Liver Transplant Patients Research Articles

Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.

Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy. In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators. Patients in the placebo group, if prescribed, received 32 mg of methylprednisolone, while patients in the larsucosterol groups received matching placebo capsules. The primary end point was 90-day mortality or liver transplant (LT) rate. The key secondary end point was 90-day mortality. We prespecified the reporting of U.S. results separately. Among 307 enrolled patients, 301 received at least one treatment dose. The difference in 90-day mortality or LT between the 30-mg or 90-mg larsucosterol and placebo groups did not reach statistical significance. Ninety-day mortality in the placebo and the 30-mg and 90-mg groups was 25 out of 103, 15 out of 102, and 17 out of 102, respectively. Among U.S. patients (76% of all enrolled patients), there were 21 deaths and 4 LTs among 77 patients in the placebo group, 8 deaths and 5 LTs among 73 patients in the 30-mg larsucosterol group, and 10 deaths and 8 LTs among 77 patients in the 90-mg larsucosterol group. In patients who were treated within less than 10 days of hospitalization (75%), mortality in the placebo group was 20 out of 79 (U.S. patients 17/57), mortality in the 30-mg larsucosterol group was 7 out of 74 (U.S. patients 4/57), and mortality in the 90-mg larsucosterol group was 13 out of 77 (U.S. patients 9/66). Most adverse events arising during treatment were attributable to hepatic disease, and there was no imbalance in adverse events that could not be ascribed to liver disease. The trial did not meet the primary end point of showing a beneficial effect of larsucosterol on 90-day mortality or LT in patients with severe AH. Equipoise has been established for a further trial of larsucosterol on AH survival. (The trial was funded by the DURECT Corporation; its ClinicalTrials.gov number is NCT04563026.).

Effect of gut microbiota changes on cytokines IL-10 and IL-17 levels in liver transplantation patients

BackgroundLiver transplantation (LT) is a critical intervention for individuals with end-stage liver disease; yet, post-transplant problems, especially infections, graft rejection, and chronic liver disease, are often linked to systemic inflammation. Cytokines, small signaling molecules, significantly influence immune responses during and post-liver transplantation. Nonetheless, the intricate relationships among cytokines, immune responses, and the gut microbiota, especially gut dysbiosis, are still inadequately comprehended. Thus, this study aims to identify the gut microbiota (GM) and determine their relationship to cytokines (IL-17 and IL-10) in LT patients, due to their importance in enhancing the recovery rate.ResultThe research included 31 liver transplant (LT) patients from the Gastroenterology Surgical Center at Mansoura University, resulting in the collection of 174 stool and blood samples from all participants. Fourteen bacterial species have been identified in samples collected at three intervals: one week before, one week post, and two weeks post LT. A change in gut microbiota composition was noted, characterized by a rise in potentially pathogenic bacteria such as Enterococci and Enterobacteriaceae (including Escherichia coli and Klebsiella) and a reduction in beneficial bacteria such as Bacteroidetes and Firmicutes. The examination of patient demographic and clinical data revealed no significant correlations between sex, age, or diagnostic categories and gut microbiota composition. The findings of the Multivariate Analysis of Variance (MANOVA) indicated a substantial effect of gut microbiota composition on cytokine levels (IL-10 and IL-17), with all tests producing p-values of 0.001. The assessment of cytokine levels indicated fluctuating variations at several time points following surgery. IL-10 levels in the GM groups exhibited a statistically significant elevation during the second week post-surgery (p = 0.036), suggesting a potential recovery-related anti-inflammatory response. In contrast, IL-17 levels rose in the NI group over time, indicating a transition to a pro-inflammatory condition.ConclusionThis study emphasizes the pivotal role of the gut microbiota in regulating immune responses following transplantation.

