The Impact of Donor Body Mass Index on Safety and Outcomes in Living Donor Liver Transplantation: An Analysis of the National United States Database.

Background: The prevalence of obesity is rising in the general population. Donor obesity (body mass index ≥30 kg/m2) may potentially reduce the donor pool and impact outcomes in living donor liver transplantation (LDLT). Methods: We utilized the national transplant database to investigate the impact of donor obesity on donor and recipient outcomes. This was a retrospective cohort study of all LDLTs performed in the United States between January 2010 and June 2023. Outcomes of interest were analyzed by univariable and multivariable logistic regression. Patient and graft survival was evaluated using Kaplan-Meier and Cox proportional analysis. Results: Six hundred seventy-four donors with obesity and 3498 donors without obesity were analyzed. Donors with obesity had higher rates of readmission within 1 y of donation (15.9% versus 11.6%; P = 0.003). The risk of readmission was significantly different between 6 wk and 6 mo of donation (8.8% versus 5.9%; P = 0.036). Donor body mass index (odds ratio [OR], 1.460; 95% confidence interval [CI], 1.129-1.999; P = 0.004) and preoperative alkaline phosphatase levels (OR, 1.005; 95% CI, 1.000-1.011; P = 0.038) were independent predictors of donor readmission. High LDLT center volume was associated with reduced odds of donor readmission (OR, 0.509; 95% CI, 0.373-0.694; P < 0.001). Graft and recipient survival was comparable. Conclusions: Selection of living donors with obesity may be a potential avenue to increase the available donor pool without compromising recipient outcomes; however, they are at an increased risk for readmission between 6 wk and 6 mo of donation. The reason for readmission requires further study.

A Tailored Virtual Program for Alcohol Use Disorder Treatment Among Liver Transplant Candidates and Recipients Is Feasible and Associated With Lower Post-Transplant Relapse.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading indication for liver transplant (LT) in the United States. Rates of early liver transplant (ELT) with less than 6 months of sobriety have increased substantially. Patients who receive ELT commonly have alcohol-associated hepatitis (AH) and are often too ill to complete an intensive outpatient program (IOP) for alcohol use disorder (AUD) prior to LT. ELT recipients feel alienated from traditional IOPs. METHODS: We implemented Total Recovery-LT, a tailored virtual outpatient IOP specific for patients under evaluation or waitlisted for LT who were too ill to attend community-based alcohol treatment programs. The 12-week program consisted of weekly group and individual counseling delivered by a master's level Certified Addiction Counselor trained in the basics of LT.  Treatment consisted of 12-Step Facilitation, Motivational Interviewing, and Cognitive Behavioral Therapy. We report on program design, implementation, feasibility and early outcomes. RESULTS: From March 2021 to September 2022, 42 patients (36% female, 23 in LT evaluation, 19 post-transplant) enrolled across five cohorts with 76% (32/42) completing the program. Alcohol relapse was more common among noncompleters versus those who completed the program (8/10, 80% vs. 7/32, 22%, p = 0.002). History of trauma or post-traumatic stress symptoms were associated with lower likelihood of completion. Patients' desire for continued engagement after completion led to the creation of a monthly alumni group. CONCLUSIONS: Our integrated IOP model for patients with high-risk AUD in LT evaluation or post-transplant is well-received by patients and could be considered a model for LT programs.

Hospitalizations for opportunistic infections following transplantation and associated risk factors: A national cohort study of Medicare beneficiaries.

