Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

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.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure.

BACKGROUND & AIMS: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). METHODS: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. RESULTS: We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. CONCLUSIONS: The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. IMPACT AND IMPLICATIONS: Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Patients With Acute-on-Chronic Liver Failure Have Greater Healthcare Resource Utilization After Liver Transplantation.

BACKGROUND & AIMS: Although liver transplantation (LT) has been demonstrated to provide survival benefit for patients with acute-on-chronic liver failure (ACLF), data are lacking regarding resource utilization for this population after LT. METHODS: We retrospectively reviewed data from 10 centers in North America of patients transplanted between 2018 and 2019. ACLF was identified by using the European Association for the Study of the Liver-Chronic Liver Failure criteria. RESULTS: We studied 318 patients of whom 106 patients (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Healthcare resource utilization after LT was greater among recipients with ACLF compared with patients without ACLF regarding median post-LT length of hospital stay (LOS) (P < .001), length of post-LT dialysis (P < .001), discharge to a rehabilitation center (P < .001), and 30-day readmission rates (P = .042). Multivariable negative binomial regression analysis demonstrated a significantly longer LOS for patients with ACLF-1 (1.9 days; 95% confidence interval [CI], 0.82-7.51), ACLF-2 (6.7 days; 95% CI, 2.5-24.3), and ACLF-3 (19.3 days; 95% CI, 1.2-39.7), compared with recipients without ACLF. Presence of ACLF-3 at LT was also associated with longer length of dialysis after LT (9.7 days; 95% CI, 4.6-48.8) relative to lower grades. Multivariable logistic regression analysis revealed greater likelihood of discharge to a rehabilitation center among recipients with ACLF-1 (odds ratio [OR], 1.79; 95% CI, 1.09-4.54), ACLF-2 (OR, 2.23; 95% CI, 1.12-5.01), and ACLF-3 (OR, 2.23; 95% CI, 1.40-5.73). Development of bacterial infection after LT also predicted LOS (20.9 days; 95% CI, 6.1-38.5) and 30-day readmissions (OR, 1.39; 95% CI, 1.17-2.25). CONCLUSIONS: Patients with ACLF at LT, particularly ACLF-3, have greater post-transplant healthcare resource utilization.

Practice patterns of the medical evaluation of living liver donors in the United States.

Living donor liver transplantation (LDLT) can help address the growing organ shortage in the United States, yet little is known about the current practice patterns in the medical evaluation of living liver donors. We conducted a 131-question survey of all 53 active LDLT transplant programs in the United States to assess current LDLT practices. The response rate was 100%. Donor acceptance rate was 0.33 with an interquartile range of 0.33-0.54 across all centers. Areas of high intercenter agreement included minimum age cutoff of 18 years (73.6%) and the exclusion of those with greater than Class 1 obesity (body mass index, 30.0-34.9 m/kg 2 ) (88.4%). Diabetes mellitus was not an absolute exclusion at most centers (61.5%). Selective liver biopsies were performed for steatosis or iron overload on imaging (67.9% and 62.3%, respectively) or for elevated liver enzymes (60.4%). Steatohepatitis is considered an exclusion at most centers (84.9%). The most common hypercoagulable tests performed were factor V Leiden (FVL) (88.5%), protein C (73.1%), protein S (71.2%), antithrombin III (71.2%) and prothrombin gene mutation (65.4%). At 41.5% of centers, donors were allowed to proceed with donation with FVL heterozygote status. Most programs discontinue oral contraceptive pills at least 28 days prior to surgery. At most centers, the need for cardiovascular ischemic risk testing is based on age (73.6%) and the presence of one or more cardiac risk factors (68.0%). Defining areas of practice consensus and variation underscores the need for data generation to develop evidence-based guidance for the evaluation and risk assessment of living liver donors.

Gastroesophageal Balloon Tamponade Simulation Training with 3D Printed Model Improves Knowledge, Skill, and Confidence.

