Outcomes In Liver Transplant Recipients Research Articles

The Influence of Invasive Candida Infections on Prognosis and Analysis of Their Risk Factors After Liver Transplantation

PurposeThis study aimed to investigate the incidence, timing, risk factors, and impacts of invasive Candida infections (ICIs) within 3 months after liver transplantation (LT) on LT recipients’ prognosis. MethodsPatients undergoing LT from January 2015 to December 2022 in a tertiary university hospital were investigated the incidence, onset, and risk factors of ICIs and the effects of ICIs on the outcome of LT recipients using statistical methods. FindingsThe mean age of involved 389 LT recipients was 47.3 ± 10.5 years, with 322 (82.8%) being men. The incidence of ICIs was 3.3% (13/389), and the median time between LT and onset of ICIs was 5.0 days. The univariate analysis of predictors of ICIs identified that massive blood loss, prolonged duration of central line and urethral catheter, and prophylactic antifungal therapy were related to post-LT ICI risk. Multivariate logistic regression analysis adjusted for men and age identified that intraoperative blood loss ≥5000 mL (odds ratio [OR] = 7.005, 95% CI: 2.084–23.542, P = 0.002) and central line duration >14 days (OR = 5.270, 95% CI: 1.556–17.854, P = 0.008) were independently associated with the development of post-LT ICIs. Post-LT prophylactic antifungal therapy >3 days reduced ICIs (OR = 0.103, 95% CI: 0.021–0.501, P = 0.005). Regarding clinical outcomes, patients with ICIs were more likely to stay in the intensive care unit for 7 days or longer compared with those without ICIs (OR = 6.910, 95% CI: 1.737−27.493, P = 0.006). ICIs had no impact on hospitalization stay and 1-month all-cause mortality after LT. ImplicationsICIs are frequent and occur early after LT. Predictors of post-LT ICIs were massive intraoperative blood loss and prolonged duration of the central line. However, post-LT prophylactic antifungal therapy reduced ICIs. Patients with ICIs stayed longer in the intensive care unit than those without ICIs.

223.11: The impact of loco-regional therapy on long term outcomes of liver transplant recipients for hepatocellular carcinoma.

223.11: The impact of loco-regional therapy on long term outcomes of liver transplant recipients for hepatocellular carcinoma.

Role of Endotherapy in Outcome of Liver Transplant Recipients Complicated by Post-Transplant Biliary Strictures

Role of Endotherapy in Outcome of Liver Transplant Recipients Complicated by Post-Transplant Biliary Strictures

Vibration-Controlled Transient Elastography–Based Parameters Predict Clinical Outcomes in Liver Transplant Recipients

Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P= .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P= .017). The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.

Association of Preoperative Red Cell Distribution Width with Postoperative Outcomes in Liver Transplantation Recipients

Background: The 1-year mortality rate after liver transplantation is approximately 8%-20%. It is important to explore risk factors associated with postoperative outcomes in liver transplantation recipients (LTRs). Red cell distribution width (RDW) is an indicator that assesses the variability in the volume of red blood cells in circulation. RDW is not only related to inflammatory levels and nutritional status but also associated with postoperative outcomes in surgical patients. However, the relationship between preoperative RDW and postoperative outcomes in LTRs remains unclear. Therefore, we designed a retrospective observational study to investigate the impact of preoperative RDW levels on postoperative outcomes in LTRs. Methods: We retrospectively collected clinical data of patients who underwent allogeneic liver transplantation at West China Hospital, Sichuan University, from January 2016 to December 2020. The primary outcome was 1-year mortality. Secondary outcomes included 30-day mortality, long-term survival, early postoperative graft dysfunction, acute kidney injury, renal replacement therapy, pulmonary complications, duration of postoperative mechanical ventilation, length of ICU stay, and length of hospital stay. Patients were divided into two groups: RDW ≤ 14.5% and RDW &gt; 14.5%. We selected 14 covariates and used propensity score matching (PSM) to adjust for baseline characteristics. Postoperative outcomes and long-term survival were analyzed after PSM. Receiver operating characteristics (ROC) curves and subgroup analyses were also performed. Results: A total of 661 patients who underwent liver transplantation surgery were screened for this study. Finally, 438 patients were included in the statistical analysis. After PSM, there were no statistically significant differences in postoperative mortality and complications between the RDW ≤ 14.5% group and the RDW &gt; 14.5% group (P &gt; 0.05). The comparison of long-term survival between the two groups also showed no statistical difference (hazard ratio = 0.67, 95% confidence interval: 0.28-1.61, P = 0.358). Subgroup analyses showed consistent results. The ROC curve indicated that the predictive ability of preoperative RDW levels for 1-year mortality is moderate (area under the ROC curve 0.661). Conclusion: Preoperative RDW levels do not affect postoperative mortality and the incidence of complications in LTRs. However, these results still need further research for verification.

Outcomes of liver transplant recipients with pretransplant malignancies: Insights from a single institution’s experience.

11173 Background: Increasing liver transplantation (LT) utilization has resulted in more and more patients with a history of a non-hepatobiliary malignancy. Rather than deny such patients a lifesaving therapy the benefits must be weighed against risk of tumor recurrence and de novo malignancies (DNM) post-LT, especially with the immunosuppression required. While data has been presented on outcomes of pre transplant malignancies (PTM) in kidney and heart transplants, LT data is lacking. Our aim is to characterize rates of recurrence, DNM, and overall survival (OS) post-LT at a single, high volume American center. Methods: This retrospective study at Houston Methodist Hospital included patients who underwent LT with known history of PTM. Data was extracted from electronic health records, and descriptive statistics performed. Institutional IRB approval is obtained. Results: Between 01/1999- 12/2022, 1617 LTs were performed at our institute. We identified 261 LT recipients with 297 PTM, including 91 non- and 206 hepatobiliary cancers (See Table). Follow-up period ranged from 1 to 23 years. Post-LT malignancies were observed in 66 patients, 25% of the study population. Tumor recurrences accounted for 44 (17%) cases, and DNM were seen in 22 (8%). The DNMs included skin non-melanoma (n=8 cases), head &amp; neck (3), PTLD (2), prostate (2), renal (1), lung (1), CRC (1), pancreatic (1), gynecologic (2), and poorly differentiated (1). The OS rate at 1-, 5-years (excluding those less than 5 years follow-up and unknown), and at time of last follow-up were 86.6%, 60-65% and 70%, respectively. Patients with post-LT malignancies had lower OS compared to those without (46% vs. 77.7%). Conclusions: To our knowledge, this study is the first to assess post-LT outcomes in patients with PTM. This study of LT recipients with PTM demonstrates post-LT malignancy rates of 25%, including 17% with recurrences and 8% with DNM. The latter is within the previously reported range of 3-14% DNM in the general post-LT population and dominated by skin cancers. Post-LT OS is excellent in these recipients and comparable to all LT patients. However, OS is lower in those with post-LT malignancies, implying a possible role for increased cancer surveillance. Limitations include retrospective design and potential chart bias. Future work in this cohort will focus on immunosuppression effects for this high-risk population. [Table: see text]

Venovenous bypass in liver transplantation: Exploring the benefits, efficacy, and safety.

Venovenous bypass (VVB) is a technique used in liver transplantation (LT) to maintain hemodynamic stability and abdominal organ perfusion and thereby improve patient outcomes. Despite its perceived benefits, VVB utilization has declined globally due to concerns related to heparinization, major bleeding and the need for expertise. Recent advancements, such as percutaneous cannulation techniques and improved extracorporeal technology have improved the safety of VVB in LT. This paper presents a modified VVB circuit with enhanced safety features. Cannulation plays a pivotal role in VVB establishment, with percutaneous methods increasingly favored. Studies demonstrate VVB's efficacy in improving patient outcomes with lower incidence of acute kidney injury and reduced operative time and blood loss, with no added morbidity or mortality. However, its routine use faces challenges, with alternative techniques gaining traction. Our experience highlights VVB's role in various clinical scenarios, including patients with high Model for End-Stage Liver Disease (MELD) scores, challenging surgical anatomy, portal vein thrombosis and pre-existing cardiovascular disease, emphasizing its safety and efficacy. Continued research is needed to optimize VVB techniques and ensure better outcomes for liver transplant recipients.

Klebsiella pneumoniae infections after liver transplantation: Drug resistance and distribution of pathogens, risk factors, and influence on outcomes.

Liver transplantation (LT) is the only curative treatment for end-stage liver disease. However, LT recipients are susceptible to infection, which is the leading cause of early mortality after LT. Klebsiella pneumoniae infections (KPIs) in the bloodstream are common in LT recipients. We hypothesized that KPIs and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may affect the outcomes of LT recipients. To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes. This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University, a tertiary hospital, from January 2015 to January 2023. We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis. KPI incidence was 7.9% (n = 32), with lung/thoracic cavity the most frequent site of infection; the median time from LT to KPI onset was 7.5 d. Of 44 Klebsiella pneumoniae isolates, 43 (97.7%) and 34 (77.3%) were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline, respectively; > 70% were resistant to piperacillin/ tazobactam, ceftazidime, cefepime, aztreonam, meropenem, and levofloxacin. Female sex [odds ratio (OR) = 2.827, 95% confidence interval (CI): 1.256-6.364; P = 0.012], pre-LT diabetes (OR = 2.794, 95%CI: 1.070-7.294; P = 0.036), day 1 post-LT alanine aminotransferase (ALT) levels ≥ 1500 U/L (OR = 3.645, 95%CI: 1.671-7.950; P = 0.001), and post-LT urethral catheter duration over 4 d (OR = 2.266, 95%CI: 1.016-5.054; P = 0.046) were risk factors for KPI. CRKP infections, but not KPIs, were risk factors for 6-month all-cause mortality post-LT. KPIs occur frequently and rapidly after LT. Risk factors include female sex, pre-LT diabetes, increased post-LT ALT levels, and urethral catheter duration. CRKP infections, and not KPIs, affect mortality.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

Impact of preoperative infection on liver transplantation (LT) needs further investigation. From January 1, 2015 to December 31, 2022, 24,122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. Compared to the non-infection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding and biliary complications (all P<0.01), and they had shorter 30-day, 90-day survival and overall survival (OS) (all P<0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the OS in the infection group (both P<0.05). Besides, compared to the non-pulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P<0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P<0.05). Patients in the non-abdominal group also had a higher proportion of postoperative infection than those in the abdominal group (P<0.05). Furthermore, compared to the number=1 group, patients in the number≥2 group were more prone to postoperative effusion and infection (both P<0.01), and they also had shorter 30-day and 90-day survival (both P<0.05). Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study.

Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation. To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients, mainly early allograft dysfunction. This multicenter retrospective study included brain-dead donors and adult liver graft recipients. Donor-recipient matching was obtained through a crossover list. Clinical and laboratory data were recorded for both donors and recipients. Donor hepatectomy, cold ischemia, and warm ischemia times were recorded. Primary outcome was early allograft dysfunction. Secondary outcomes included need for retransplantation, length of intensive care unit and hospital stay, and patient and graft survival at 12 months. From January 2019 to December 2021, a total of 243 patients underwent a liver transplant from a brain-dead donor. Of these, 57 (25%) developed early allograft dysfunction. The median donor hepatectomy time was 29 (23-40) min. Patients with early allograft dysfunction had a median hepatectomy time of 25 (22-38) min, whereas those without it had a median time of 30 (24-40) min (P = 0.126). Donor hepatectomy time was not associated with early allograft dysfunction, graft survival, or patient survival following liver transplantation.

Bulk and single-cell RNA sequencing analysis with 101 machine learning combinations reveal neutrophil extracellular trap involvement in hepatic ischemia-reperfusion injury and early allograft dysfunction

BackgroundHepatic ischaemia–reperfusion injury (HIRI) is a major clinical concern during the perioperative period and is closely associated with early allograft dysfunction (EAD), acute rejection (AR) and long-term graft survival. Neutrophil extracellular traps (NETs) are extracellular structures formed by the release of decondensed chromatin and granular proteins following neutrophil stimulation. There is growing evidence that NETs are involved in the progression of various liver transplantation complications, including ischaemia–reperfusion injury (IRI). This study aimed to comprehensively analyse the expression patterns of NET-related genes (NRGs) in HIRI, identify HIRI subtypes with distinct characteristics, and develop a reliable EAD prediction model. MethodsMicroarray, bulk RNA-seq, and single-cell sequencing datasets were obtained from the GEO database. Initially, differentially expressed NRGs (DE-NRGs) were identified using differential gene expression analyses. We then utilised a non-negative matrix factorisation (NMF) algorithm to classify HIRI samples. Subsequently, we employed machine learning algorithms to screen the hub NRGs related to EAD and developed an EAD prediction model based on these hub NRGs. Concurrently, we assessed the expression patterns of hub NRGs at the single-cell level using the HIRI. Additionally, we validated C5AR1 expression and its effect on HIRI and NETs formation in a rat orthotopic liver transplantation (OLT) model. ResultsIn this study, we identified 11 DE-NRGs in the HIRI context. Based on these 11 DE-NRGs, HIRI samples were classified into two distinct clusters. Cluster1 exhibited a low expression of DE-NRGs, minimal neutrophil infiltration, mild inflammation, and a low incidence of EAD. Conversely, Cluster2 displayed the opposite phenotype, with an activated inflammatory subtype and a higher incidence of EAD. Furthermore, an EAD prediction model was developed using the four hub NRGs associated with EAD. Based on risk scores, HIRI samples were classified into high- and low-risk groups. The OLT model confirmed substantial upregulation of C5AR1 expression in the liver tissue, accompanied by increased formation of NETs. Treatment with a C5AR1 antagonist improved liver function, reduced tissue inflammation, and decreased NETs formation. ConclusionsThis study distinguished two apparent HIRI subtypes, established a predictive model for EAD, and validated the effect of C5AR1 on HIRI. These findings provide novel perspectives for the development of advanced clinical strategies to enhance the outcomes of liver transplant recipients.

Artificial Intelligence in Liver Diseases: Recent Advances.

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases.

Outcomes of Liver Transplant Recipients Hospitalized With COVID-19: A Nationwide Analysis From the United States

IntroductionCurrently available data regarding the impact of liver transplantation on the outcomes of patients hospitalized with COVID-19 is conflicting. This study aims to compare the outcomes and resource utilization between patients with and without a history of liver transplant hospitalized with COVID-19. Methods and materialsThis is a retrospective study using the National Inpatient Sample. All adults hospitalized with COVID-19 in the year 2020 were included. Mortality was the primary outcome, while endotracheal intubation, length of hospital stay, and total hospital charges were the secondary outcomes. ResultsOut of 1,050,720 adults admitted with COVID-19 as the primary diagnosis, 1,455 had a secondary diagnosis of liver transplant. Mortality was not significantly increased in transplant recipients (OR adjusted = 0.69, 95% CI: 0.46–1.03, P = 0.07). Intubation rates and total hospital charges did not differ significantly between liver transplant recipients and patients without a history of liver transplant receipt. LOS was shorter by a coefficient of almost two days in patients with a history of LT (P < 0.001). ConclusionLiver transplant recipients do not appear to be at increased risk of severe COVID-19 and COVID-19 mortality.

Modern glucose-lowering drugs in liver transplant recipients: improvement in weight, glycemic control, and potentially allograft steatosis.

Recurrent allograft steatosis occurs in one-third of transplanted livers. Antidiabetic agents like glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type-2 (SGLT2) inhibitors are effective in the management of obesity and hepatic steatosis in the general population; however, there is limited evidence supporting their use in allograft steatosis. We aimed to evaluate their effects on steatosis, body weight, and glycemic control in liver transplant recipients at our institution. In this single-center retrospective cohort study of liver transplant recipients currently on a GLP1RA or SGLT2 inhibitor (transplanted 2015-2022), we compared clinical and radiological data before medication use and at follow-up. Differences were compared using Wilcoxon signed-rank test. Thirty-seven liver transplant recipients were taking the agents. Diabetes was the most common indication (n = 33) followed by obesity (n = 4). Median follow up was 427 days (301,798). Among those with documented steatosis (n = 21), steatosis improved in 5, worsened in 4, remained unchanged in 1, and change could not be evaluated in 11 due to lack of comparable pre and post imaging. Average weight loss was 3.2 kg (p < 0.001) and BMI decreased by 1.2 kg/m2 (p < 0.001). Hemoglobin A1c decreased by 0.6 mmol/mol (p = 0.0014), insulin requirement reduced by 7 units/day (p = 0.02), and there was no change in additional antidiabetic medications. GLP1RA and SGLT-2 inhibitors are tolerated in transplant patients and result in weight loss and better glycemic control. They are promising agents to treat recurrent or de-novo liver allograft steatosis, but further research is needed to evaluate long-term outcomes in liver transplant recipients.

Vaccine-Preventable Illness Leads to Adverse Outcomes in Liver Transplant Recipients.

Liver transplant recipients (LTR) and patients with chronic liver disease (CLD) are at an increased risk of infections. The objective of our study was to assess the incidence, and impact of vaccine preventable illness (VPI) on outcomes in LTR. National Inpatient Sample (NIS) 2016-2020 was used to identify adults (age > 18) hospitalized LTR using ICD-10 codes. Data were collected on patient demographics, hospital characteristics, etiology of liver disease, hepatic decompensations and outcomes. Patients were stratified into two groups based on the presence or absence of VPI. Multivariate logistic regression analysis was performed to identify the association between VPI and outcomes. Out of 170,650 hospitalized LTR, 13.5% of the patients had VPI. The most common VPI was noted to be influenza (10.7%), followed by pneumococcal infection (2.7%). Incidence of mortality (6.9% vs. 1.6%, p < 0.001), ICU admissions (14.3% vs. 3.4%, p < 0.001), and acute kidney injury (AKI) (43.7% vs 37.35%, p < 0.001) was higher in the VPI group. More than 13% of the LT hospitalizations had concomitant VPI. VPI in LTR was associated with worse outcomes. Our data suggests the need to identify factors associated with reduced vaccination rates and identify strategies to improve vaccination rates and responses in these patients.

Short-Term and Long-Term Effects of Ischemic Conditioning on Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Although liver transplantation (LT) is one of the definitive treatments for patients with end-stage liver failure, it inevitably results in ischemic reperfusion injury. It is known that prognosis is improved when temporary ischemic conditioning (IC) is applied to patients with ischemic reperfusion injury. The objective of this meta-analysis was to determine the short-term and long-term effects of IC on the clinical outcomes of LT recipients. Randomized controlled studies on IC in patients with LTs were included. Patients were compared between an IC group and a sham group. Studies were retrieved from PubMed, Embase, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. Mortality, graft function, and major complications were synthesized using RevMan 5.4.1. Among 316 papers, 17 articles (1196 patients) were included. There was an insignificant increase in short-term mortality (risk ratio [RR]: 3.00, 95% CI: 0.32-28.14, P=.34). However, long-term mortality was lower in the IC group than in the sham group, but not significantly (RR: 0.75; 95% CI: 0.47-1.20, P=.23). Short-term graft function (acute graft rejection and primary graft non-function) was not improved by IC. One-year graft loss tended to show better results in the IC group (RR: 0.53, 95% CI: 0.26-1.07, P=.08). Ischemic conditioning did not have a beneficial effect on LT. Although long-term outcomes appear to be better in the IC group than in the sham group, further randomized controlled trials are needed.

Clinical characteristics and outcomes of liver transplant recipients infected by Omicron during the opening up of the dynamic zero-coronavirus disease policy in China: A prospective, observational study

We analyzed the characteristics, risk factors, outcomes, and post–coronavirus disease 2019 (COVID-19) symptoms in liver transplant recipients in China’s late 2022 COVID-19 wave. Recipients with COVID-19 were enrolled from December 1, 2022, to January 31, 2023, and followed up until May 31, 2023. Baseline and characteristic data were collected. A total of 930 recipients were included, with a vaccination rate (non-mRNA) of 40.0%. Among 726 (78.1%) recipients with COVID-19, 641 (88.3%) patients were treated at home, 81 (11.2%) patients required hospitalization in general wards, 4 (0.6%) patients required intensive care, and 1 (0.1%) patient died because of COVID-19. Severe acute respiratory syndrome coronavirus 2 infection was related to close contact with confirmed cases (P < .001) and the condition of end-stage kidney disease (P < .046). Older age, male sex, less vaccination, and hypertension were independent risk factors for hospitalization. Fatigue (36.9%) was the most common symptom post-COVID-19, followed by memory loss (35.7%) and sleep disturbance (23.9%). Two doses of vaccines had a protective effect against these post-COVID-19 symptoms (P < .05). During this Omicron outbreak, liver transplant recipients were susceptible to COVID-19, with frequent hospitalization but low mortality. Two doses of non-mRNA COVID-19 vaccines could protect against liver transplant recipient hospitalization and post-COVID-19 symptoms.

A Comprehensive Review of Liver Allograft Fibrosis and Steatosis: From Cause to Diagnosis.

Despite advances in posttransplant care, long-term outcomes for liver transplant recipients remain unchanged. Approximately 25% of recipients will advance to graft cirrhosis and require retransplantation. Graft fibrosis progresses in the context of de novo or recurrent disease. Recurrent hepatitis C virus infection was previously the most important cause of graft failure but is now curable in the majority of patients. However, with an increasing prevalence of obesity and diabetes and nonalcoholic fatty liver disease as the most rapidly increasing indication for liver transplantation, metabolic dysfunction-associated liver injury is anticipated to become an important cause of graft fibrosis alongside alloimmune hepatitis and alcoholic liver disease. To better understand the landscape of the graft fibrosis literature, we summarize the associated epidemiology, cause, potential mechanisms, diagnosis, and complications. We additionally highlight the need for better noninvasive methods to ameliorate the management of graft fibrosis. Some examples include leveraging the microbiome, genetic, and machine learning methods to address these limitations. Overall, graft fibrosis is routinely seen by transplant clinicians, but it requires a better understanding of its underlying biology and contributors that can help inform diagnostic and therapeutic practices.

Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing

Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.

Postoperative alterations in ventriculoarterial coupling are an indicator of cardiovascular outcomes in liver transplant recipients.

Liver transplantation (LT) increases the heart and vessel workload in patients with cirrhotic cardiomyopathy. While the interaction of the left ventricle (LV) with the arterial system (ventriculoarterial coupling, VAC) is a key determinant of cardiovascular performance, little is known about changes in VAC after LT. Therefore, we evaluated the relationship between VAC after LT and cardiovascular outcomes. 344 consecutive patients underwent echocardiographic assessments before and within 30 days after LT. Non-invasive arterial elastance (Ea), LV end-systolic elastance (Ees), and LV end-diastolic elastance (Eed) were calculated. The postoperative outcomes included the development of major adverse cardiovascular events (MACE) and the length of stay in the intensive care unit and hospital. A total of 240 patients were included in the analyses. After LT, Ea increased by 16% (P < 0.001), and Ees and contractility index of systolic velocity (S') increased by 18% (P < 0.001) and 7% (P < 0.001), respectively. The Eed increased by 6% (P < 0.001). The VAC remained unchanged (0.56 to 0.56, P = 0.912). Of these patients, 29 had MACE, and those with MACE had significantly higher postoperative VAC. Additionally, a higher postoperative VAC was an independent risk factor for a longer postoperative hospital stay (P = 0.038). These data suggest that ventriculoarterial decoupling is associated with poor postoperative outcomes after LT.