Assessing reliability and validity of SIPAT and opportunities for improvement: A single-center cohort study.

Psychosocial assessment is a standard component of patient evaluations for transplant candidacy. The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a widely used measure to assess psychosocial risk for transplant. However, there are questions regarding the SIPAT's reliability and validity. We examined the SIPAT's psychometric performance and its impact on equitable access to transplant in a diverse cohort of 2825 patients seeking liver transplantation between 2014 and 2021 at an urban transplant center. The SIPAT demonstrated good internal consistency reliability at the overall score [Cronbach's α = 0.85, 95% CI (0.83, 0.86)] and domain levels (0.80 > α > 0.70). There was mixed support for structural validity, with poor overall model fit in confirmatory factor analysis and 50% of questions achieving the 0.70-factor loadings threshold. Adjusting for sociodemographic variables, the odds of not being waitlisted for psychosocial reasons were three times higher for patients with Medicaid insurance than patients with private insurance [OR 3.24, 95% CI (2.09, 4.99)] or Medicare [OR 2.89, 95% CI (1.84, 4.53)], mediated by higher SIPAT scores. Black patients had nearly twice the odds of White patients [OR 1.88, 95% CI (1.20, 2.91)], partially mediated by higher social support domain scores. Patients with Medicaid, non-White patients, and those without a college degree scored significantly higher on collinear questions, disproportionately contributing to higher SIPAT scores. The SIPAT did not perform equally across insurance type, race/ethnicity, and education groups, with the lowest subgroup validity associated with patient readiness and psychopathology domains. The SIPAT should be interpreted with caution, especially as a composite score. Future studies should examine validity in other populations.

Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014-2021. The utility of the previously defined total SIPAT cut-off (<21 [excellent/good candidates] vs ≥21 [minimally acceptable/high risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT score and LT waitlisting outcomes. Youden's J statistic was used to identify the optimal SIPAT cut-off for MASLD patients. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median (IQR): 7.8 (6.0-9.7) vs 6.6 (5.8, 7.9); p=0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per five-point increase; p=0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cut-off in this population, resulting in an adjusted OR for listing of 0.53 vs SIPAT <12 (p=0.001). In this large cohort of MASLD patients evaluated for LT, few patients met the previously defined high SIPAT cut-off for transplant suitability. Nevertheless, increasing SIPAT score was associated with waitlist outcome. Our suggested SIPAT cut-off of ≥12 for MASLD patients warrants further external validation using data from other centers.

Therapeutic Pipeline in Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is a leading cause of mortality and morbidity worldwide. Patients with alcohol-associated liver disease are often diagnosed at advanced stage and disease spectrum including alcoholic hepatitis, a severe manifestation with a high short-term mortality. Corticosteroid, recommended first-line treatment for patients with alcoholic hepatitis, is a very suboptimal treatment. Although the use of early liver transplantation has increased with consistent benefit in select patients with alcoholic hepatitis, its use remains heterogeneous worldwide due to lack of uniform selection criteria. Over the last decade, several therapeutic targets have evolved of promise with ongoing clinical trials in patients with cirrhosis and alcoholic hepatitis. Even with availability of effective medical therapies for alcohol-associated liver disease, long-term outcome depends on abstinence from alcohol use in any spectrum of alcohol-associated liver disease. However, alcohol use disorder treatment remains underutilized due to several barriers even in patients with advanced disease. There is an urgent unmet need to implement and promote integrated multidisciplinary care model with hepatologists and addiction experts to provide comprehensive management for these patients. In this review, we will discuss newer therapies targeting liver disease and therapies targeting alcohol use disorder in patients with alcohol-associated liver disease.

Racial and ethnic disparities in psychosocial evaluation and liver transplant waitlisting.

