, and Acute Stress Disorder Among Patients Hospitalized With COVID-19: A Prospective Cohort Study.

BACKGROUND: The epidemiology of psychiatric symptoms among patients with coronavirus disease 2019 is poorly characterized. OBJECTIVE: This article sought to identify the prevalence of anxiety, depression, and acute stress disorder among hospitalized patients with coronavirus disease 2019. METHODS: Adult patients recently admitted to nonintensive care unit medical ward settings with coronavirus disease 2019 were eligible for enrollment. Enrolled patients were screened for depression, anxiety, and delirium. Subsequently, patients were followed up by phone after 2 weeks and rescreened for depression, anxiety, and acute stress disorder symptoms. Subjects' medical records were abstracted for clinical data. RESULTS: A total of 58 subjects were enrolled; of whom, 44 completed the study. Initially, 36% of subjects had elevated anxiety symptoms and 29% had elevated depression symptoms. At 2-week follow-up, 9% had elevated anxiety symptoms, 20% had elevated depression symptoms, and 25% had mild-to-moderate acute stress disorder symptoms. Discharge to home was not associated with improvement in psychiatric symptoms. CONCLUSIONS: A significant number of patients hospitalized with coronavirus disease 2019 experienced symptoms of depression and anxiety. While anxiety improved after index admission, depression remained fairly stable. Furthermore, a significant minority of patients experienced acute stress disorder symptoms, though these were largely mild to moderate.

Alcohol and other substance use after liver transplant.

In this article we tackle the controversial subject of alcohol and other substance use following liver transplantation (LT). Most of the literature on and importance of this topic pertains not to recreational use of alcohol or substances but to patients who have alcohol or substance use disorders (AUDs/SUDs). To understand these behaviors after such a lifesaving and resource-intensive procedure as LT necessitates an understanding of these disorders as chronic medical diseases. It also requires an awareness that management of these disorders begins before transplant, so we will briefly touch on considerations to prepare patients for the transplantation. Additionally, we review not only the rates of alcohol and substance use post-LT but strategies clinicians could adopt to identify and manage these events post-LT. Thus, we will summarize approaches for monitoring use and a range of therapeutic treatment options, including pharmacotherapy, to employ once use is discovered. While clinical gastroenterologists may be the primary clinicians responsible for the care of LT recipients, we emphasize a multidisciplinary team approach which, especially for the behavioral health components of the treatment, is likely to be the most successful. This article concludes with a summary of recommendations for clinicians working with these patients and possible future directions for both clinical care and research. While the bulk of the literature is on LT in the context of AUD, we review the smaller body of literature available on non-alcohol substance use.