BACKGROUND: Opportunistic infections (OIs) are a significant cause of morbidity and mortality after organ transplantation, though data in the liver transplant (LT) population are limited. METHODS: We performed a retrospective cohort study of LT recipients between January 1, 2007 and Deceber 31, 2016 using Medicare claims data linked to the Organ Procurement and Transplantation Network database. Multivariable Cox regression models evaluated factors independently associated with hospitalizations for early (≤1 year post transplant) and late (>1 year) OIs, with a particular focus on immunosuppression. RESULTS: There were 11 320 LT recipients included in the study, of which 13.2% had at least one OI hospitalization during follow-up. Of the 2638 OI hospitalizations, 61.9% were early post-LT. Cytomegalovirus was the most common OI (45.4% overall), although relative frequency decreased after the first year (25.3%). Neither induction or maintenance immunosuppression were associated with early OI hospitalization (all p > .05). The highest risk of early OI was seen with primary sclerosing cholangitis (aHR 1.74; p = .003 overall). Steroid-based and mechanistic target of rapamycin inhibitor-based immunosuppression at 1 year post LT were independently associated with increased late OI (p < .001 overall). CONCLUSION: This study found OI hospitalizations to be relatively common among LT recipients and frequently occur later than previously reported. Immunosuppression regimen may be an important modifiable risk factor for late OIs.

Real-world evidence for factors associated with maintenance treatment practices among US adults with autoimmune hepatitis.

BACKGROUND AND AIMS: While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in US patients with AIH. APPROACH AND RESULTS: A retrospective cohort of adults with the incident and prevalent AIH was identified from Optum's deidentified Clinformatics Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic, and with a median age of 61 years. Among 2203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone, and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination and 1.9% monotherapy). Hispanic ethnicity (aOR: 0.56; p = 0.006), cirrhosis (aOR: 0.73; p = 0.019), osteoporosis (aOR: 0.54; p =0.001), and top quintile of provider AIH experience (aOR: 0.66; p = 0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/y; p = 0.004), osteoporosis (+749 mg/y; p < 0.001), and highly experienced providers (+556 mg/y; p < 0.001). CONCLUSIONS: Long-term prednisone therapy remains common and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.

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 to 2021. The utility of the previously defined total SIPAT cutoff (<21 [excellent/good candidates] vs. ≥21 [minimally acceptable/high-risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT scores and LT waitlisting outcomes. The Youden J statistic was used to identify the optimal SIPAT cutoff for patients with MASLD. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had a 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 5-point increase; p = 0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cutoff in this population, resulting in an adjusted OR for a listing of 0.53 versus SIPAT <12 ( p = 0.001). In this large cohort of patients with MASLD evaluated for LT, few patients met the previously defined high SIPAT cutoff for transplant suitability. Nevertheless, increasing the SIPAT score was associated with waitlist outcomes. Our suggested SIPAT cutoff of ≥12 for patients with MASLD warrants further external validation using data from other centers.

Beyond the Granuloma: New Insights into Cardiac Sarcoidosis Using Spatial Proteomics.

Cardiac sarcoidosis is poorly understood, challenging to diagnose, and portends a poor prognosis. A lack of animal models necessitates the use of residual human samples to study sarcoidosis, which in turn necessitates the use of analytical tools compatible with archival, fixed tissue. We employed high-plex spatial protein analysis within a large cohort of archival human cardiac sarcoidosis and control tissue samples, studying the immunologic, fibrotic, and metabolic landscape of sarcoidosis at different stages of disease, in different cardiac tissue compartments, and in tissue regions with and without overt inflammation. Utilizing a small set of differentially expressed protein biomarkers, we also report the development of a predictive model capable of accurately discriminating between control cardiac tissue and sarcoidosis tissue, even when no histologic evidence of sarcoidosis is present. This finding has major translational implications, with the potential to markedly improve the diagnostic yield of clinical biopsies obtained from suspected sarcoidosis patients.

The Potential Utilization of Machine Perfusion to Increase Transplantation of Macrosteatotic Livers.

BACKGROUND: The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP. METHODS: The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival. RESULTS: The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P = 0.235, respectively). CONCLUSIONS: The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

Comparative Effectiveness of Perioperative Antibiotic Regimens to Prevent Surgical Site Infections in Pediatric Liver Transplant Recipients.