Health disparities have been well-described in all stages of the liver transplantation (LT) process. Using data from psychosocial evaluations and the Stanford Integrated Psychosocial Assessment, our objective was to investigate potential racial and ethnic inequities in overall LT waitlisting and not waitlisting for medical or psychosocial reasons. In a cohort of 2271 candidates evaluated for LT from 2014 to 2021 and with 1-8 years of follow-up, no significant associations were noted between race/ethnicity and overall waitlisting and not waitlisting for medical reasons. However, compared with White race, Black race (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07-2.56) and Hispanic/Latinx ethnicity (OR, 2.10; 95% CI, 1.16-3.78) were associated with not waitlisting for psychosocial reasons. After adjusting for sociodemographic variables, the relationship persisted in both populations: Black (OR, 1.95; 95% CI, 1.12-3.38) and Hispanic/Latinx (OR, 2.29; 95% CI, 1.08-4.86) (reference group, White). High-risk Stanford Integrated Psychosocial Assessment scores were more prevalent in Black and Hispanic/Latinx patients, likely reflecting upstream factors and structural racism. Health systems and LT centers should design programs to combat these disparities and improve equity in access to LT.

The Ongoing Debate of Serum Ammonia Levels in Cirrhosis: the Good, the Bad, and the Ugly.

Serum ammonia testing in hepatic encephalopathy (HE) has been long debated in the field of hepatology. Although central to the pathophysiology of HE, serum ammonia testing is fraught with complexities that can lead to challenges in laboratory collection and interpretation. Although there is some disagreement across guideline organizations regarding routine testing of ammonia in HE, all acknowledge that normal values, although possible in HE, may warrant reconsideration of the diagnosis. In this study, we propose a nuanced approach to ammonia testing in HE. Serum ammonia testing provides little additional benefit in clinical scenarios with a high or low pretest probability for HE. However, if the pretest probability for HE is uncertain, a low ammonia level may reduce the posttest probability of HE. In this scenario, other etiologies of altered mental status should be explored. Future research should focus on developing a standardized approach to serum ammonia collection, processing, and interpretation.

Race-based differences in drug use prior to onset of opioid use disorder.

Rates of opioid use disorder (OUD) have increased dramatically over the past two decades, a rise that has been accompanied by changing demographics of those affected. Early exposure to drugs is a known risk factor for later development of opioid use disorder; but how and whether this risk factor may differ between racial groups is unknown. Our study seeks to identify race differences in self-report of current and past substance use in OUD-diagnosed treatment-seeking individuals. Patients (n = 157) presenting for methadone maintenance treatment at a racially diverse urban opioid treatment program were approached and consented for study involvement. Participants were administered substance use history questionnaires and urine drug screening at intake. Chi-square, t-tests, and rank-sum were used to assess race differences in demographic variables. Logistic and linear regressions assessed the relationship between race and substance use for binary and continuous variables, respectively. 61% of the population identified as Black and 39% as White. Black participants were significantly older; age was thus included as a covariate. Logistic regressions demonstrated that despite similar urine toxicology at intake, White participants were significantly more likely to report having used prescription opioids and psychedelic, stimulant, and sedative substance classes prior to their first use of non-pharmaceutical opioids. Compared to Black participants, White treatment-seeking OUD-diagnosed individuals reported using a wider range of substances ever and prior to first use of non-pharmaceutical opioids. There were no differences, however, in presentation for OUD treatment, suggesting different pathways to OUD, which may carry important clinical implications.

Alcohol-Associated Liver Disease Mortality Increased From 2017 to 2020 and Accelerated During the COVID-19 Pandemic.

Alcohol consumption has risen substantially in the United States in the past 2 decades.1,2 Alcohol-associated liver disease (ALD) represents a greater inpatient financial burden than all other etiologies of cirrhosis combined3 and is now the leading indication for liver transplantation.4 A recent study reported that ALD mortality increased between 2006 and 2017.5 Since 2017, alcohol consumption has continued to rise, and more significantly during the COVID-19 pandemic.2 The aim of this research letter is to provide the most updated trends in ALD-related mortality in the United States and to quantify the rate of change of ALD-related mortality over time.

The Stanford Integrated Psychosocial Assessment for Transplant Is Associated With Outcomes Before and After Liver Transplantation.

