End-stage Liver Disease Patients Research Articles

Cardiovascular disease assessment and management in liver transplantation.

The prevalence and mortality related to end-stage liver disease (ESLD) continue to rise globally. Liver transplant (LT) recipients continue to be older and have inherently more comorbidities. Among these, cardiac disease is one of the three main causes of morbidity and mortality after LT. Several reasons exist including the high prevalence of associated risk factors, which can also be attributed to the rise in the proportion of patients undergoing LT for metabolic dysfunction-associated steatohepatitis (MASH). Additionally, as people age, the prevalence of now treatable cardiac conditions, including coronary artery disease (CAD), cardiomyopathies, significant valvular heart disease, pulmonary hypertension, and arrhythmias rises, making the need to treat these conditions critical to optimize outcomes. There is an emerging body of literature regarding CAD screening in patients with ESLD, however, there is a paucity of strong evidence to support the guidance regarding the management of cardiac conditions in the pre-LT and perioperative settings. This has resulted in significant variations in assessment strategies and clinical management of cardiac disease in LT candidates between transplant centres, which impacts LT candidacy based on a transplant centre's risk tolerance and comfort level for caring for patients with concomitant cardiac disease. Performing a comprehensive assessment and understanding the potential approaches to the management of ESLD patients with cardiac conditions may increase the acceptance of patients, who appear too complex, but rather require extra evaluation and may be reasonable candidates for LT. The unique physiology of ESLD can profoundly influence preoperative assessment, perioperative management, and outcomes associated with underlying cardiac pathology, and requires a thoughtful multidisciplinary approach. The strategies proposed in this manuscript attempt to review the latest expert experience and opinions and provide guidance to practicing clinicians who assess and treat patients being considered for LT. These topics also highlight the gaps that exist in the comprehensive care of LT patients and the need for future investigations in this field.

Living Donor Availability Improves Patient Survival in a North American Center: An Intention-to-treat Analysis.

Assess the impact of having a living donor on waitlist outcomes and overall survival through an intention-to-treat analysis. Living-donor liver transplantation (LDLT) offers an alternative to deceased donation in the face of organ shortage. An as-treated analysis revealed that undergoing LDLT, compared to staying on the waiting list, is associated with improved survival, even at Model for End-stage Liver Disease-sodium (MELD-Na) score of 11. Liver transplant candidates listed at the Ajmera Transplant Centre (2000-2021) were categorized as pLDLT (having a potential living donor) or pDDLT (without a living donor). Employing Cox proportional-hazard regression with time-dependent covariates, we evaluated pLDLT's impact on waitlist dropout and overall survival through a risk-adjusted analysis. Of 4,124 candidates, 984 (24%) had potential living donors. The pLDLT group experienced significantly lower overall waitlist dropouts (5.2%vs. 34.4%, P<0.001) and mortality (3.8%vs. 24.4%, P<0.001) compared to the pDDLT group. Possessing a living donor correlated with a 26% decline in the risk of waitlist dropout (adjusted hazard ratio 0.74, 95%CI 0.55-0.99, P=0.042). The pLDLT group also demonstrated superior survival outcomes at 1- (84.9%vs. 80.1%), 5- (77.6%vs. 61.7%), and 10-year (65.6%vs.52.9%) from listing (log-rank P<0.001) with a 35% reduced risk of death (adjusted hazard ratio 0.65, 95%CI 0.56-0.76, P<0.001). Moreover, the predicted hazard ratios consistently remained below 1 across the MELD-Na range 11-26. Having a potential living donor significantly improves survival in end-stage liver disease patients, even with MELD-Na scores as low as 11. This emphasizes the need to promote awareness and adoption of LDLT in liver transplant programs worldwide.

Impact of Pre- and Post-therapeutic Exercises in Sarcopenia and Pain in Liver Transplant Patients.