P-706. Adenovirus Type 21 Outbreak among Haematology and liver transplant patients at a large tertiary care hospital in Singapore

Abstract Background Human adenoviruses (HAdVs) commonly cause acute respiratory illness, with documented outbreaks in military settings. HAdV infections frequently precipitate severe pneumonia amongst immunocompromised patients, with associated mortality risk. We report a HAdV type 21 infection cluster involving immunocompromised patients at a tertiary care hospital. Methods Hospital-onset (HO) adenoviral infection was defined as positive HAdV polymerase chain reaction (PCR) test with corresponding respiratory symptom onset six days after admission. Positive samples were typed in the National Public Health Laboratory by sequencing hexon gene variable regions. Epidemiological investigations were carried out for potential spatiotemporal linkage between these patients for targeted infection prevention interventions. Results Between 1st January to 31st March 2024, 21 HAdV-positive cases were identified, with five categorised as HO HAdV. Four patients (80%) had haematological malignancies and one had received a liver transplant 23 days prior to testing positive for HAdV. The mean age of patients was 58.6 years (SD: ± 9.7), with males comprising 60% of the cohort. The median hospital length of stay (LOS) before HAdV positivity was 21 days (range: 6 – 45). Clinical manifestations included fever, shortness of breath, cough, and acute respiratory failure. All patients required Intensive Care Unit (ICU) admission, with an average ICU LOS of 10 days (SD: ± 9.2). Respiratory samples of three patients were typed as HAdV 21, and three had adenovirus DNAemia. In the identified cluster, the four patients with haematological malignancies shared the same ward, with two overlapping in time but housed in different rooms. The liver transplant patient had overlapping stay in the critical care unit with a patient from the haematology cluster and shared the same mobile chest x-ray machine with two others from the same cluster. All four patients with haematological malignancies experienced same-admission mortality. Conclusion Timely symptom recognition and respiratory multiplex panel testing enabled detection of HAdV infection cluster in immunocompromised patients. Early cluster detection and reinforcement of infection prevention measures at risk locations can mitigate transmission of HAdV infections. Disclosures Moi Lin Ling, FRCPA, Solventum: Honoraria|Solventum: Educational grant for APSIC projects

636. Pneumocystis Pneumonia Outcomes in Solid Organ Transplant Recipients and Patients Living with HIV: A Population-Based Study Over 20 Years (2002-2022) in Ontario, Canada

Abstract Background While it is well established that HIV-positive and non-HIV immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP), comparing PCP outcomes between patients with different underlying immunocompromising conditions is critically important to optimize chemoprophylaxis strategies. Methods In this population-based cohort, we determined contributing factors to 90-day all-cause mortality following PCP diagnosis among patients living with HIV (PLWH) and solid organ transplant recipients (SOTRs) hospitalized in Ontario, Canada between Apr/1/2002 and Dec/31/2022. We linked data from provincial health administrative databases using unique encoded identifiers and included all adult patients hospitalized with PCP based on diagnostic codes from hospital discharge abstracts. We used logistic regression models to estimate unadjusted and adjusted odds ratios (uOR and aOR) and 95% confidence intervals (95%CI) for the associations between underlying immunocompromising conditions and PCP outcomes. Results A total of 879 patients were hospitalized with PCP, including 121 SOTRs (13.7%) and 758 PLWH (86.2%). 90-day mortality rates were 19.8% in SOTRs and 13.2% in PLWH. In the unadjusted model, 90-day mortality was not significantly associated with organ transplantation (OR=1.58; 95%CI, 0.96-2.62) or HIV infection (OR=0.62; 95%CI, 0.38-1.03). Comparing HIV patients to liver SOTRs, liver SOTRs experienced higher mortality (uOR=8.54, 95%CI=3.11-23.46). In the adjusted model, liver transplantation was associated with an increased risk of 90-day mortality (aOR=4.36; 95%CI, 1.40-13.59). Among SOTRs, in the unadjusted analysis, liver transplant recipients had an increased risk of 90-day mortality (uOR=9.18; 95%CI, 3.00-28.09). Conclusion Among SOTRs, liver transplant recipients are at particularly higher risk of mortality following PCP diagnosis. Our findings may prompt a re-evaluation of current PCP prophylactic strategies in liver transplant patients. Disclosures All Authors: No reported disclosures

P-2255. Peri-Transplant Antibiotic Use and Multidrug Resistant Infections in Liver Transplantation

