Liver Transplant Patients Research Articles

HPB SO76 - Is there a difference in liver transplant outcomes between daytime vs nighttime transplants?

Abstract Background Liver transplantation (LT) is the most effective treatment for end-stage liver disease. Night-time transplantations are often scheduled to minimize cold ischemia time (CIT), but they may pose challenges due to potential fatigue and circadian rhythm disruptions among surgical teams. This study aims to investigate the effect of transplant timing on the outcomes of liver transplant patients. Method A preliminary retrospective analysis was conducted on liver transplants performed between January and May 2018. Surgeries were categorized into daytime (8:00 am–8:00 pm) and nighttime (8:00 pm–8.00 am) groups. Outcomes examined included operative time, early mortality, complications (wound, vascular, biliary, and other) occurring within 30 days post-surgery, CIT, re-transplantation, length of ITU stay and length of hospital stay. Results The nighttime group, the mean recipient age was 50.17 years (SD 10.86). Surgery duration averaged 5.67 hours (SD 1.57) with a mean CIT of 8.08 hours (SD 2.41). The average hospital stay was 14days, with 1-year and 3-year survival rates of 100% and 95.68%. Acute rejection occurred in 8.7% of patients. The daytime group, the mean recipient age was 51.83 years (SD 10.86). Surgery duration averaged 5.05 hours (SD 1.20) with a mean CIT of 7.31 hours (SD 1.97). Hospital stays averaged 12.88days, with 1-year and 3-year survival rates of 97.2% and 91.67%. Acute rejection occurred in 13.9% of patients. Conclusion The preliminary results suggest slight differences in outcomes between the two groups, but a larger cohort of patients needs to be analyzed to determine statistical significance. This study will be expanded to include 400 transplant patients for a more comprehensive analysis.

Abstract 4117834: Utility of Abdominal Aortic Calcification Assessment for the Prediction of Major Adverse Cardiovascular Events in Liver Transplant Patients

Background: Cardiovascular disease is a leading cause of postoperative morbidity and mortality following liver transplantation (LT). Presence of abdominal aortic calcification (AAC) has been linked to cardiovascular events in the general population. We investigated whether AAC on pre-transplant computed tomography (CT) predicts major adverse cardiovascular events (MACE) post-LT. Methods: Consecutive LT patients between 2010-2018 from the Victorian Liver Transplant Unit (Australia) were included. Extent of AAC was quantified in a blinded fashion, with high AAC defined as a calcium score of ≥500. MACE was defined as any recorded episodes of acute coronary syndrome (ACS), ventricular arrhythmia, decompensated heart failure, or stroke. The primary outcome was post-LT MACE at 30 days and the secondary outcome was all-cause mortality at maximal follow-up. Results: Of 461 patients undergoing LT, 350 had suitable CTs for analysis, of which 90 (25.7%) had also undergone CT coronary angiography. High AAC was identified in 98 patients (28.0%). This finding demonstrated a moderate correlation with high coronary artery calcium score (CACS) ≥400 (r=0.52, p<0.001). Fifty-eight MACE occurred in 42 patients (12.0%) within 30-days. High AAC was associated with increased risk of 30-day MACE (OR=2.68 (95%CI 1.39-5.17), p=0.004), and long-term mortality (HR=2.52 (95%CI 1.29-4.92), p=0.007) at a median follow-up of 4.0 years. In addition, high AAC predicted an increased risk of ACS (OR 3.80 (95%CI 1.18-12.27), p=0.025), heart failure (OR 3.07 (95%CI 1.21-7.80), p=0.020) and atrial fibrillation (OR 2.04 (95%CI 1.02-4.07), p=0.048), with a trend to increased prevalence of ventricular arrhythmia (OR 2.67 (95%CI 0.84-8.50), p=0.10). Following multivariate analysis, high AAC remained a strong independent predictor of MACE (OR=3.49, 95%CI 1.21-10.06, p=0.021). Addition of AAC to the revised cardiac risk index (RCRI) improved model fit for predicting MACE (net reclassification improvement of 52.7% (p<0.001)). Conclusions: This study demonstrates for the first time that high AAC on routine abdominal CT scans is associated with a 3-fold increased risk of 30-day MACE post-LT, and improves cardiovascular risk prediction compared to traditional risk scores. Quantification of AAC may offer a simple method of improving cardiovascular risk assessment and implementation of preventative strategies in liver transplant patients, using pre-existing scans without additional cost or patient risk.

A Novel Preoperative Classification System for Selecting Suitable Surgeries in Liver Transplant Patients with Portal Vein Cavernous Transformation

Background To evaluate the new preoperative Changgung classification (CC) system of portal vein thrombosis (PVT) in choosing suitable operative procedures to reconstruct portal veins during liver transplantation (LT) in patients with portal vein cavernous transformation (PVCT). Methods This retrospective observational study analyzed data from allograft LTs performed for various liver diseases Results The study included 22 males and 4 females with LT indications comprising cirrhosis (n = 9), hepatocellular carcinoma (n = 12), PVCT (n = 2), liver failure from fulminant hepatitis B (n = 1), dysfunction of transplanted liver (n = 1), and chronic rejection of transplanted liver (n = 1). Patients were classified according to Yerdel (21 Yerdel II and 5 Yerdel III) and CC (C1–C5). In total 16 simple operations were performed on C1–C3 cases and 9 complex operations on C4–C5 cases, with one additional simple operation. The distribution according to the Yerdel classification was 16 simple and 5 complex operations in Yerdel II cases and 1 simple and 4 complex operations in Yerdel III cases. The median follow-up time was 27.5 months with overall one-year and three-year OS rates of 88.1% and 83.9% for the cohort. Specifically, the one-year OS rates for patients classified as C1-3 vs. C4-5 were 93.3% and 80.0%, while the three-year OS rates were 86.7% and 80.0%, respectively (p = 0.526). Conclusion The CC proposed in this study shows comparable potential to the Yerdel classification in preoperatively identifying the need for complex surgical techniques in LT patients with PVCT and may also have predictive power for the survival benefits following LT.

Fibrinogen concentrate use in the operating theatre at a quaternary hospital in Australia

AbstractAt our quaternary teaching hospital in Queensland, Australia, there has been a rapid increase from 2019 to 2022 in the usage of fibrinogen concentrate (FC) in preference to cryoprecipitate for cardiac surgery. FC is indicated for patients having major trauma requiring haemostatic resuscitation, major intraoperative haemorrhage, or liver transplant patients with major intraoperative haemorrhage. These patients must exhibit severe hypofibrinogenaemia, which is assessed using assay cut‐offs of thromboelastogram (TEG) (citrated functional fibrinogen [CFF] ≤ 10 mm) or rotational thromboelastometry (ROTEM) (FIBTEM A5 ≤ 8 mm). FC usage over cryoprecipitate for cardiac surgery is an ongoing debate due to advantages such as dose predictability, rapid reconstitution, viral inactivation, and minimal transfusion‐related adverse events; however, it is expensive. The aim of this study was to capture prescribing patterns of FC and appropriateness against local guidelines. Retrospective data were analysed, and the practice was compared to hospital guidelines. Data from 52 patients over a 4‐year period (2019–2022) showed intraoperative haemorrhage was the leading indication for FC use (65%, n = 34), followed by liver transplantation (27%, n = 14), and major trauma (8%, n = 4). When breaking down the cause of intraoperative haemorrhage, cardiothoracic surgery, both elective (50%, n = 17) and emergency procedures (41%, n = 14), accounted for 91% of all operative bleeding requiring FC. There were 34 (65%) of 52 patients who received a differing dose of FC compared to what was recommended in the hospital guideline, with 50% (n = 17) receiving a higher than recommended dose and 50% (n = 17) receiving lower than recommended doses. This project was exempt due to the local policy requirements that constitute research by the Metro South Human Research Ethics Committee (Reference no: CM2305202303). The justification for this exemption was as follows: the study presented no foreseeable risk of patient harm as it involved evaluation of standard care involved the use of existing non‐identifiable patient records.

Impact of physical activity on physical function and quality of life after liver transplantation

Introduction and aim of the study: Liver-related diseases are very common in our society, and as a result, the number of people requiring liver transplantation is likewise increasing. In our research, we intended to analyze the topic of increasing survival rates and improving comfort along with the quality of life while waiting for a transplant, as well as in the postoperative period. We determined that we would investigate the impact of physical activity on risk factors that increase hospitalizations after surgery and decrease quality of life. We summarized the effect and type of exercise on sarcopenia, frailty, and their direct relation to the pre- and post-operative period of liver transplantation. In addition, we analyzed possible obstacles and difficulties arising from the implementation of physical activity in liver transplant recipients. Materials and methods: The authors conducted an extensive review of articles available in PubMed, Google Scholar, UpToDate, Science Direct, and Cochrane databases. The keywords liver transplantation, physical activity, quality of life, sarcopenia, and frailty were the basis of the review. Studies published between 2001 and 2024 were included in the review. Results: The vast majority of the studies emphasized the positive effects of exercise, particularly aerobic and resistance training, on improving the clinical conditions and well-being of liver transplant patients. The papers with inconsistent results nevertheless underscored the need to delve further into this topic. Thus, the overall evidence supports the inclusion of physical exercise in post-transplant care as a key strategy for improving health and quality of life. Conclusion: Regular physical activity is beneficial for clinical outcomes and patients’ quality of life after liver transplantation.

Advancements in MELD score and its impact in Hepatology.

There continues to be an ongoing need for fair and equitable organ allocation. The Model for End-stage Liver Disease (MELD) score has evolved as a calculated framework to evaluate and allocate patients for liver transplantation objectively. The original MELD score has undergone multiple modifications as it is continuously scrutinized for its accuracy in objectively representing the clinical context of patients with liver disease. Several refinements and iterations of the score have been developed, including the widely accepted MELD-Na score. In addition, the most recent updated iteration, MELD 3.0, has been created. The MELD 3.0 calculator incorporates new variables such as patient sex and serum albumin levels and assigns new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is anticipated that the use of MELD 3.0 scores will reduce overall waitlist mortality and enhance access for female liver transplant candidates. However, despite the emergence of the MELD score as one of the most objective measures for fair organ allocation, various countries and healthcare systems employ alternative methods for stratification and organ allocation. This review article highlights the origins of the MELD score, its iterations, the current MELD 3.0, and future directions for managing liver transplantation organ allocation.

Studying the association between single nucleotide polymorphisms of metabolizing enzymes and the therapeutic serum levels of calcineurin inhibitors in Egyptian liver transplant patients

BackgroundMany clinical variables might impact the pharmacokinetics of calcineurin inhibitors (CIs). Different alleles of cytochromes P450 (CYP)3A4/5 and drug transporter P-glycoprotein are the main variables. Other variables include relocated type, treatment duration after transplantation, age, sex, dietary consumption, medications used and renal or hepatic impairment. Tacrolimus and cyclosporine are two main CIs extensively used in organ transplantation. Both drugs are metabolized by CYP3A4 and CYP3A5 isoforms, and single-nucleotide polymorphisms in these genes have been displayed to influence CIs pharmacokinetics. Another important gene is the pregnane X receptor (PXR), which manages the statement of a variety of genes including CYP3A4 genes. PXR has a clinical significance in CIs metabolism. The liver is the essential site for CIs metabolism. A decreased clearance with a prolonged CIs half-life was occurred in patients with impaired liver compared with patients with normal liver function. The presence of different genetic and clinical factors that may affect calcineurin inhibitors trough levels will consequently affect their immunosuppressant effect after liver transplantation.PurposeThis study aims to determine the effect of different genetic polymorphisms in CYP3A4 1B rs2740574 and PXR A7635G rs6785049 and other clinical factors that may affect calcineurin inhibitors pharmacokinetics after liver transplantation.ResultsThe presence of T allele in CYP3A4 gene was associated with elevated DATLs with P values of 0.00, 0.00, 0.007 and 0.00 after tacrolimus doses 4, 30, 60 and 90, respectively. Regarding PXR gene, the presence of G allele was associated with elevated DATLs in cyclosporine. About 432 correlations were tested in both drugs. In CYP3A4 genotype CC, male sex was associated with elevated DATLs interpreted by strong positive correlations and statistically significant difference in all DATLs, except DATL 60 (P value 0.374). No strong association was found between low hemoglobin levels and DATLs in almost all the follow-up periods. There were many positive relations between increased total and direct bilirubin and increased DATLs.ConclusionsStudying the various genetics and clinical factors that may affect calcineurin inhibitors serum concentrations is very essential for successful treatment plans after organ transplantation. These different factors may interact with each other and these complicated interactions may complicate the patient’s conditions post-transplantation. Considering all these complicated interactions is very crucial in monitoring treatment plans, especially in the presence of other comorbidities or chronic diseases. More studies with large number of patients should be conducted to explore more consequences of these interacting variables of treatment plans of these patients and all studied parameters in this study should be considered while monitoring patients after transplantation.

Outcomes of Bridging Therapy in Liver Transplantation for Hepatocellular Carcinoma

Background: Liver transplantation (LT) is a method for treating hepatocellular carcinoma (HCC) with satisfactory outcomes. One of the novel methods for predicting LT outcomes is the Metroticket 2.0 model. The disease in patients initially within the Milan criteria (MC) may progress while on a transplantation waitlist; thus, various transplantation bridging therapy (BT) methods are proposed for patients to stay within the MC and optimize the LT outcome. Methods: We performed a retrospective analysis of patients who underwent LT for HCC at an oncological and transplantation center in northern Poland. Patients who underwent (n = 10) or did not undergo (n = 11) BT were included. The primary endpoints of the study were mortality among the patients, HCC recurrence, and Metroticket 2.0 scores based on LT qualification results and explant pathology outcomes. The median follow-up length was 44.03 months. Results: Patients who underwent BT had significantly lower Metroticket 2.0 scores and greater AFP concentrations at baseline. At LT, there was no significant difference in Metroticket 2.0 scores or AFP concentrations between the groups. Explant Metroticket 2.0 scores were significantly lower in patients who received BT. A complete pathologic response was achieved in 30.0% of patients who underwent BT. The recurrence-free survival rates were 100% and 90.91% in patients who underwent and did not undergo BT, respectively. Overall survival was 80.0% and 81.81% in patients who underwent and did not undergo BT, respectively. Conclusions: BT should be considered only as a means of remaining within the LT criteria. Routine BT does not appear to be justified for LT patients.

Personalized CZA-ATM dosing against an XDR E. coli in liver transplant patients; the application of the in vitro hollow fiber system.

A patient with an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM) and oxacillinase (OXA-48) producing Escherichia coli (E. coli) infection was awaiting orthotopic liver transplant. There is no standardized antibiotic prophylaxis regimen; however, in line with the Infectious Diseases Society of America guidance, an antibiotic prophylactic regimen of ceftazidime-avibactam 2.5g TDS with aztreonam 2g three times a day (TDS) IV was proposed. The hollow fiber system (HFS) was applied to inform the individualized pharmacodynamic outcome likelihood prior to prophylaxis. A 4-log reduction in CFU/mL in the first 10 h of the regimen exposure was observed; however, the killing dynamics were slow and six 8-hourly infusions were required to reduce bacterial cells to below the limit of quantification. Thus, the HFS supported the use of the regimen for infection clearance; however, it highlighted the need for several infusions. Standard local practice is to administer prophylaxis antibiotics at induction of orthotopic liver transplantation (OLT); however, the HFS provided data to rationalize earlier dosing. Therefore, the patient was dosed at 24 h prior to their OLT induction and subsequently discharged 8 days after surgery. The HFS provides a dynamic culture solution for informing individualized medicine by testing antibiotic combinations and exposures against the bacterial isolates cultured from the patient's infection. .

Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study.

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.

Immune Checkpoint Inhibitors in the Pre-Transplant Hepatocellular Carcinoma Setting: A Glimpse Beyond the Liver.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has considerably changed, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could not only stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumour that finally permits LT. There are increasing reports of patients that have performed LT after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs, graft rejection might be favoured. In addition, chronic adverse effects affecting other organs may also appear after the end of therapy. This review aims to evaluate the readiness and outcomes of LT in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to LT. While early evidence supports the feasibility of LT following ICIs therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management.

Construction of a Competency Evaluation Indicator System for Specialist Nurses in Liver Transplantation: A Delphi Study.

Liver transplantation specialist nurses provide comprehensive and safe care for liver transplant patients, which requires them to have a wide range of competencies. However, at present, there is no comprehensive understanding of the competency of liver transplantation specialist nurses in China, and there is a lack of comprehensive evaluation indicators. The purpose of this study was to construct a competency evaluation indicator system for specialist nurses in liver transplantation. Utilizing the "Iceberg model" of competency, the indicator system for evaluating the competency of liver transplant specialist nurses was developed through literature review, semi-structured interviews, and two rounds of Delphi expert consultation. Twenty nursing and medical experts in liver transplantation were consulted over two rounds. The effective response rates for the expert consultation questionnaires were 90.91% and 100.00% for the first and second rounds, respectively. The coefficient of expert judgment was 0.920, the coefficient of familiarity was 0.880, and the authority coefficient was 0.900. The value range of the coefficient of variation in the second round was 0.00-0.16, both <0.25, indicating that the degree of coordination of expert opinions was high. The final competency evaluation index system for liver transplant specialist nurses encompassed 6 primary indicators, 17 secondary indicators, and 59 tertiary indicators, including professional knowledge, professional skills, social role, self-concept, personality quality, and motivation. The developed competency evaluation indicator system for liver transplant specialist nurses possesses scientific validity and reliability, offering a reference for the training and assessment of liver transplant specialist nurses.

Profiles of peripheral regulatory T cells forecasts the feasibility of steroid withdrawal after liver transplantation based on cellular thermal modeling

After liver transplantation, steroid therapy is often used to prevent rejection. However, long-term steroid use can lead to serious side effects, therefore, this study aimed to evaluate the feasibility of peripheral regulatory T cell profiles for steroid discontinuation after liver transplantation through cellular thermal modeling and real-time monitoring of intracellular thermodynamics. In this study, cellular thermal modeling techniques were used to simulate the thermodynamic characteristics of peripheral TREgs under different conditions. The dynamic changes of peripheral Treg in liver transplantation animal models were monitored by flow cytometry and molecular biology. Significant changes in peripheral Treg profiles were observed after initiation of steroid therapy, especially in the discontinuation group, and these changes were strongly associated with the restoration of immune homeostasis. Real-time monitoring of the thermodynamic data revealed that peripheral Treg activity showed a specific temperature dependence in the cellular thermal model. Cell thermal modeling combined with real-time monitoring of intracellular thermodynamics provides a new perspective for evaluating the feasibility of peripheral regulatory T cell profiles for steroid discontinuation after liver transplantation. Strengthening the dynamic monitoring of peripheral Treg spectrum provides an important basis for the formulation of personalized immunosuppression strategies, and improves the therapeutic effect and quality of life of liver transplant patients.

Evaluation of Covid-19 risk perception and psychological status of transplant patients

Abstract Background Liver transplant patients are in the more at-risk group in terms of COVID-19 infection and mortality due to both immunosuppressive treatment and underlying chronic diseases. The aim of this study was to evaluate the COVID-19 risk perception, compliance with preventive measures, and psychosocial status of liver transplant patients. Methods This descriptive cross-sectional survey study included 311 patients who underwent liver transplantation between 2002 -2021 and presented to the outpatient clinic for routine controls. Data were collected via a questionnaire administered through face-to-face interviews. The questionnaire form used to collect the data of the study included a demographic and clinical characteristics form, the Short Depression-Happiness Scale, the COVID-19 Prevention Guidelines Compliance Scale, and the COVID-19 Risk Perception Scale. The Mann-Whitney U, the Kruskal-Wallis test and Spearman’s Rho correlation analysis were used in statistical analyses. Results The median age of the transplant patients who participated in the study was 56 (18-76) years. Of the transplant patients, 84.9% stated that they had COVID-19 vaccination. There was a statistically significant, very weak relationship between the scores of the Brief Depression-Happiness Scale and the COVID-19 Compliance with Preventive Measures Scale (r = 0.132; p = 0.02), and a weak, significant relationship in the same direction between the scores of the COVID-19 Compliance with Preventive Measures Scale and the COVID-19 Risk Perception Scale (r = 0.344; p = 0.001). Conclusions The vaccination rates of the patients were high. As the depression status of the patients decreases, their compliance with preventive measures increases, and as their compliance with preventive measures increases, their risk perception increases. Key messages • Since transplant patients are a vulnerable group, their vaccination status is important in terms of mortality risk. • Psychological factors such as depression-happiness scores influence adherence to COVID-19 preventive measures among transplant patients.

Outcome of a Physical Rehabilitation Program on Functionality and Impact on Quality of Life in Postoperative Liver Transplant Patients: A Systematic Review

Objectives: To conduct a systematic review of the literature on the outcomes of a physical rehabilitation program on functionality and identify possible impacts on quality of life in patients after liver transplantation. Methods: Controlled clinical trials and observational studies were selected from the PubMed, SciELO, and BIREME databases that "t the PICO (P – population; I – intervention; C – comparison; O – outcomes) question “what are the bene"ts of a physical rehabilitation program on functionality and quality of life outcomes in patients undergoing liver transplantation?” Studies written in English, Portuguese, and Spanish, published in the last 10 years were selected. After selection, the Physiotherapy Evidence Database (PEDro) scale was used to perform the methodological evaluation of the studies. Results and Discussion: A total of "ve interventionist articles were selected, most of which had good methodological quality. Only one study did not associate resistance training with aerobic exercises, but all had signi"cant results regarding increased functional capacity and reduced perception of fatigue after liver transplantation. Conclusion: !e studies indicated that the association of a resistance training program associated with aerobic training is bene"cial in terms of muscle strength gain, exercise capacity, and perception of fatigue.

Influence of recipient KRAS gene rs712 polymorphisms on the overall survival rate of hepatocellular carcinoma after hepatic transplantation

Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between KRAS rs712 polymorphism and HCC. However, the relationship between KRAS rs712 polymorphism and HCC recurrence after LT remained unclear. A total of 93 HCC patients who underwent LT from March 2008 to Dec 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as KRAS rs712. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The KRAS rs712 genotype frequencies were determined using the Χ2 test and the minor allele frequencies (MAFs) of KRAS rs712 genotypes were calculated by Hardy–Weinberg equilibrium. We found that the recipient KRAS rs712 polymorphism was significantly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and recipient KRAS rs712 genotype were proved to be independent risk factors for HCC recurrence after LT. Patients with donor TG/TT genotypes had a significantly higher RFS and OS than TT genotype. The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation.

Effect of donor GSTM3 rs7483 genetic variant on tacrolimus elimination in the early period after liver transplantation.

Glutathione S-transferase mu (GSTM) belongs to the group of phase II drug-metabolizing enzymes, and the GSTM1 genetic variant has been reported to have a potential association with the metabolism of immunosuppressive drug after renal transplantation. The effect of donor and recipient GSTMs genetic variants on tacrolimus (Tac) metabolism was the focus of our investigation in this study. A total of 203 liver transplant patients were recruited for the study. In the training set (n=110), twenty-one SNPs in five genes (GSTM1-5) were genotyped by the drug-metabolizing enzymes and transporter (DMET) microarray. CYP3A5 rs776746 and GSTM3 rs7483 were genotyped using a Mass ARRAY platform in the validating set (n=93). Tac C/D ratios of donor GSTM3 rs7483 AA carriers were significantly lower than those with the G allele at weeks 1, 2, 3 and 4 after liver transplantation (LT). Multivariate analysis was conducted on the training set and validating set, donor and recipient CYP3A5 rs776746, donor GSTM3 rs7483 and total bilirubin were identified as independent predictors of Tac C/D ratios in the early period after LT. Combining CYP3A5 rs776746 and donor GSTM3 rs7483 genotypes, Tac C/D ratios were observed to be increasingly lower with increasing numbers of alleles associated with fast metabolism. Moreover, the risk of a supratherapeutic C0 (Tac > 15 ug/L) was significantly higher for poor metabolizers than the other groups at week 1 after LT. There was a significant association between the donor GSTM3 rs7483 genetic variant and Tac metabolism in the early period after LT. Genotype classification might have a better predictive ability of the initial Tac doses.

Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence

Background/Objectives: Neuroendocrine neoplasms (NEN) are heterogeneous entities. Despite considerable advancement in the field, almost 50% of patients have metastatic disease, when liver transplantation (LT) is one of the possible treatments offering a cure in well-selected patients. Methods: The present study aims to systematically review all the literature from 2000 onwards on using LT for patients with NEN-LM, with particular attention to the risk factors of death and recurrence. Results: LT offers 5-year OS ranging from 52 to 74% and 5-year TFS rates ranging from 39 to 62%, with even better results published from 2009 onwards. The main risk factors for patient deaths are related to unfavorable primary tumor pathology, higher liver involvement, and simultaneous LT and primary resection. Similarly, recurrence is higher related to poor tumor grade and differentiation, and in the case of an older recipient age. Conclusions: Applying uniform criteria and a more in-depth understanding of the relevant prognostic factors contribute to a better selection of candidates for curative LT due to NEN metastases. LT for unresectable or liver-restricted NENs has a relevant place in the treatment algorithm and has achieved excellent results in recent decades, but more international efforts are needed to further improve outcomes.

Locoregional Therapies and Interventional Radiology in Managing Hepatocellular Carcinoma: A Comprehensive Approach to Bridging, Downstaging, and Liver Transplantation

AbstractHepatocellular carcinoma (HCC) remains a significant global health challenge, particularly for patients awaiting liver transplants (LTs) due to the scarcity of donor organs. During the waiting period, a multidisciplinary approach becomes crucial to optimize tumor treatment and preserve liver function. In recent years, interventional radiology has emerged as an integral part of treatment strategies. It has played a pivotal role in bridging and downstaging patients on the path to transplantation. Interventional radiologists administer minimally invasive locoregional therapies to HCC patients on LT waiting lists. Additionally, they address complications such as portal hypertension and portal vein thrombosis, which can lead to clinical deterioration and jeopardize transplant candidacy. This article examines the pivotal role of interventional radiology in the management of HCC, highlighting recent studies and advancements within the field. Additionally, it provides a concise review of the eligibility criteria for LT in patients with HCC, alongside a discussion of the surgical techniques employed in LT for these patients.

Early Prediction of Acute Kidney Injury in Living Donor Liver Transplantation by Serum Cystatin C Concentration at the End of the Surgery.

Acute kidney injury (AKI) is a prevalent complication of liver transplantation, leading to prolonged hospital or intensive care unit stay and significant morbidity. Recently, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have been investigated for their potential role in the early detection of AKI in liver transplantation patients. Our study comprised 60 patients with end-stage liver disease undergoing living donor liver transplantation. Based on the postoperative development of AKI, the patients were categorised into two groups: the AKI group comprising 22 patients and the non-AKI group comprising 38 patients. Serum cystatin C and urine NGAL levels were measured twice: immediately after induction of anaesthesia (baseline) and at the end of the surgery. The overall incidence of AKI was 36.66%. The mean cystatin C level measured at the end of the surgery was significantly higher in the AKI group (1.12 ± 0.40 mg/L) than in the non-AKI group (0.82 ± 0.27 mg/L) [P = .001]. The receiver operating characteristic curve for the postoperative cystatin C biomarker demonstrated a significant difference between the AKI and non-AKI groups [area under the curve: 0.71, P = .007]. However, baseline cystatin C and urine NGAL levels did not significantly differ between the groups. Cystatin C levels measured at the end of the surgery showed a better predictive value and higher accuracy in identifying post-liver transplantation patients with AKI than baseline cystatin C and urine NGAL.