Sarcopenia, a state considered by the loss of muscle function and mass, is progressively recognized as a common complication of advanced cirrhosis and is related to negative clinical consequences. Liver transplantation (LT) is one of the options in the treatment of cirrhosis. This study aimed to evaluate the impact of exercise in newly developed (ND) sarcopenia through measurement of the psoas major muscle at the level of the third lumbar vertebra by abdominal computed tomography (CT) images in liver transplant patients. This analytical case-control longitudinal study was conducted on patients aged between 16 and 70 years at King Fahad Specialist Hospital (KFSH-D) in Dammam, Saudi Arabia. The patients were divided into two groups:an intervention group consisting of liver transplant patients (LTx, n=26) and a control group consisting of end-stage liver disease patients (ESLD, n=23) who were not candidates for LT. All participants were treated with a therapeutic exercise program through three phases. The first phase included pre-operative exercises, the second phase included early post-operative exercises, and the last phase included late post-operative exercises. CT scan of the psoas major muscle was performed pre- and post-LT to assess sarcopenia. Pain was measured with a numerical pain scale before and after exercise to evaluate the impact of exercise on pain. Psoas muscle index (PMI) for post-therapeutic exercises in the control and liver transplant groups showed significant differences for both male and female patients compared with the normal range (p<0.05). The liver transplant group showed a significant difference in mean weight loss, body mass index (BMI), and numerical pain rating scale (NPRS) observed on post-therapeutic exercises compared to baseline data. Conclusion: By and large, the finding revealed a substantial impact of therapeutic exercise on patient outcomes in terms of anthropometric characteristics, abdominal pain, handgrip strength (HGS), and PMI. The mean PMI at post-therapeutic exercises showed a significant increase by measuring the psoas major muscle at the level of the third lumbar vertebra by abdominal CT, which may indicate the extent of improvement and recovery from the ND sarcopenia in LTx.The results emphasize the potential advantages of pre- and post-therapeutic exercise in LTx, including enhancements in muscle strength and mass, as well as pain management associated with liver function and general health. Optimizing patient outcomes and promoting a more comprehensive approach to liver disease treatment may be achieved by including exercise activities in pre- and post-LT care procedures.

How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach.

Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients. To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT. A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ²-test. In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis (n = 1) and pulmonary infections (n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality (n = 1), postoperative pulmonary infections (n = 8), abdominal infection (n = 1), hepatic artery thromboses (n = 3), portal vein thrombosis (n = 1), and intra-abdominal bleeding (n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups (P > 0.05). Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers.

Clinical Characteristics and Outcomes Associated With Distinct Hemodynamic Patterns in End-stage Liver Disease: A Retrospective Cohort Analysis

IntroductionDespite advances in the diagnosis and therapeutics strategies for pulmonary hypertension (PH) in patients with end-stage liver disease (ESLD), the impact of hemodynamic patterns among ESLD patients identified through right heart catheterization (RHC) on clinical outcomes remains poorly understood. MethodsThis single-center retrospective cohort study identified patients diagnosed with ESLD who underwent RHC from August 2018 to June 2023. Demographic and clinical data, including comorbidities, transthoracic echocardiography, and RHC findings, were obtained. Our outcomes of interest were all-cause mortality and the chance of receiving orthotopic liver transplantation (OLT) within a year after RHC. Kaplan-Meier with log-rank test was employed to generate survival curves. ResultsWe identified 415 ESLD patients with the RHC results. The median (IQR) age was 59 years (52-66), and 62% were male. Caucasians accounted for 43%, followed by African Americans (30%). Up to 89% had a diagnosis of portal hypertension. Median MELD-Na score was 30 (19-36). The etiology of ESLD was mainly from alcohol use (55%). Patients were classified based on RHC results as pre-capillary PH (19%), post-capillary PH (28%), and non-PH (53%) groups. Overall, one-year mortality post-RHC was 22%, with no significant difference in mortality regardless of hemodynamic group. However, the pre-capillary PH group was less likely to receive OLT compared to other groups (p<0.001). ConclusionWe observed no difference in all-cause mortality among hemodynamic groups. However, pre-capillary PH group were less likely to undergo OLT compared to others. Further investigations are necessary to determine how this should be addressed in clinical practice.