Abstract Background Understanding antibiotic use patterns and risk of infection with multi-drug resistant organisms (MDROs) in the peri-transplant period is crucial to successful post-liver transplant care. Methods Clinical data from patients who underwent liver transplant after the initiation of ICD-10 coding were obtained using Stanford University’s central database. Data were processed and analyzed in R studio and Excel. Results During the study period, 645 patients underwent liver transplantation. The median age at transplantation was 60.8 years (IQR 18.9, 82.4) and 222/645 (34%) were female. In the 30-day pre-transplant period, 21/645 (3%) patients developed bacteremia or fungemia, and in the 30-day post-transplant period, 30/645 (5%) patients developed bacteremia or fungemia. Enterococcus faecium was the most common cause of bacteremia (25/60 positive blood cultures), followed by enteric gram-negative rods (16/60 positive blood cultures). All E. faecium causing bacteremia was vancomycin resistant (25/25, 100%), and 9/16 (56%) gram negative rod isolates from blood were MDROs. The overall antibiotic days per thousand inpatient days in the 30-day pre- and post-transplant period was 374. The most used group of antimicrobials was anti-Pseudomonal β-lactams, with 255.4 days of use per thousand inpatient days (Figure 1). Vancomycin had 83.8 days of use per thousand inpatient days but was more frequently used in patients who had an MDRO isolated from at least one body site than in patients who did not have an MDRO isolated (104.7 days vs 76.8 days per thousand inpatient days). Patients with at least one MDRO isolated 30 days pre- or post-transplant had significantly higher 90-day and 1-year mortality compared with patients who had positive cultures but did not have an MDRO isolated (12.1% vs 1.8%, p=0.01; 17.6% vs 7.3%, p=0.02), as well as a longer length of post-transplant hospitalization that did not meet statistical significance (14.3 days vs 10.8 days, Table 1). Conclusion Liver transplant patients are at high risk for colonization and infection with MDROs in the peri-transplant period and have high rates of antimicrobial use. For this patient cohort, presence of an MDRO is associated with higher rates of mortality and longer lengths of stay in the post-transplant period. Disclosures All Authors: No reported disclosures

P-2278. CMV Viremia and Disease in Pediatric Liver Transplant Patients: a Multi-national Systematic Review and Meta-analysis

Abstract Background Cytomegalovirus (CMV) viremia (Defined as a single detectable CMV RNA PCR) and disease (defined as CMV viremia with compatible systemic and/or localized signs and symptoms) remain a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient. This systemic review aims at pooling data from the leading pediatric transplant institutions globally to identify the overall incidence of and risk factors associated with CMV viremia and/or disease in pediatric liver transplant recipients. PRISMA flow diagram Methods A systemic review of Pubmed and OVID databases was conducted since the inception to 01 April 2024. 24 articles were included from the USA, UK, South Africa, India, Japan, Finland, Canada, Turkey, Mexico, Thailand, Greece, Israel and Australia. A total of 1964 liver transplants were included. Median age was 50 months with 47.8% males. Data related to demographics, incidence, donor and recipient CMV serological classification (Donor (D) and Recipient (R)) and risk factors for CMV viremia/disease were extracted from the articles and subsequently analysed. This review was registered in Prospero: CRD42023477476 Results The Incidence of CMV viremia and disease in pediatric liver transplant patients in this review were 34% and 8.4% respectively, with statistically significant higher risk in the CMV D+/R+ category compared to other D/R serologic groups (P value < 0.05). , Additional risk factors identified for CMV viremia/disease included younger age, biliary atresia, high steroid doses, and rejection attacks. Conclusion This meta-analysis highlights that CMV viremia and disease post-liver transplantation are significant health concerns in pediatric populations. Identifying high risk populations for targeted CMV monitoring and potentially preemptive therapy to mitigate CMV-associated morbidity and mortality is a critical cornerstone of pediatric transplant medicine. Further studies are warranted to explore additional risk factors and to refine prevention and treatment strategies for CMV in pediatric transplant recipients. Disclosures All Authors: No reported disclosures

Association of LR treatment response category with outcome of patients with hepatocellular carcinoma on explant pathology.