The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a standardized psychosocial evaluation tool used in liver transplantation (LT) evaluation. We assessed the impact of the SIPAT score and subdomains on transplant waitlisting decisions and post-LT outcomes including immunosuppression (IS) nonadherence, biopsy-proven rejection, andmortality/graft failure. We conducted a single-center observational cohort study of 1430 patients evaluated for LT. Patients were divided in 2 groups based on a SIPAT cutoff score of <21 or ≥21 (higher SIPAT scores indicate higher psychosocial risk). Regression models assessed relationships between total SIPAT score and domain scores and waitlisting decisions, IS nonadherence, allograft rejection, and death/graft failure. Elevated total SIPAT and SIPAT domain scores were associated not being added to the waitlist (total SIPAT core ≥21 adjusted odds ratio [aOR], 1.78 [95% confidence interval, CI, 1.36-2.33]; readiness score ≥5 aOR, 2.01 [95% CI, 1.36-2.76]; social support score ≥4aOR, 1.50 [95% CI, 1.15-1.94]; psychopathology score ≥7 aOR, 1.45 [95% CI, 1.07-1.94]; lifestyle/substance abuse score ≥12 aOR, 1.72 [95%CI, 1.23-2.39]) and were more likely to experience IS nonadherence as measured by the tacrolimus coefficient of variation (CoV) (total SIPAT score ≥21 aOR, 2.92 [95% CI, 1.69-5.03]; readiness score ≥5 aOR, 3.26 [95% CI, 1.63-6.52]; psychopathology score ≥7 aOR, 1.88 [95% CI, 1.00-3.50]; lifestyle substance abuse score ≥12 aOR, 3.03 [95% CI, 1.56-5.86]). SIPAT readinessscore ≥5 was associated with biopsy-proven allograft rejection (aOR, 2.66; 95% CI, 1.20-5.91). The SIPAT score was independently associated with LT listing decisions and IS nonadherence, and the readiness domain was associated with the risk of allograft rejection. These findings offer insights into higher risk recipients who require additional support before and aftertransplantation.

Prior Relapse, Ongoing Alcohol Consumption, and Failure to Engage in Treatment Predict Alcohol Relapse After Liver Transplantation.

BACKGROUND: Alcohol-related liver disease (ALD) is the leading indication for liver transplantation (LT) in the USA. Alcohol relapse post-LT can negatively impact long-term outcomes, and prognostic scoring systems are available for further study. AIMS: Our study aims were to: (1) evaluate the relationship between alcohol relapse and rejection and mortality, (2) investigate risk factors for relapse, and (3) assess predictive validity of the SIPAT (Stanford Integrated Psychosocial Assessment for Transplant) and SALT (Sustained Alcohol Use Post-Liver Transplant) scores on post-LT alcohol relapse. METHODS: We conducted a retrospective chart review of 155 patients transplanted for chronic ALD at a single transplant center. Cox proportional hazard models assessed the relationship between alcohol relapse and allograft rejection and psychosocial risk factors for relapse. RESULTS: 20% of patients met criteria for alcohol relapse. Alcohol relapse was associated with allograft rejection (HR 2.33, 95% CI 1.11-4.91, p = .03). Three variables most strongly associated with alcohol relapse: prior relapse, failure to engage in recommended alcohol treatment, and continued drinking with liver disease, which were combined into a psychosocial model. SIPAT score≥ 21 and SALT score ≥ 7 were associated with alcohol relapse (HR 6.40, 95% CI 1.36-30.18, p = .019 and HR 2.30, 95% CI 1.12-4.75, p = .024). Receiver operator characteristic analysis compared predictive ability of our psychosocial model to SIPAT (C-statistic .83 compared to .71) and SALT (C-statistic = .77 compared to .62). CONCLUSION: We identified important psychosocial predictors of post-LT alcohol relapse and validated SIPAT and SALT scores as pre-transplant risk factors for alcohol relapse.

A Comprehensive Review of Hepatic Sarcoid.