Microbiological and molecular studies on a multidrug-resistant Pseudomonas aeruginosa from a liver transplant patient with urinary tract infection in Egypt.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for complicated UTIs and exhibits high antibiotic resistance, leading to increased mortality rates, especially in cases of multidrug-resistant strains. This study aimed to investigate the antibiotic susceptibility patterns and genomic characterization of XDR strains identified in end-stage liver disease patients who underwent liver transplants. In this study, a number of 30 individuals who underwent liver transplants were registered. Ninety urine and 60 wound site swab samples were collected and processed for culturing, identification, and antimicrobial sensitivity. Extensively drug-resistant strain EMARA01 was confirmed through Sanger sequencing and was then processed for whole genome sequencing to characterize the genomic pattern. Sequencing data were processed for de novo assembly using various tools and databases, including genome annotation, serotype identification, virulence factor genes, and antimicrobial resistance gene. Pangenome analysis of randomly selected 147 reference strains and EMAR01 sequenced strain was performed using the Bacterial Pan Genome Analysis (BPGA) software. Of these total examined samples, nosocomial infection due to P. aeruginosa was detected in twelve patients' samples. AST analysis showed that P. aeruginosa strains exhibit resistance to tobramycin, erythromycin, and gentamicin, followed by piperacillin and ofloxacin, and no strains exhibit resistance to meropenem and imipenem. The CARD database identified 59 AMR genes similar to the EMAR01 strain genome and mostly belong to the family involved in the resistance-nodulation-cell division (RND) antibiotic efflux pump. Five genes; nalC, nalD, MexR, MexA, and MexB, exhibit resistance to 14 classes of antibiotics, while two AMR; CpxR, and OprM, exhibit resistance to 15 classes of drugs. Pangenome analysis revealed that the pan-genome remained open, suggesting the potential for acquiring accessory and unique genes. Notably, the genes predominantly involved in amino acid transport metabolism were identified using the KEGG database. This study provides valuable insights into the antimicrobial resistance profile, genetic features, and genomic evolution of P. aeruginosa strains causing UTIs in liver transplant patients. The findings emphasize the significance of comprehending AMR mechanisms and genetic diversity in P. aeruginosa for developing effective treatment strategies and infection control measures.

Beyond the Diagnosis: A Deep Dive Into the End Stage Liver Disease Experience From the Patient Perspective.

End-stage liver disease (ESLD) presents a multifaceted challenge that encompasses not only physical but also emotional, psychological, and social dimensions. This study aims to explore the experiences of ESLD patients within the United States healthcare system. Utilizing a convenience sampling methodology, 15 ESLD patients from a tertiary care hospital in the USA participated in semi-structured interviews between April 2023 and January 2024. Data analysis was conducted using MAXQDA 2023, employing a phenomenological approach to identify common themes. The study identified six primary themes: the significance of communication style in diagnosis delivery, the crucial role of family and social support, varied understanding and preferences for palliative care, diverse attitudes towards advanced care planning, preferences for coordinated healthcare experiences, and the emotional and psychological impact of ESLD. Our study underscores the complexity of ESLD patient care beyond medical treatment, highlighting the importance of clear communication, empathetic care, and the integration of family and palliative care services.