Liver transplant (LT) is an effective treatment for hepatocellular carcinoma (HCC) in appropriately selected patients. Locoregional therapy (LRT) is often performed to extend a patient's eligibility for LT. Imaging has a modest sensitivity of approximately 40-77% for detecting pathologically viable HCC in post-LRT patients. The impact on overall survival (OS) and disease-free survival (DFS) is unclear. We hypothesize that Liver Imaging Reporting & Data Systems Treatment Response (LI-RADS TR) category is equivalently correlated with long-term survival and overall disease-free progression when compared to explant pathology findings. We additionally hypothesize that neoadjuvant LRT can improve OS and DFS in LT patients initially within MC. Patients found to have HCC on explant between January 2005 and December 2021 were included. A total of 167 patients were divided into treatment (any pre-LT LRT except for Y-90 therapy) and control (no pre-LT LRT) groups. Of the patients who received pre-LT LRT, imaging studies were reviewed by two abdominal radiologists using 2018 LI-RADS criteria. Statistical analysis was performed using Kaplan-Meier survival curves and Cox proportional hazard models to assess OS and DFS. No statistically significant difference in OS or DFS (p = 0.23 and p = 0.22 respectively) was initially found. Given significant difference in age between the groups (p < 0.0001), Cox proportional hazard models were used to adjust for age with statistical significance reached for better OS and DFS in the treatment group (p = 0.05 and p = 0.05 respectively). Contrary to our hypothesis, there was no difference between treatment response groups regarding overall survival or disease-free survival, presumably because of low number of HCC recurrences in our patient population (4%). Despite not reaching statistical significance, LI-RADS TR categorization demonstrates a good interreader agreement (Kappa 0.6), helping radiologists feel comfortable that modest sensitivity of the LI-RADS TR treatment response category for detecting pathologically active malignancy does not confer a negative clinical outcome.

Understanding the Impact of Obesity on Liver Transplant Outcomes: A Comprehensive Analysis.

The purpose of this investigation is to assess how effective it is to exclude individuals from the liver transplant (LT) using the body mass index (BMI) as a criterion. A retrospective longitudinal analysis of patients with liver transplant outcomes from January 2001 to May 2020 was conducted using the United Network for Organ Sharing (UNOS) database. A total of 118,486 LT cases included in the study. Based on their BMI, patients were split into three groups: a BMI<35kg/m2, a 35≤BMI < 40kg/m2, and a BMI≥40kg/m2. The data analysis revealed a significant improvement in 10-year graft survival in the 2011-2020 group compared to the 2001-2010 group (mean 70% vs. 53% and P<0.001). Interestingly, a BMI above 35kg/m2 did not have a significant effect on the graft survival, and in both time frames, there was no clinically significant difference between the recipients of the different BMI spectrum. The patient's survival was also characterized by the same pattern. Primary graft failure was the most significant cause of allograft transplant failure in all the BMI spectrum, except recipients with a BMI<35kg/m2, in 2011-2020 group. The outcomes of LT in patients requiring a LT are not significantly affected using the BMI, considering the advancements in surgical techniques and postoperation improvements, and excluding obese patients based on the BMI alone would be inappropriate.

Evaluation of hypotension prediction index software in patients undergoing orthotopic liver transplantation: retrospective observational study.

Extreme hemodynamic changes, especially intraoperative hypotension (IOH), are common and often prolonged during Liver Transplant (LT) surgery and during initial hours of recovery. Hypotension Prediction Index (HPI) software is one of the tools which can help in proactive hemodynamic management. The accuracy of the advanced hemodynamic parameters such as Cardiac Output (CO) and Systemic Vascular Resistance (SVR) obtained from HPI software and prediction performance of the HPI in LT surgery remains unknown. This was a retrospective observational study conducted in a tertiary academic center with a large liver transplant program. We enrolled 23 adult LT patients who received both Pulmonary Artery Catheter (PAC) and HPI software monitoring. Primarily, we evaluated agreement between PAC and HPI software measured CO and SVR. A priori, we defined a relative difference of less than 20% between measurements as an adequate agreement for a pair of measurements and estimated the Lin's Concordance Correlation Coefficient and Bland-Altman Limits of Agreement (LOA). Clinically acceptable LOA was defined as ±1 L.min-1 for CO and ±200 dynes s.cm-5 for SVR. Secondary outcome was the ability of the HPI to predict future hypotension, defined as Mean Arterial Pressure (MAP) less than 65 mmHg lasting at least one minute. We estimated sensitivity, positive predictive value, and time from alert to hypotensive events for HPI software. Overall, 125 pairs of CO and 122 pairs of SVR records were obtained from 23 patients. Based on our predefined criteria, only 42% (95% CI 30%, 55%) of CO records and 53% (95% CI 28%, 72%) of SVR records from HPI software were considered to agree with those from PAC. Across all patients, there were a total of 1860 HPI alerts (HPI ≥85) and 642 hypotensive events (MAP< 65 mmHg). Out of the 642 hypotensive events, 618 events were predicted by HPI alert with sensitivity of 0.96 (95% CI: 0.95). Many times, the HPI value remained above alert level and was followed by multiple hypotensive events. Thus, to evaluate PPV and time to hypotension metric, we considered only the first HPI alert followed by a hypotensive event ("true alerts"). The "true alert" was the first alert when there were several alerts before a hypotension. There were 614 "true alerts" and the PPV for HPI was 0.33 (95% CI 0.31, 0.35). The median time from HPI alert to hypotension was 3.3 [Q1, Q3: 1, 9.3] mins. There was poor agreement between the pulmonary artery catheter and HPI software calculated advanced hemodynamic parameters (CO and SVR), in the patients undergoing LT surgery. HPI software had high sensitivity but poor specificity for hypotension prediction, resulting in a high burden of false alarms.

Perioperative Variation of Plasma Copeptin and Its Association With Vasopressor Need During Liver Transplantation.

Vasopressor usage during liver transplant is related to decreased hepatic flow, graft failure, and mortality. We measured plasma Copeptin levels in liver transplant patients based on vasopressor requirements. We hypothesize that preoperative plasma copeptin measurement helps predict the vasopressor infusion requirement during liver transplantation in preoperative evaluation. The plasma Copeptin of 40 patients was measured 5 times: before the operation, 15 minutes before and after reperfusion, and postoperative 12th and 24th hours. Patients were categorized into 2 groups based on vasopressor infusion for comparison. There was a statistically significant rise in median serum Copeptin concentration between the preoperative phase and before reperfusion (11.2 [7.3-20.9] vs 178.5 [121.5-243.0], P < .001), as well as a statistically substantial decline between after reperfusion and postoperative 12th hours (190.6 [127-276.3] vs 74.7 [42.0-124.9], P < .001). The vasopressor-taking group had significantly higher plasma copeptin at postoperative 12th hours (96.6 [71.4-191.7] vs 55.0 [31.8-82.5], P = .030) and 24th (133.7 [72.2-175.5] vs 51.1 [24.8-85.8], P = .037). A tendency above 11.85 pmol/L of plasma Copeptine level was observed between increasing preoperative plasma Copeptin and the odds of vasopressor use. High preoperative plasma Copeptin levels may be an indicator of vasopressor need during liver transplantation. Further studies with more samples, including a higher range of preoperative plasma Copeptin levels, are required to provide more generalizable findings and to determine thresholds applicable to LT candidates.

Recurrent Portal Hypertension after Liver Transplant: Impact on Survival and the Role of TIPS Creation in Management.

Recurrent portal hypertension (PH) after liver transplant (LT) and its management are not well-studied. This study aims to evaluate the impact of transjugular intrahepatic portosystemic shunt (TIPS) on outcomes of recurrent PH. From a cohort of 1846 LT recipients, 36 patients who underwent TIPS creation after LT were identified and considered as cases. To streamline comparison with the remaining LT patients without TIPS, a representative subset comprising more than 20% of the entire population (381/1810) was randomly selected. Diuretic refractory ascites, and endoscopic findings were reviewed to detect recurrent PH in patients without TIPS. Repeat transplantation, and graft and overall survival were compared between recurrent PH patients with and without TIPS. Survival analysis with multivariable Cox regression analysis was used for risk factors of survival. Out of 1846 patients, 36 (2%) underwent TIPS after LT. Among the control group, 24 (of 381, 6.3%) patients had recurrent PH. TIPS resulted in ascites resolution in 25 (of 36, 74%). Repeat transplant was more frequent in recurrent PH without TIPS, than recurrent PH with TIPS (33% vs. 11%, p=0.035). Median overall survival after TIPS was 2.4 years (95% CI: 0.6-3.2). Transplant-free survival after initial LT was not different between patients with or without TIPS (8.6 years vs. 7.6 years, p=0.360). Multivariable Cox regression showed that repeat transplant was associated with reduced mortality in recurrent PH (HR=0.15, p=0.016). Recurrent PH after LT is rare, but adversely impacts patient outcomes. However, TIPS in recurrent PH improves ascites without worsening survival.

Friend or Foe? Safety and Efficacy of Hepatitis B Viremic Solid Organ Allograft into Seronegative Recipients.

Long-term outcomes of HBV nucleic acid test (NAT)-positive (+) allograft use in seronegative liver transplant (LT) and kidney transplant (KT) recipients remains unknown despite being incorporated into practice by select centers. This study compares long-term outcomes between HBV NAT+ and NAT-negative (-) allografts in seronegative recipients. All recipients of an HBV core antibody-positive (HBcAb+) LT or KT were prospectively evaluated at a single transplant center from 6/2015-3/2023 and compared by NAT status. Study endpoints were post-transplant viremia, patient, and graft survival. 144 HBcAb+ LT and 220 HBcAb+ KT were performed including 57 (39.6%) NAT+ LT's and 123 (55.9%) NAT+ KT's with a median follow-up of 36 months. 14.8% of NAT+ and 3.5% of NAT- LTs experienced post-transplant viremia (p=0.004). At the time of last follow-up, 100% of NAT+ and 98.9% of NAT- LT recipients had undetectable HBV DNA (p=0.31). 4.1% of NAT+ and 6.2% of NAT- KTs experienced post-transplant viremia (p=0.12). At the time of last follow-up, 100% of NAT+ and 96.9% of NAT- KT recipients had undetectable HBV DNA (p=0.85). LT and KT patient and graft survival were not different between groups (p>0.05). With close surveillance, HBV seronegative recipients transplanted with NAT+ allografts can develop viremia which can be cleared with antiviral therapy. This is the first and largest single-center study reporting longer-term experience with HBV NAT+ allografts in seronegative recipients demonstrating the safe expansion of the donor pool.

A Supervised Explainable Machine Learning Model for Perioperative Neurocognitive Disorder in Liver-Transplantation Patients and External Validation on the Medical Information Mart for Intensive Care IV Database: Retrospective Study.

Patients undergoing liver transplantation (LT) are at risk of perioperative neurocognitive dysfunction (PND), which significantly affects the patients' prognosis. This study used machine learning (ML) algorithms with an aim to extract critical predictors and develop an ML model to predict PND among LT recipients. In this retrospective study, data from 958 patients who underwent LT between January 2015 and January 2020 were extracted from the Third Affiliated Hospital of Sun Yat-sen University. Six ML algorithms were used to predict post-LT PND, and model performance was evaluated using area under the receiver operating curve (AUC), accuracy, sensitivity, specificity, and F1-scores. The best-performing model was additionally validated using a temporal external dataset including 309 LT cases from February 2020 to August 2022, and an independent external dataset extracted from the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database including 325 patients. In the development cohort, 201 out of 751 (33.5%) patients were diagnosed with PND. The logistic regression model achieved the highest AUC (0.799) in the internal validation set, with comparable AUC in the temporal external (0.826) and MIMIC-Ⅳ validation sets (0.72). The top 3 features contributing to post-LT PND diagnosis were the preoperative overt hepatic encephalopathy, platelet level, and postoperative sequential organ failure assessment score, as revealed by the Shapley additive explanations method. A real-time logistic regression model-based online predictor of post-LT PND was developed, providing a highly interoperable tool for use across medical institutions to support early risk stratification and decision making for the LT recipients.

Deep sequencing-derived Metagenome Assembled Genomes from the gut microbiome of liver transplant patients

Recurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) after liver transplantation (LT) is a continuing concern. The role of gut microbiome dysbiosis in MASLD initiation and progression has been well established. However, there is a lack of comprehensive gut microbiome shotgun sequence data for patients experiencing MASLD recurrence after LT. In this data descriptor, we describe a dataset of deep metagenomic sequences of a well-defined LT recipient population. Community-based analysis revealed a high abundance of Akkermansia muciniphila, consistently observed in most patient samples with a low (0–2) MASLD Activity Score (NAS). We constructed 357 metagenome-assembled genomes (MAGs), including 220 high-quality MAGs (>90% completion). The abundance of different species of Bacteroides MAGs dominated in patient samples with NAS > 5 (“definite MASH”). In contrast, the MAGs of A. muciniphila, Akkermansia sp., and Blutia sp. dominated in samples from patients without MASH (NAS = 0–2). In addition, the phylogenetic analysis of A. muciniphila and Akkermansia sp. MAGs identified two new phylogroups of Akkermansia that are distinct from the previously reported three phylogroups.

Disadvantage of Viable Portal Vein Tumor Thrombosis in Liver Transplantation for Advanced Hepatocellular Carcinoma.

Liver transplantation (LT) is a promising treatment option for patients with hepatocellular carcinoma (HCC) comorbid with cirrhosis. However, HCC with portal vein tumor thrombosis (PVTT) remains an absolute contraindication for LT. This study aimed to analyze the outcomes of LT in patients with HCC plus portal vein thrombosis and further evaluate the impact of PVTT on the long-term outcomes of patients. Among the 501 patients who underwent LT for HCC between January 2000 and March 2023, 29 (5.8%) patients with HCC who had portal vein thrombosis were further analyzed. Of these 29 patients with portal vein thrombosis, 12 (41.4%) were preoperatively diagnosed with PVTT and underwent LT after receiving downstaging therapy. The remaining 17 (58.6%) patients were PVTT-free prior to LT. Overall, the recurrence-free survival rates at 1, 3, and 5 years were 96.3%, 74.2%, and 74.2%, respectively, while the 1-, 3-, and 5-year overall survival rates were 82.4%, 74.2%, and 70.1%, respectively. However, patients with viable PVTT had significantly worse outcomes than those without viable PVTT (p = 0.030). The 5-year recurrence-free and overall survival rates for patients with viable PVTT were 57.5% and 57.0%, respectively. LT may still be a promising option for patients with HCC and PVTT after appropriate downstaging. However, caution should be adopted, as remnant viable PVTT might lead to unsatisfactory outcomes after transplantation.

Liver Transplantation in Well-Selected Class III Obese Recipients Yields Good Outcomes.

Previous guidelines considered body mass index (BMI) over 40kg/m2 a relative contra-indication to liver transplantation (LT). The aims were to examine the selection process and study outcomes of patients with Class I-III obesity. Retrospective analysis of outcomes of obese patients assessed for LT at our center between 2010 and 2023, divided into three groups: Class I (BMI30-34.9kg/m2), Class II (BMI35-39.9kg/m2), and Class III (BMI>40kg/m2). Survival of non-obese adult patients was used for comparison. Three hundred fifteen patients with BMI ≥30kg/m2 were assessed for LT. Seventeen (5.4%) were not wait-listed due to comorbidities. One hundred sixty-eight patients were transplanted: 100 Class I, 43 Class II, and 25 Class III. There were no differences in postoperative complications (Clavien-Dindo Grade 3 or more; 41%, 42%, 48% for Class I-III obesity respectively) or patient and graft survival (5-y rates 84.4% and 82.7%, respectively, for the whole cohort) according to the different classes of obesity. Furthermore, patient and graft survival was not different between non-obese and obese patients (p = 0.932). With a rigorous selection process, short-term outcomes after LT for patients with Class III obesity were comparable to patients with Class I-II obesity. Long-term survival was identical for obese and non-obese patients.

Morbid Obesity and Liver Transplant.

The progressive increase in the prevalence of morbid obesity (MO) in the general population is a pressing issue. This rise in MO has also been observed in patients with liver disease who are candidates for liver transplantation (LT). A retrospective study of a single-center series was conducted to analyze the impact of MO on morbidity, mortality, and patient survival after LT. Fifteen patients with a body mass index (BMI) of ≥ 40 kg/m2 (mean 40.4 ± 2.99 SD) were transplanted from 2004 to 2023. Thirteen were 13 men (87%) and 2 women (13%), with a mean age of 55 years (±9). The most common indication for LT was liver cirrhosis (93%: 6 alcohol related, 4 hepatitis C virus [HCV] related, and 3 from other causes), and only one case was due to hepatocellular carcinoma in a non-cirrhotic liver (7%). The median stay in the Intensive Care Unit was 5 days (range 2-52), with a median total hospital stay of 15 days (range 10-103). Five patients had a major complication each (≥ IIIa on the Clavien-Dindo scale): liver re-transplantation due to primary graft failure, reoperation due to hemoperitoneum, late superior mesenteric vein (SMV) thrombosis, acute renal failure that required hemodialysis, and surgical wound infection that required drainage. The only patient who required urgent re-transplantation (7%) had an adequate subsequent recovery without other complications. None of the patients underwent obesity surgery pre-, post-, or concurrently with the LT. Patient and graft survival after 5 years was 97%. In our experience, the outcomes of LT in patients with MO were satisfactory in terms of postoperative morbimortality, as well as in patient survival. Therefore, we do not support the notion of considering MO as a contraindication for LT.

Does Weekend Discharge Affect Readmission and Survival in Liver Transplant Patients? Insights From a Cohort Study.

Weekend hospital discharges are often associated with reduced staffing, potentially impacting the quality of patient care. We studied the effects of weekend discharge after liver transplantation (LT) on early readmission rates, overall survival (OS), and graft survival (GS). We analyzed data from the Ohio State University Wexner Medical Center database (January 2016 to December 2023). The study included initial LT recipients (LTRs) including donation after brain death (DBD) and donation after cardiac death (DCD). Primary outcomes encompassed early readmission rates, and secondary outcomes included OS and GS. The cohort comprised 915 LTRs (645 DBD, 270 DCD), with 156 (17.0%) weekend and 759 (83.0%) weekday discharges. Regarding discharge disposition, 681 (74.4%) patients were discharged home, 210 (22.9%) were discharged to healthcare facilities. No significant differences were identified in the length of hospital stay (8 days vs. 9 days, weekend vs. weekday, respectively, p=0.22) or 30-day readmission (29.5%vs. 32.5%, weekend vs. weekday, respectively, p=0.75). There were no significant differences in OS (90.9%vs. 92.7% at 1-year, 84.4%vs. 88.0% at 3-year, weekend vs. weekday, p=0.27) and GS (90.9%vs. 91.5% at 1-year, 84.0%vs. 86.6% at 3-year, weekend vs. weekday, p=0.50). Multivariate logistic analysis showed no significant impact of weekend discharge (OR: 0.84 [0.57-1.22], p=0.35) or discharge disposition (OR: 1.00 [0.75-1.33], p=1.00) on 30-day readmission. Multivariate Cox regression analysis found no significant impact of weekend discharge or discharge disposition on OS and GS (all p>0.05). Weekend discharge does not impact early readmission, OS, or GS in LTRs. These findings are a testament to our multidisciplinary team efforts and suggest that with appropriate discharge planning and follow-up care, the timing of discharge may be less critical than previously assumed.

The impact of visitation volunteers on the mood, valence, and arousal of liver and kidney transplant patients

The impact of visitation volunteers on the mood, valence, and arousal of liver and kidney transplant patients

Perioperative Outcomes and Mortality in Liver Transplant Patients 65 and Older

Perioperative Outcomes and Mortality in Liver Transplant Patients 65 and Older