BACKGROUND: Surgical site infections (SSIs) are a common complication in liver transplant (LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens. METHODS: We performed a retrospective observational study of LT recipients <18 years old using a merged data set that included data from the Pediatric Health Information System and the United Network for Organ Sharing between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24 hours of LT, with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category in preventing SSI, relative to category 1. RESULTS: Of the 2586 LT, 284 (11%) met SSI criteria. The SSI rate was higher in the younger subcohort (16.2%) than in the older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger subcohort, the adjusted risk was increased in all categories compared with the reference, most notably in category 3 (odds ratio [OR], 2.58 [95% confidence interval: .69-9.59]) and category 6 (2.76 [.66-11.56]). In the older subcohort, estimated ORs were also increased for each category, most notably in category 4 (2.49 [95% confidence interval: .99-6.27]). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E-value assessment suggests that it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective. CONCLUSIONS: There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either subcohort, suggesting that narrower regimens may be adequate.

Living Donor Liver Transplantation for Adults With High Model for End-stage Liver Disease Score: The US Experience.

BACKGROUND: Outcomes after living-donor liver transplantation (LDLT) at high Model for End-stage Liver Disease (MELD) scores are not well characterized in the United States. METHODS: This was a retrospective cohort study using Organ Procurement and Transplantation Network data in adults listed for their first liver transplant alone between 2002 and 2021. Cox proportional hazards models evaluated the association of MELD score (<20, 20-24, 25-29, and ≥30) and patient/graft survival after LDLT and the association of donor type (living versus deceased) on outcomes stratified by MELD. RESULTS: There were 4495 LDLTs included with 5.9% at MELD 25-29 and 1.9% at MELD ≥30. LDLTs at MELD 25-29 and ≥30 LDLT have substantially increased since 2010 and 2015, respectively. Patient survival at MELD ≥30 was not different versus MELD <20: adjusted hazard ratio 1.67 (95% confidence interval, 0.96-2.88). However, graft survival was worse: adjusted hazard ratio (aHR) 1.69 (95% confidence interval, 1.07-2.68). Compared with deceased-donor liver transplant, LDLT led to superior patient survival at MELD <20 (aHR 0.92; P = 0.024) and 20-24 (aHR 0.70; P < 0.001), equivalent patient survival at MELD 25-29 (aHR 0.97; P = 0.843), but worse graft survival at MELD ≥30 (aHR 1.68, P = 0.009). CONCLUSIONS: Although patient survival remains acceptable, the benefits of LDLT may be lost at MELD ≥30.

The Association Between Homelessness and Key Liver-Related Outcomes in Veterans With Cirrhosis.

INTRODUCTION: Homelessness adversely affects patient outcomes in broad cohort studies; however, its impact on key liver-related outcomes in patients with cirrhosis is understudied. We aimed to address this knowledge gap using data from the Veterans Health Administration, a cohort disproportionately affected by homelessness. METHODS: This was a retrospective cohort study of the Veterans Health Administration patients with incident cirrhosis diagnosis between January 2008 and February 2022. Homeless status was classified at baseline and as time-updating variable during follow-up. Inverse probability treatment weighted Cox regression was performed to evaluate the association between homelessness and outcomes of all-cause mortality, cirrhosis decompensation, and hepatocellular carcinoma. RESULTS: A total of 117,698 patients were included in the cohort, of whom 14,243 (12.1%) were homeless at baseline. In inverse probability treatment weighted Cox regression, homelessness was associated with a 24% higher hazard of all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.22-1.26, P < 0.001). However, in competing risk regression models, homelessness was associated with a reduced subhazard of decompensation (subhazard ratio 0.86, 95% CI 0.84-0.88, P < 0.001) and hepatocellular carcinoma (subhazard ratio 0.86, 95% CI 0.83-0.89, P < 0.001). In cause-specific mortality analysis, homeless patients had significantly increased non-liver-related and liver-related mortality; however, the magnitude of effect size was greater for non-liver-related mortality (csHR 1.38, 95% CI 1.35-1.40, P < 0.001). DISCUSSION: Homelessness in veterans with cirrhosis is associated with increased all-cause mortality; however, this is likely mediated primarily through non-liver-related factors. Future studies are needed to explore drivers of mortality and improve mitigation strategies in these patients.