ADVANCED CARDIAC IMAGING IN LIVER TRANSPLANTATION ECHOCARDIOGRAPHIC VENTRICULAR STRAIN AS PROGNOSTIC TOOLS

Abstract While cardiac involvement in the end–stage liver disease (ESLD) is a known condition, the characteristics of cardiac function in cirrhotic cardiomyopathy and their effects on candidates to liver transplant (LT) are still vague. The evaluation of right ventricular failure (RVF) in liver transplant candidates has been revolutionized by advanced cardiac imaging techniques, particularly echocardiography with global longitudinal strain (GLS) analysis. Aim of the present study is to evaluate RV function indexes in ESLD patients candidate to LT and the potential relationship with the liver disease status and cardiovascular major events on early post–LT phase Forty ESDL adult patients (age 46.8 ± 10 yrs, M/F 33/7) candidate to LT (19 for hepatic failure, 18 for hepatocarcinoma and 3 for other causes) were evaluate. All were submitted to transthoracic echocardiography and coronary CT angiography or coronary angiography. The Model for End–stage Liver Disease (MELD) score in the study population was 19±6.8. The higher values of the MELD score (i.e. the worst liver function condition) were directly correlated with the lower RV–GLS (p&amp;lt;0.02). Cardiac function indexes were LV–EF 62.8±4.5%, RV–GLS –22.9±4.5%, LV–GLS –19.5±4.6% and PAPs 31.8±6.6 mmHg. On 21 day follow–up, 4 patients died (2 with acute RV failure, 1 with Tako–Tsubo syndrome). On CT–angiography the value of calcium score was significantly different between the group of fatal events and the rest (0 vs 567±900), revealing that none of the died patient suffered from coronary atheromatic disease. Our findings identified that specific RV–GLS patterns on echocardiography, indicative of subclinical myocardial dysfunction, were strongly correlated with worst clinical hepatic conditions and reduced survival rates post–transplant. The study highlights the importance of advanced cardiac imaging in identifying liver transplant candidates at higher risk of post–transplant mortality due to RHF.

Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.

Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools. EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform. Different-sized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p, miR-28-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-429, were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT. These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease: A meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) is commonly utilized as a prognostic indicator in end-stage liver disease (ESLD), encompassing conditions like liver failure and decompensated cirrhosis. Nevertheless, some studies have contested the prognostic value of NLR in ESLD. To investigate the ability of NLR to predict ESLD. Databases, such as Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang, were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD. Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1. A total of thirty studies involving patients with end-stage liver disease (ESLD) were included in the evaluation. Among the pooled results of eight studies, it was observed that the Neutrophil-to-Lymphocyte Ratio (NLR) was significantly higher in non-survivors compared to survivors (random-effects model: standardized mean difference = 1.02, 95% confidence interval = 0.67-1.37). Additionally, twenty-seven studies examined the associations between NLR and mortality in ESLD patients, reporting either hazard ratios (HR) or odds ratios (OR). The combined findings indicated a link between NLR and ESLD mortality (random-effects model; univariate HR = 1.07, 95%CI = 1.05-1.09; multivariate HR = 1.07, 95%CI = 1.07-1.09; univariate OR = 1.29, 95%CI = 1.18-1.39; multivariate OR = 1.29, 95%CI = 1.09-1.49). Furthermore, subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality, with Asian studies demonstrating a more pronounced effect. Increased NLR in patients with ESLD is associated with a higher risk of mortality, particularly in Asian patients. NLR is a useful prognostic biomarker in patients with ESLD.

Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women.

Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort. We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis. During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P < 0.001) than White women and non-White male patients (26.1 versus 24.8; P < 0.001). Graft and patient survivals were significantly different ( P < 0.001) between non-White women and White women and men (White and non-White). Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.

Risk factors for short-term prognosis of end-stage liver disease complicated by invasive pulmonary aspergillosis.

Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.

Performance of risk prediction models for post-liver transplant patient and graft survival over time.