BACKGROUND: Gastroesophageal balloon tamponade (BT) tube placement is a life-saving procedure for refractory bleeding from gastroesophageal varices performed by gastroenterologists, intensivists, internists, and emergency medicine physicians. Despite a recognized need for procedural training, no standard curriculum or assessment tools exist. Given the infrequent performance of this procedure, the development of a representative and accessible simulation model would permit hands-on training to practice and maintain proficiency with BT tube placement. AIMS: To assess BT tube placement performance before and after a novel simulation-based learning module in gastroenterology fellows and faculty. METHODS: A 16-item knowledge questionnaire and 22-item procedural skill checklist utilizing a novel 3D printed esophagus model were developed to assess participant knowledge, procedural skills, and confidence prior to our simulation-based intervention and again 8-12 weeks after. Performance metrics were compared pre- and post-intervention within groups and between participant groups. RESULTS: Fifteen gastroenterology fellows (of 15 eligible; 100%) and 14 gastroenterology faculty (of 29 eligible; 48%) completed training. Fellows demonstrated improvement in knowledge (55% to 79%, p < 0.001) and procedural skill (35% to 57%, p < 0.001) following training. Baseline faculty performance did not differ from fellows' performance and post-intervention showed similar improvement in knowledge (61% to 77%, p = 0.001) and procedural skill (40% to 49%, p = 0.147). Overall satisfaction with training was high in both groups post-intervention and faculty felt more confident teaching fellows. CONCLUSION: The presented learning module offers a unique, low stakes opportunity for learners to improve skills, gain knowledge, and build confidence in placing BT tubes using a realistic simulation model.

Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

Heterogeneity in Center Practices in Liver Transplantation for Alcohol-Associated Liver Disease in the United States.

INTRODUCTION: Alcohol-related liver disease (ALD) is now the leading indication for liver transplantation (LT) in the United States (US). It remains unclear how centers are managing the medical and psychosocial issues associated with these patients. METHODS: We conducted a web-based survey of LT centers in the United States to identify center-level details on peri-LT management of ALD and related issues. RESULTS: Of the 117 adult LT centers, 100 responses (85.5%) were collected, representing all Organ Procurement and Transplantation Network regions. For alcohol-associated cirrhosis, 70.0% of the centers reported no minimum sobriety requirement while 21.0% required 6 months of sobriety. LT for severe alcohol-associated hepatitis was performed at 85.0% of the centers. Monitoring protocols for pre-LT and post-LT alcohol use varied among centers. DISCUSSION: Our findings highlight a change in center attitudes toward LT for ALD, particularly for severe alcohol-associated hepatitis.

Burnout Among Transplant Hepatologists in the United States.

Burnout among transplant hepatologists has not been well characterized. The goal of this study was to describe the prevalence and predictors of burnout among practicing transplant hepatologists in the United States. We designed a 69-item survey, including the Maslach Burnout Inventory (MBI)-Human Services Survey and questions on provider demographics, practice characteristics, and psychological factors. The survey was administered to practicing US transplant hepatologists between October and December 2019. We described burnout using MBI subscales (emotional exhaustion [EE], depersonalization [DP], and personal accomplishment [PA]) and determined significant predictors of burnout, which we defined as high EE, using univariate and multivariate analyses. A total of 185 transplant hepatologists completed the survey (response rate = 25% of 738 practicing transplant hepatologists in the United States). A total of 40% reported high EE, whereas 17% and 16% reported high DP and low PA, respectively. On multivariate analysis, respondents with more than 5 colleagues (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.84) reporting adequate time for outpatient visits (OR, 0.42; 95% CI, 0.22-0.80), reporting greater comfort with their clinical caseload (OR, 0.61; 95% CI, 0.39-0.96), and reporting higher confidence in their prior training (OR, 0.49; 95% CI, 0.28-0.87) had a lower likelihood of high EE. Working 6 or more hours from home outside of work per week (OR, 2.04; 95% CI, 1.07-3.89) predicted a higher likelihood of burnout. Compensation, age, gender, career phase, caregiver status, and transplant center volume did not predict burnout. Of the surveyed transplant hepatologists, 40% experienced burnout, predicted mostly by factors related to work-time distribution, peer support, and affect. These findings should prompt development of system-level initiatives.

Coagulopathy and hemostasis management in patients undergoing liver transplantation: Defining a dynamic spectrum across phases of care.

Patients with acute and chronic liver disease present with a wide range of disease states and severity that may require liver transplantation (LT). Physiologic alterations occur that are dynamic throughout all phases of perioperative care, creating complex management scenarios that necessitate multidisciplinary clinical care. Specifically, alterations in hemostasis in liver disease can be pronounced and evolve with disease progression over time. Recent studies and society guidance address this emerging paradigm and offer recommendations to assist with hemostatic management in patients with liver disease. However, patients undergoing LT are unique and diverse, often with unstable disease that requires specialized approaches. Our aim is to provide a focused review of hemostatic management of the LT patient, distinguish unique aspects of the three main phases of care (before LT, perioperative, and after LT), and identify knowledge gaps and critical areas of future research.

Risk Factors for Posttransplantation Mortality in Recipients With Grade 3 Acute-on-Chronic Liver Failure: Analysis of a North American Consortium.

Although liver transplantation (LT) yields survival benefit for patients with acute-on-chronic liver failure grade 3 (ACLF-3), knowledge gaps remain regarding risk factors for post-LT mortality. We retrospectively reviewed data from 10 centers in the United States and Canada for patients transplanted between 2018 and 2019 and who required care in the intensive care unit prior to LT. ACLF was identified using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. A total of 318 patients were studied, of whom 106 (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Survival probability 1 year after LT was significantly higher in patients without ACLF (94.3%) compared with patients with ACLF (87.3%; P = 0.02), but similar between ACLF-1 (88.5%), ACLF-2 (87.8%), and ACLF-3 (85.7%; P = 0.26). Recipients with ACLF-3 and circulatory failure (n = 29) had similar 1-year post-LT survival (82.3%) compared with patients with ACLF-3 without circulatory failure (89.6%; P = 0.32), including those requiring multiple vasopressors. For patients transplanted with ACLF-3 including respiratory failure (n = 20), there was a trend toward significantly lower post-LT survival (P =  0.07) among those with respiratory failure (74.1%) compared with those without (91.0%). The presence of portal vein thrombosis (PVT) at LT for patients with ACLF-3 (n = 15), however, yielded significantly lower survival (91.9% versus 57.1%; P < 0.001). Multivariable logistic regression analysis revealed that PVT was significantly associated with post-LT mortality within 1 year (odds ratio, 7.3; 95% confidence interval, 1.9-28.3). No correlation was found between survival after LT and the location or extent of PVT, presence of transjugular intrahepatic portosystemic shunt, or anticoagulation. LT in patients with ACLF-3 requiring vasopressors yields excellent 1-year survival. LT should be approached cautiously among candidates with ACLF-3 and PVT.

Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.

Ethnoracial Disparity in Hospital Survival following Transjugular Intrahepatic Portosystemic Shunt Creation for Acute Variceal Bleeding in the United States.

PURPOSE: To investigate the magnitude of racial/ethnic differences in hospital mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding and whether hospital care processes contribute to them. METHODS: Patients aged ≥18 years undergoing TIPS creation for acute variceal bleeding in the United States (n = 10,331) were identified from 10 years (2007-2016) available in the National Inpatient Sample. Hierarchical logistic regression was used to examine the relationship between patient race and inpatient mortality, controlling for disease severity, treatment utilization, and hospital characteristics. RESULTS: A total of 6,350 (62%) patients were White, 1,780 (17%) were Hispanic, and 482 (5%) were Black. A greater proportion of Black patients were admitted to urban teaching hospitals (Black, n = 409 (85%); Hispanic, n = 1,310 (74%); and White, n = 4,802 (76%); P < .001) and liver transplant centers (Black, n = 215 (45%); Hispanic, n = 401 (23%); and White, n = 2,267 (36%); P < .001). Being Black was strongly associated with mortality (Black, 32% vs non-Black, 15%; odds ratio, 3.0 [95% confidence interval, 1.6-5.8]; P = .001), as assessed using the risk-adjusted regression model. This racial disparity disappeared in a sensitivity analysis including only patients with a maximum Child-Pugh score of 13 (odds ratio 1.2 [95% confidence interval, 0.4-3.6]; P = .68), performed to compensate for the absence of Model for End-stage Liver Disease scores. Ethnoracial differences in access to teaching hospitals, liver transplant centers, first-line endoscopy, and transfusion did not significantly contribute (P > .05) to risk-adjusted mortality. CONCLUSIONS: Black patients have a 2-fold higher inpatient mortality than non-Black patients following TIPS creation for acute variceal bleeding, possibly related to greater disease severity before the procedure.

Evaluation and selection of the liver transplant candidate: updates on a dynamic and evolving process.

PURPOSE OF REVIEW: Although conceptually unchanged, the evaluation and selection of the liver transplant candidate has seen significant recent advances. Expanding criteria for transplant candidacy, improved diagnostics for risk stratification and advances in prognostic models have paralleled recent changes in allocation and distribution that require us to revisit core concepts of candidate evaluation and selection while recognizing its now dynamic and continuous nature. RECENT FINDINGS: The liver transplant evaluation revolves around three interrelated themes: candidate selection, donor selection and transplant outcome. Introduction of dynamic frailty indices, bariatric surgery at the time of liver transplant in obese patients and improved therapies and prognostic tools for hepatobiliary malignancy have transformed candidate selection. Advances in hypothermic organ preservation have improved outcomes in marginal donor organs. Combined with expansion of hepatitis C virus positive and split donor organs, donor selection has become an integral part of candidate evaluation. In addition, with liver transplant for acute alcohol-related hepatitis now widely performed and increasing recognition of acute-on-chronic liver failure, selection of critically ill patients is refining tools to balance futility versus utility. SUMMARY: Advances in liver transplant candidate evaluation continue to transform the evaluation process and require continued incorporation into our clinical practice amidst a dynamic backdrop of demographic and policy changes.

Longterm Outcomes of Patients Undergoing Liver Transplantation for Acute-on-Chronic Liver Failure.

Recent data have demonstrated >80% 1-year survival probability after liver transplantation (LT) for patients with severe acute-on-chronic liver failure (ACLF). However, longterm outcomes and complications are still unknown for this population. Our aim was to compare longterm patient and graft survival among patients transplanted across all grades of ACLF. We analyzed the United Network for Organ Sharing database for the years 2004-2017. Patients with ACLF were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Kaplan-Meier and Cox regression methods were used to determine patient and graft survival and associated predictors of mortality in adjusted models. A total of 56,801 patients underwent transplantation of which 31,024 (54.6%) had no ACLF, 8757 (15.4%) had ACLF grade 1, 9039 (15.9%) had ACLF grade 2, and 7891 (14.1%) had ACLF grade 3. The 5-year patient survival after LT was lower in the ACLF grade 3 patients compared with the other groups (67.7%; P < 0.001), although after year 1, the percentage decrease in survival was similar among all groups. Infection was the primary cause of death among all patient groups in the first year. Infection was the primary cause of death among all patient groups in the first year. After the first year, infection was the main cause of death in patients transplanted with ACLF grade 1 (32.1%), ACLF grade 2 (33.9%), and ACLF grade 3 (37.6%), whereas malignancy was the predominant cause of death in those transplanted with no ACLF (28.5%). In conclusion, patients transplanted with ACLF grade 3 had lower 5-year survival as compared with patients with ACLF grades 0-2, but mortality rates were not significantly different after the first year following LT. Graft survival was excellent across all ACLF groups.

Presence of any degree of coronary artery disease among liver transplant candidates is associated with increased rate of post-transplant major adverse cardiac events.

The impact of coronary artery disease (CAD) among liver transplant candidates (LTC) on post-LT clinical outcomes remains unclear. The aim of this study is to determine association of presence and severity of CAD on post-LT major adverse cardiac events (MACE) including cardiac-associated mortality. We conducted a retrospective cohort analysis of 231 patients who underwent diagnostic coronary angiogram (DCA) during their LT evaluation at a tertiary medical center from 2012-2017. Patients were analyzed based on degree of CAD (no CAD, non-obstructive CAD [< 50% stenosis], obstructive CAD [≥50% stenosis]) per DCA results. MACE were noted at 30 days, 1 year, 3 years, and 5 years post-LT, and Kaplan-Meier curves were used to determine post-LT MACE-free probability. LTC with any CAD, including non-obstructive CAD, had lower MACE-free probability at all post-LT time points (0.94 vs 0.65 at 30 days, P = .001; 0.87 vs 0.59 at 1 year, P = .002; 0.87 vs 0.41 at 3 years, P < .001; 0.87 vs 0.37 at 5 years, P < .001). Identification of and medical intervention for non-obstructive CAD should be considered in all LTC, though further studies are necessary to determine optimal medical interventions to mitigate MACE risk in this cohort.