Sarcoidosis is a multisystem inflammatory disease, which is characterized by the development of noncaseating granulomas amid healthy tissue. While most commonly affecting the mediastinum and/or lungs, sarcoid can also affect the liver, resulting in "hepatic sarcoid." The spectrum of disease in hepatic sarcoid is variable, ranging from asymptomatic or mild liver enzyme abnormalities to end-stage liver disease requiring liver transplantation. Because clinically-significant hepatic sarcoid is rare, research on epidemiology, clinical manifestations, and treatment is limited. The mainstays of hepatic sarcoid treatment have involved steroids and more recently, ursodeoxycholic acid; however, novel immunomodulatory agents provide new possibilities for management. Questions remain regarding screening, diagnostic modalities, and what to treat with and when. The purpose of this review is to summarize the available research on the epidemiology, clinical course, and management of hepatic sarcoid, and identify gaps in our knowledge to motivate future research.

Closing the Care Gap: Management of Alcohol Use Disorder in Patients with Alcohol-associated Liver Disease.

Alcohol-associated liver disease (ALD)-related morbidity and mortality are rising in the United States. Although effective medications and behavioral interventions are available for the treatment of patients with alcohol use disorder (AUD), patients with ALD are profoundly undertreated for AUD. This article reviews the management of AUD in patients with ALD, with a focus on appropriate screening and diagnosis, management of alcohol withdrawal syndrome, pharmacotherapy for AUD, alcohol biomarkers, and behavioral interventions. Expanding access to AUD treatment is imperative for improving health outcomes in patients with ALD.

Covid-19 and alcohol associated liver disease.

The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden.

Serum Ammonia in Cirrhosis: Clinical Impact of Hyperammonemia, Utility of Testing, and National Testing Trends.

PURPOSE: Ammonia is central to the pathophysiology of hepatic encephalopathy (HE) in cirrhosis. Serum ammonia levels have prognostic value and have been implicated in sarcopenia, hepatotoxicity, and immune dysfunction. Studies indicate that clinicians frequently order serum ammonia levels in decompensated cirrhosis; however, the clinical utility of serum ammonia levels has been questioned, citing challenges in accurate measurement and interpretation. This article involves a primary review of the literature to evaluate the importance of serum ammonia in cirrhosis and examines the clinical utility of serum ammonia levels in the management of HE. In addition to the review, we conducted primary research using national claims data to investigate national trends in practitioner use of serum ammonia. METHODS: We identified all hospitalizations in a national commercial claims database with and without ammonia testing among adults with noncirrhotic chronic liver disease and cirrhosis from January 1, 2007, to September 31, 2015. We calculated the proportion of hospitalizations with ammonia testing and the number of ammonia tests per 1000 hospital-days. FINDINGS: Proportion of hospitalizations with ammonia testing and ammonia tests per 1000 inpatient-days increased significantly from 2007 to 2015, and particularly in 2014 and 2015, for all groups. IMPLICATIONS: A review of the literature indicated that elevated serum ammonia contributes to neurotoxicity, sarcopenia, and immune dysfunction in cirrhosis. However, serum ammonia testing has not had consistent benefit in clinical diagnosis or management of HE in cirrhosis. Claims data indicated that ammonia testing increased substantially during the study period, particularly after the advent of electronic medical record systems. The rapid increase in testing may suggest that electronic health records play a crucial role in test volume by facilitating easy ordering and could be leveraged to improved value-based serum ammonia ordering. Serum ammonia levels may also benefit from standardized guidelines on collection, laboratory analysis, and interpretation.

Individuals with Borderline Personality Disorder show larger preferred social distance in live dyadic interactions.

Personal space regulation is a key component of effective social engagement. Personal space varies among individuals and with some mental health conditions. Simulated personal space intrusions in Borderline Personality Disorder (BPD) reveal larger preferred interpersonal distance in that setting. These findings led us to conduct the first test of live interpersonal distance preferences in symptoms in BPD. With direct observation of subjects' personal space behavior in the stop-distance paradigm, we found a 2-fold larger preferred interpersonal distance in BPD than control (n = 30, n = 23). We discuss this result in context of known biology and etiology of BPD. Future work is needed to identify neural circuits underlying personal space regulation in BPD, individual differences in preferred interpersonal distance in relation to specific symptoms and relationship to recovery status.