Given liver transplantation organ scarcity, selection of recipients and donors to maximize post-transplant benefit is paramount. Several scores predict post-transplant outcomes by isolating elements of donor and recipient risk, including the donor risk index, Balance of Risk, pre-allocation score to predict survival outcomes following liver transplantation/survival outcomes following liver transplantation (SOFT), improved donor-to-recipient allocation score for deceased donors only/improved donor-to-recipient allocation score for both deceased and living donors (ID2EAL-D/-DR), and survival benefit (SB) models. No studies have examined the performance of these models over time, which is critical in an ever-evolving transplant landscape. This was a retrospective cohort study of liver transplantation events in the UNOS database from 2002 to 2021. We used Cox regression to evaluate model discrimination (Harrell's C) and calibration (testing of calibration curves) for post-transplant patient and graft survival at specified post-transplant timepoints. Sub-analyses were performed in the modern transplant era (post-2014) and for key donor-recipient characteristics. A total of 112,357 transplants were included. The SB and SOFT scores had the highest discrimination for short-term patient and graft survival, including in the modern transplant era, where only the SB model had good discrimination (C ≥ 0.60) for all patient and graft outcome timepoints. However, these models had evidence of poor calibration at 3- and 5-year patient survival timepoints. The ID2EAL-DR score had lower discrimination but adequate calibration at all patient survival timepoints. In stratified analyses, SB and SOFT scores performed better in younger (< 40 y) and higher Model for End-Stage Liver Disease (≥ 25) patients. All prediction scores had declining discrimination over time, and scores relying on donor factors alone had poor performance. Although the SB and SOFT scores had the best overall performance, all models demonstrated declining performance over time. This underscores the importance of periodically updating and/or developing new prediction models to reflect the evolving transplant field. Scores relying on donor factors alone do not meaningfully inform post-transplant risk.

National frequency, trends, and healthcare burden of care fragmentation in readmissions for end-stage liver disease in the USA.

End-stage liver disease (ESLD) patients have frequent readmissions to the same facility or a different hospital (care fragmentation). Care fragmentation results in care delivery from an unfamiliar clinical team or setting, a potential source of suboptimal clinical outcomes. We examined the occurrence, trends, and association between care fragmentation and outcomes during readmissions for ESLD. From the Nationwide Readmissions Database (January to September 2010-2014), we followed adult (age ≥18 years) hospitalizations for ESLD who were discharged alive for 90 days. During 30- and 90-day readmissions, we calculated the frequency, determinants, and clinical outcomes of care fragmentation (SAS 9.4). Of the 67,480 ESLD hospitalizations surviving at discharge from 2010-2014, 35% (23,872) and 52% (35,549) were readmitted in 30- and 90-days respectively. During readmissions, the frequencies of care fragmentation were similar (30-day: 25.4% and 90-day: 25.8%) and remained stable from 2010 to 2014 (P trends>0.5). Similarly, factors associated with care fragmentation were consistent across 30- and 90-day readmissions. These included ages: 18-44 years, liver cancer, receipt of liver transplantation, hepatorenal syndrome, prolonged length of stay, and hospitalization in non-teaching facilities. During 30- and 90-day readmissions, care fragmentation was associated with higher risk of mortality (adjusted mean ratio: 1.13[1.03-1.24] and 1.14 [1.06-1.23]; P values<0.0001), prolonged length of stay (4.6-days vs. 4.1-days and 5.2-days vs. 4.6-days; P values<0.0001), and higher hospital charges ($36,884 vs. $28,932 and $37,354 vs. $30,851; P values<0.0001). Care fragmentation is high among readmissions for ESLD and is associated with poorer outcomes.

Gut microbiota dynamics in a 1-year follow-up after adult liver transplantation in Northeast China.

Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China. Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways. Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation. Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.

Simultaneous split liver/kidney transplantation: A national and single center experience report.

End-stage liver disease (ESLD) and end-stage renal disease (ESRD) are prevalent diseases for which the definitive treatment is transplantation. With limited organ supply, strategies to maximize organ availability has led to increasing rates of split liver transplantations for ESLD patients. Therefore, simultaneous split liver and kidney transplantations (SSLK) for patients with ESLD and ESRD could represent a treatment option for comorbid patients. However, current practice and outcomes after SSLK are unknown. We aim to report national trends and our experience with patients undergoing SSLK. We performed a retrospective review of the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research file from January 2011-April 2022. Descriptive analysis of preoperative characteristics, postoperative outcomes and actuarial graft and patient survivals are reported. National review of the UNOS transplant registry from 2011-2021 of adult patients undergoing initial transplantation via SSLK demonstrates that this procedure remains uncommon, with only 76 such cases captured in that time. Nevertheless, survival rates at 1, 3, and 5 years remains robust, at 94%, 92%, and 90% for patients overall, 90%, 88%, 88%, for the liver graft, and 93%, 91%, 88% for the kidney graft, respectively. Review of a single center experience with three such patients from 2019-2021 has shown a safe, enduring transplant option with no graft complications seen. SSLK is both safe and a feasible option to optimize organ supply while allowing recipients to receive quality liver and kidney grafts and should be considered more often by transplant centers going forward.

2734. Evaluation of Empiric Antimicrobial Therapy for End-Stage Liver Disease Patients at an Academic Medical Center

Abstract Background Patients with end-stage liver disease (ESLD) are prone to decompensation secondary to infections, with an increasing prevalence of multidrug-resistant organisms (MDROs). These patients often receive broad-spectrum antimicrobials prior to transplant, pre-disposing them to resistant pathogens. Our study assessed institutional guideline adherence, antimicrobial prescribing, and the incidence of MDROs in this population. Methods This IRB-approved, retrospective chart review included pre-transplant inpatients with ESLD on the adult liver transplant service who received antimicrobials between 1/1/20 and 10/30/20. Patients were excluded if they started antimicrobials post-transplant or transferred from another institution on parenteral antimicrobials. Per institutional guidelines for empiric antimicrobials in suspected infection in ESLD, patients were categorized into three infectious risk categories: Floor/Non-High-Risk (F-NHR), Floor/High-Risk (F-HR), and ICU or MELD greater than 35 (ICU/M35). Antimicrobial prescribing in each group was evaluated for guideline adherence and microbiology data. Results were analyzed using descriptive statistics. Results We included 92 patients: 28 F-NHR, 50 F-HR, and 14 ICU/M35. Table 1 summarizes baseline characteristics. The frequency of guideline adherence for the F-NHR, F-HR, ICU/M35 groups, respectively, was 11 (39%), 4 (8%), and 4 (29%) patients. For the F-NHR group, ceftriaxone (CRO) was most prescribed (n=17, 61%). For the F-HR group, 18 (36%) received CRO; 16 (32%) received vancomycin and piperacillin-tazobactam. In the ICU/M35 group, 13 patients (93%) received meropenem plus linezolid, and 11 (79%) also received caspofungin. No methicillin-resistant Staphylococcus aureus or carbapenem-resistant Enterobacterales were isolated. Two patients (14%) in the ICU/M35 group experienced C. difficile infection within 30 days of antimicrobial initiation.Table 1.Baseline characteristics among guideline cohorts Conclusion Our study showcases opportunities to optimize internal ESLD antimicrobial protocols and curtail unnecessary antimicrobial exposure. Study limitations include a small cohort at a single center. Future directions include data dissemination and protocol updates. Disclosures David Quan, PharmD, Mallinckrodt Pharmaceuticals: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea: Clinical events committee/adjudication committee participation|F2G: Grant/Research Support|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clinical events committee/adjudication committee participation

Early palliative care referral may improve end-of-life care in end-stage liver disease patients: A retrospective analysis from a non-transplant center

BackgroundPatients with end-stage liver disease (ESLD) who are not transplant candidates often have a trajectory of rapid decline and death similar to patients with stage IV cancer. Palliative care (PC) services have been shown to be underutilized for such patients. Most studies examining the role of PC in ESLD have been done at transplant centers. Thus, determining the utilization and benefit of PC at a non-transplant tertiary center may help establish a standard of care in the management of patients with ESLD not eligible for transplant. MethodsWe conducted a retrospective analysis of adult (>18 years) patients with ESLD admitted to Rochester Regional Health (RRH) system hospitals from 2012 to 2021. Patients were divided into groups based on the presence or absence of PC involvement. Baseline characteristics were recorded. The impact of PC was assessed by comparing the number of hospitalizations before and after the involvement of PC, comparing code status changes, health care proxy (HCP) assignments, Aspira catheter placements, and frequency of repeated paracentesis. ResultsIn our analysis of 576 patients, 41.1% (237 patients) received a PC consult (PC group), while 58.9% (339 patients) did not (no-PC group). Baseline characteristics were comparable.However, their mean number of admissions significantly decreased (15.66 vs. 3.49, p < 0.001) after PC involvement. Full code status was more prevalent in the no-PC group (67.8% vs. 18.6%, p < 0.001), while comfort care code status was more common in the PC group (59.9% vs. 20.6%, p < 0.001). Changes in code status were significantly higher in the PC group (77.6% vs. 29.2%, p < 0.001). The PC group had a significantly higher mortality rate (83.1% vs. 46.4%, p < 0.01). Patients in the PC group had a higher likelihood of having an assigned HCP (63.7% vs. 37.5%, p < 0.001). PC referral was associated with more frequent use of an Aspira catheter (5.9% vs. 0.9%, p < 0.001) and more frequent paracentesis (30.8% vs. 16.8%, p < 0.001). ConclusionsIn conclusion, our study provides compelling evidence of the diverse advantages of palliative care for patients with end-stage liver disease, including reduced admissions, improved goals of care, code status modifications, enhanced healthcare proxy assignments, and targeted interventions. These findings highlight the potential significance of early integration of palliative care in the disease trajectory to provide comprehensive, patient-centered care that addresses the unique needs and preferences of individuals with advanced liver disease.

Recent Trends in Palliative Care Utilization in Patients With Decompensated Liver Disease: 2016-2020 National Analysis.

Background: Patients with end-stage liver disease (ESLD) have a poor quality of life, which often worsens as disease severity increases. Palliative care (PC) has emerged as a management option in ESLD patients, especially for those who are not candidates for a liver transplant. Objective: To assess the associated factors and trends in PC utilization in recent years. Design: We used the 2016-2020 National Inpatient Sample (NIS) database of the United States to identify patients with decompensated cirrhosis who suffered in-hospital mortality. Information regarding patient demographics, hospital characteristics, etiology and decompensations, Elixhauser comorbidities, and interventions was collected. The multivariate regression model was used to identify factors associated with PC use. Results: Out of 98,160 patients, 52,645 patients (53.6%) received PC consultations. PC utilization increased from 49.11% in 2016 to 56.85% in 2019, with a slight decrease to 54.47% in 2020. Patients with PC use had decreased incidence of blood transfusions (28.85% vs. 36.53%, p < 0.001), endoscopy (18% vs. 20.26%, p 0.0001), liver transplantation (0.28% vs. 0.69%, p < 0.001), and mechanical ventilation (46.22% vs. 56.37%, p < 0.001). African American, Hispanic, and Asian/Pacific Islander patients had 29%, 27%, and 23% lower odds of receiving PC than White patients. Patients in the two lowest income quartiles had 12% and 22% lower odds of receiving PC compared with the highest quartile. Conclusions: PC utilization in patients with ESLD is associated with decreased invasive procedures, shorter lengths of stay, and lower hospitalization charges. Minorities, as well as patients in the lower income quartiles, were less likely to receive PC.

Fecal calprotectin in patients with liver cirrhosis.

Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis. A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population. The mean FCAL (µg/g) level in healthy control (n = 5), stable cirrhotics (n = 10), ESLD (n = 10) and ACLF (n = 10) patients was 109.2 (95% CI: - 53.39 to 271.79), 143.3 (95% CI: 50.5-236.45), 176.9 (95% CI: 122.93-230.87) and 543.5 (95% CI: 207.09-879.91) (p = 0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p = 0.005) and FCAL ≥ 200µg/g (OR = 10.8, p = 0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) μg/g,p = 0.005. FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of ≥ 200µg/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality.