Liver Transplant Patients Research Articles

Perioperative Fluid Management in Paediatric Liver Transplantation: A Systematic Review.

Perioperative fluid management remains a challenging aspect of paediatric liver transplantation (LT) because of the risk of postoperative complications and haemodynamic instability. Limited research has specifically investigated the impact of fluid management and transfusion on mortality and morbidity in pediatric LT patients. This systematic review summarizes the evidence regarding perioperative fluid management and its clinical outcomes in paediatric LT patients. All primary studies published in English evaluating perioperative fluid management in paediatric LT patients were eligible. PubMed, EBSCOHost, Embase, Proquest, and Google Scholar databases were searched from inception to December 19, 2023. Risks of bias were assessed using the Joanna-Briggs Institute checklist. The results were synthesized narratively. Five retrospective cohort studies of good-excellent quality were included in this review. Two studies evaluated intraoperative fluid administration, one study compared postoperative fluid balance (FB) with outcomes, and two studies compared massive versus non-massive transfusion. A higher mortality rate was associated with intravenous lactated ringer's (LR) than with normal saline, but not with massive transfusion (MT). Longer hospital stays were correlated with MT, >20% positive FB in the first 72 hours, and greater total intraoperative blood product administration. Higher intraoperative fluid administration was associated with a greater thrombotic risk. Additionally, intraoperative MT and lR infusion were associated with an increased risk of 30-day graft loss and graft dysfunction, respectively. Fluid management may impact the outcomes of paediatric LT recipients. These findings underscore the need for more studies to explore the best fluid management and evaluation strategies for children undergoing LT.

HHV-6 Infection Complicated by Viral Encephalitis Following Liver Transplantation: A Case Report

Abstract Human herpesvirus 6 (HHV-6) is a significant pathogen following solid organ transplantation. Here, we report on a 64-year-old female with cirrhosis related to non-alcoholic fatty liver disease who underwent orthotopic allogeneic liver transplantation and was ultimately diagnosed with HHV-6 encephalitis through cerebrospinal fluid analysis and MRI. Empirical treatment with daily ganciclovir was initiated according to characteristics indicative of viral encephalitis 3 days before confirmed diagnosis. Subsequent improvement in symptoms was observed, with clearance of HHV-6 from the blood. The complex diagnosis and management of this case accentuates the possibility of serious consequences of HHV-6 infection in postoperative liver transplant patients. Clinicians must maintain a high index of suspicion for HHV-6 reactivation, especially given its association with immunosuppressive drug regimens. Prompt recognition and initiation of antiviral therapy are paramount, particularly when patients present with fever or psychiatric symptoms, as these may indicate HHV-6 encephalitis.

Goal-Directed Use of Prothrombin Complex Concentrates in Liver Transplantation: Is a Plasma-Free Procedure Feasible?

Background: Fresh frozen plasma (FFP) transfusions have been the mainstay of hemostatic intervention for the treatment of bleeding and coagulation abnormalities arising during liver transplantation (LT) for decades. However, numerous clinical studies showed that FFP has many side effects, including the risk of pathogen transmission, transfusion-associated circulatory overload (TACO), transfusion-related immunomodulation (TRIM), and transfusion-related acute lung injury (TRALI). These adverse events are particularly challenging in patients undergoing LT, who often suffer from severe portal hypertension, poor renal function and coexisting cardiac disease.The aims of this review are to summarize the pharmacological properties of currently available PCCs, to represent the theoretical benefits and the possible risks related to the use of these drugs in patients undergoing LT, and, finally, to review the current literature on the topic in order to highlight the evidence that currently supports PCC use in LT patients. Methods: The current literature on the topic was reviewed in order to highlight the evidence that currently supports PCC use in LT patients. Results: Prothrombin complex concentrates (PCCs) may offer several advantages when compared to FFP. Indeed, PCCs have been shown to reduce the risk of TACO, which during liver transplantation may deteriorate portal hypertension, increase intraoperative bleeding, and possibly reduce survival rates. One of the major concerns for PCC use is thrombogenicity. However, currently available PCCs are much safer as they contain inactivated forms of the vitamin K-dependent coagulation factors and protein C, protein S, antithrombin and/or heparin. Nowadays, the use of PCCs to correct coagulation abnormalities that occur during LT is an increasingly widespread practice. However, it is not yet clear what level of evidence supports this practice, and what the risks associated with it are. Conclusions: Administration of PCC in LT patients to correct haemostatic abnormalities seems to be well-tolerated, but the relationship between PCC use and thromboembolic events in the postoperative period remains unclear. Adequately powered, methodologically sound trials are urgently required for more definitive conclusions about the efficacy and safety of PCCs in a broad phenotype of LT recipients.

Sirolimus to treat chronic and steroid-resistant allograft rejection-related fibrosis in pediatric liver transplantation.

This study aimed to report our experience with the use of sirolimus in pediatric liver transplant patients with chronic rejection or steroid-resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off-label treatment with sirolimus for chronic ductopenic rejection or cortico-resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1-month after postsirolimus introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue sirolimus treatment owing to nephrotic proteinuria. In conclusion, sirolimus may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

Serum from patients with cirrhosis undergoing liver transplantation induces permeability in human pulmonary microvascular endothelial cells ex vivo.

Patients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells ex vivo. Adults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture was assessed by transendothelial resistance measured using the ECIS ZΘ system. Confluent cells from two different endothelial cell donors were stimulated with human serum from liver transplant patients. Pooled serum from healthy men and purified inflammatory agonists served as controls. The permeability response to serum was quantified as the area under the normalized resistance curve. Responses were compared between time points and analyzed for associations with clinical characteristics of liver transplant patients and their grafts. Liver transplant sera from all time points during surgery-induced permeability in both endothelial cell lines. The magnitude of permeability change was heterogeneous between patients, and there were differences in the effects of sera on the two endothelial cell lines. In one of the cell lines, the severity of liver disease was associated with greater permeability at the start of surgery. In the same cell line, serum collected 15 min after liver reperfusion induced significantly more permeability as compared to that collected at the start of surgery. Early postreperfusion sera from patients undergoing living donor transplants induced more permeability than sera from deceased donor transplants. Sera from two exemplary cases of patients on preoperative dialysis, and one patient with an unexpectedly long warm ischemia time of the liver graft, induced exaggerated and prolonged endothelial permeability. Serum from patients with cirrhosis undergoing liver transplantation induces permeability of cultured human pulmonary microvascular endothelial cells. Increased endothelial permeability during liver transplantation may contribute to organ injury and present a target for future therapeutics.

Impact of Serum IL 10 on Early Prediction of Allograft Rejection in Liver Transplantation

Abstract Background Tissue transplantation is the preferred treatment for end organ failure such as heart, lung, kidney and liver. Unless the donor and recipient of a transplant are genetically identical, the donated tissue is viewed by the immune system of the recipient as non-self. multiple cytokines are involved in this process, however little is known about their predictive role in rejection. IL10 which exhibit anti-inflammatory activity could be used as early predictor of acute rejection. Objective The aim of the current study is to evaluate the possible association between serum IL10 level in liver transplant patients and acute allograft rejection. Patients and Method: This study was conducted on 45 subjects. Patients will be followed up for 2months and they will be further divided into two groups: Those who developed early acute rejection and those who did not develop rejection (controls) Result The study included 38 patients did not develop rejection and 7 patients developed rejection. We found unchanged during rejection of the LT of the levels of IL-10 Conclusion Several studymust be conducted on cytokines on large sample size to prove early prediction of acute rejection

The Effect of Enhanced Recovery After Surgery Protocol on Surgical Site Infections in Liver Transplantation.

Background: Liver surgeries are treatment modalities that require careful pre- and postoperative follow-up for both the surgeon and the patient. Infections are the leading causes of morbidity and mortality after liver transplantation. Infections are the most frequent cause of death between 30 and 180 days after liver transplantation. We aimed to investigate the effect of the Enhanced Recovery After Surgery (ERAS) protocol on the prevention of infections in liver transplant patients. Patients and Methods: The study included patients who underwent liver transplantation in Ataturk University Organ Transplantation Center between 2017 and 2022. Two patient groups with and without ERAS were formed. Blood and urine cultures were collected retrospectively, and those with positive blood cultures for bacteremia were recorded as infection development. The development of infection between the two groups was statistically compared. Also, all patients' length of intensive care stay, length of hospital stay, and duration of antibiotic use were recorded. These parameters were compared between both groups. Results: There was a statistically significant difference between the two groups in terms of infection development (p: 0.01). There was a statistically significant difference between the two groups in terms of duration of antibiotic use and length of hospital stay (Mann-Whitney U test; p: 0.00, p: 0.04, respectively). There was no statistically significant difference between the two groups in terms of length of intensive care stay. Conclusion: We concluded that the introduction of an ERAS protocol was associated with fewer infections, thus shortening the duration of antibiotic therapy and length of hospital stay, although the standardization of the protocols is difficult, especially in liver transplants.

Preoperative Evidence-Based Practice for Prevention of Early Postoperative Infections in Patients Receiving a Liver Transplant.

BACKGROUND This study aimed to evaluate the effectiveness of implementing evidence-based preoperative nursing interventions in reducing postoperative infections and intensive care unit (ICU) length of stay among liver transplant recipients. MATERIAL AND METHODS A controlled study was conducted, comparing postoperative outcomes between an intervention group receiving standardized, evidence-based preoperative care and a control group receiving routine preoperative care. Patients undergoing elective liver transplantation from September 2020 to March 2021 were included and assigned to either the intervention or control group. The intervention group received preoperative interventions based on best available evidence, while the control group received standard preoperative care. The primary outcomes measured were postoperative infection rates and length of ICU stay. RESULTS In the control group the overall Intensive Care Unit (ICU) length of stay was 3 days and the infection rate was 33.30%, while in the intervention group it was 3 days and 13.80% (P<0.05). There was no significant difference in the length of ICU stay between the control and the intervention groups (P>0.05). There was a significant improvement in the awareness, acceptance, and compliance of doctors and nurses. CONCLUSIONS Using the best evidence-based intervention for preoperative nursing of liver transplantation patients can standardize preoperative nursing behavior. Although we did not find significant differences in outcomes before and after the intervention, it is necessary to prevent postoperative infection and improve nursing compliance.

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

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

Detection of Anti-Strongyloides Antibodies in the Serum of Liver Transplant Recipients: Need of Screening for This Neglected Helminthiasis.

Immunosuppressed patients, particularly transplant recipients, can develop severe strongyloidiasis. This study aimed to detect anti-Strongyloides IgG antibodies in a panel of sera from liver transplant patients. Two techniques were used: ELISA as the initial screening test and Western blotting as a confirmatory test. ELISA reactivity of 10.9% (32/294) was observed. The 40-30 kDa fraction was recognised in 93.7% (30/32) of the patients, resulting in a positivity rate of 10.2%. These data highlight the importance of serological screening for Strongyloides stercoralis infection in liver transplant recipients.

Postoperative Care and Outcomes in Solid-Organ Transplant Patients Undergoing Lower Extremity Fracture Treatment.

To determine the postoperative outcomes in solid-organ transplant (SOT) patients undergoing operative treatment of lower extremity fractures. Retrospective comparative study. Academic Level 1 trauma center. Patients who underwent SOT and operative treatment of lower extremity fracture from 2013 to 2021 were identified, excluding pathologic fractures. Postoperative complications, length of stay, time to death, 90-day and 1-year readmission rates, readmission causes, discharge location, and immunosuppressive regiments. Sixty-one patients with an average age of 67 years (range 29-88) were included. The mortality rate was 37.7%. The average follow-up was 15.2 months (range of 2 weeks-10 years). The majority of patients (32.8%) had received a liver transplant, and femoral neck fractures constituted the largest fracture group. The average length of stay was 10 days, with the shortest being 1 day and the longest being 126 days (SD 18). The majority of patients (57.3%) were not discharged home. Only 2 suffered from a postoperative complication requiring another procedure: hardware removal and liner exchange for periprosthetic joint infection, respectively. There was a 27.9% 90-day readmission rate with 2 deaths within that period with the most common being altered mental status (29.4%), genitourinary infections (17.6%), repeat falls (11.8%), and low hemoglobin requiring transfusion (11.8%). The longest average time to death analyzed by transplant type was found among lung transplant patients (1076 days, 62.5% mortality), followed by liver transplant patients (949 days, 35.0% mortality), and then kidney transplant patients (834 days, 38.9% mortality). The shortest time to death was 71 days from index procedure. Family members of SOT patients undergoing operative treatment of lower extremity fractures should be made aware of the high risk for 90-day readmission postoperatively (27.9%) and overall mortality (12.5%). Providers should be aware of the need for multidisciplinary involvement for inpatient care, monitoring postoperative complications, and facilitating discharge planning. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Wogonin Alleviates DCD Liver Ischemia/Reperfusion Injury by Regulating ALOX15/iNOS-mediated Ferroptosis.

Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now suggests that ferroptosis plays a key regulatory role in the development of IRI, so targeting ferroptosis may be an effective strategy to alleviate IRI in liver transplantation (LT). Using donation after circulatory death LT models in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) models in BRL-3A cells, we tested the effect of the Chinese medicine monomer wogonin on liver IRI and explored the specific mechanism. Wogonin attenuated liver IRI and increased the survival rate of rats by inhibiting lipid peroxidation and ferroptosis. Mechanistically, arachidonic acid 15-lipoxygenase-1 (ALOX15) and inducible nitric oxide synthase (iNOS) were identified as potential targets of baicalein through bioinformatics analysis combined with in vivo and in vitro experiments. This result was further confirmed by molecular docking and cellular thermal shift assays. Finally, we silenced ALOX15 and iNOS in the OGD/R cell model and found that silencing ALOX15 and iNOS could reproduce the regulatory effect of wogonin and abrogate the regulatory effect of wogonin. In brief, this study emphasizes that wogonin exerts a protective effect in liver IRI through the regulation of ALOX15- and iNOS-mediated ferroptosis. ALOX15 and iNOS are potential targets for intervention in IRI induced by LT, and wogonin is a drug candidate for LT patients.

Impact of Albumin Infusion Compared With Crystalloid Infusion on Organ Function After Liver Transplantation in Adult Patients

ObjectivesTo compare the clinical benefit of using albumin versus crystalloids for volume resuscitation on organ function in adult patients after liver transplantation. DesignA retrospective cohort study SettingData from a tertiary care facility electronic medical record, (EMR) on liver transplantation patients admitted to the intensive care unit (ICU) PatientsAdults admitted to the ICU after liver transplantation InterventionsCrystalloid fluid resuscitation compared to albumin 5% in the immediate postoperative period after liver transplant. Measurements and main resultsAdults who underwent liver transplantation surgery and received a 5% albumin solution were compared with adults who received a crystalloid solution. Demographic, etiology, clinical variables, perioperative, and outcome variables were collected. The data were analyzed using a t-test, two-way ANOVA, and multivariate analysis. After applying all the exclusion criteria, a conservative population of 57 adult patients who underwent liver transplantation was included in this study. The crystalloid group had 27 patients (47.4%), while the albumin group had 30 patients (52.6%). The total mean age of the population was 52.2 years; males constituted most of the population (52.6%). Patients in the crystalloid group had similar characteristics to those in the albumin group. Daily SOFA scores gradually decreased during the postoperative period in both groups. The trend of the SOFA score was not different between the two groups. A two-way ANOVA shows no statistical difference in SOFA Score between the two groups postoperatively; the p-value is 0.84. A multivariate linear regression analysis shows that the MELD score was a predictor of the 7-day postoperative SOFA score in this population. ConclusionsIn our study, the use of albumin compared to crystalloids in patients undergoing liver transplantation appeared to have no significant difference in terms of the risk of organ dysfunction. However, further research is needed to confirm these findings and fully understand the potential benefits and risks of using either type of fluid.

Risk Factors for Unplanned Readmission in Adult Liver Transplant Patients: A Retrospective Study

IntroductionUnplanned readmission is an important indicator for evaluating medical care quality. Adult liver transplant patients have high risk for readmission, which seriously affects their recovery. As there is currently a lack of research on risk factors for unplanned readmission of adult liver transplant patients in China, the purpose of this study was to elucidate such risk factors. MethodsData for patients undergoing liver transplantation surgery at a tertiary hospital in Zhejiang Province from March 2018 to July 2022 were retrospectively collected. Patients were divided into readmission and nonreadmission groups based on whether unplanned readmission occurred within 90 days. Univariate analysis and logistic regression were used to analyze risk factors for unplanned readmission. ResultsIn total, 123 adult liver transplant patients were included; 38 had unplanned readmission, for a rate of 30.8%. There was a statistically significant difference between the groups in terms of age, educational level, operation time, intraoperative bleeding volume, number of complications, postoperative hospital stay, and hemoglobin (P < .05). Logistic regression analysis showed that age [OR = 1.085, 95% CI (1.022, 1.152)], operation time [OR = 1.010, 95% CI (1.001, 1.020)], postoperative hospital stay [OR = 1.124, 95% CI (1.023, 1.235)], and number of complications [OR = 4.487, 95% CI (1.234, 16.319)] were independent risk factors for unplanned readmission in adult liver transplant patients (P < .05). ConclusionsThe current situation of unplanned readmission for adult liver transplant patients cannot be ignored, indicating that staff should identify risk factors for unplanned readmission as soon as possible and take targeted personalized measures and health education to reduce readmission risk.

Effect of Educational Program on Activities of Daily Living among Post Liver Transplantation Patients.

Effect of Educational Program on Activities of Daily Living among Post Liver Transplantation Patients.

Endoscopic Ultrasound-Guided Liver Biopsy Is Safe and Effective in Post Liver Transplant Patients

Endoscopic Ultrasound-Guided Liver Biopsy Is Safe and Effective in Post Liver Transplant Patients

Association between protein-energy malnutrition and healthcare use among adult patients after liver transplantation: A retrospective cohort study.

Protein-energy malnutrition is associated with poor surgical outcomes in liver transplant patients, but its impact on healthcare use has not been precisely characterized. We sought to quantify the burden of protein-energy malnutrition in hospitalized patients undergoing liver transplantation. Current Procedural Terminology codes were used to identify United States hospitalizations between 2011 and 2018 for liver transplantation using the Nationwide Inpatient Sample. Patients <18 years old were excluded. Protein-energy malnutrition was identified by International Classification of Diseases Ninth and Tenth Revision codes. Multivariable regression was used to determine associations between protein-energy malnutrition and hospital outcomes, including hospital length of stay and hospital charges/costs. Of 9856 hospitalizations, 2835 (29%) had protein-energy malnutrition. Patients with protein-energy malnutrition had greater comorbidity burden and in-hospital acuity (eg, dialysis, sepsis, vasopressors, or mechanical ventilation). The adjusted median difference of protein-energy malnutrition vs no protein-energy malnutrition for length of stay was 6.4 days (95% CI, 5.6-7.1; P < 0.001), for hospital charges was $108,063 (95% CI, $93,172-$122,953; P < 0.001), and for hospital costs was $23,636 (95% CI, $20,390-$26,882; P < 0.001). Among patients undergoing liver transplantation, protein-energy malnutrition was associated with increased length of stay and hospital charges/costs. The additional cost of protein-energy malnutrition to liver transplantation programs was $23,636 per protein-energy malnutrition hospitalization. Our data justify the development of and investment in personnel and programs dedicated to reversing-or even preventing-protein-energy malnutrition in patients awaiting liver transplantation.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors.

Hepatic artery occlusion (HAO) after liver transplantation (LT) is a devastating complication, resulting in early graft loss and reduced overall survival. Ultrasound is an established assessment method for HAO in patients following LT, especially those with complex hepatic artery reconstruction. To investigate the ultrasound characteristics and analyze the risk factors associated with HAO in patients after LT. We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022. Fourteen patients diagnosed with acute HAO (A-HAO) by surgery and fifteen diagnosed with chronic HAO (C-HAO) were included. A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table. All patients underwent an ultrasonography examination. Parameters including resistance index (RI), peak systolic velocity (PSV), and portal vein velocity (PVV) were compared across the groups. Additionally, basic clinical data were collected for all patients, including gender, age, primary diagnosis, D-dimer concentration, total operation time, cold ischemia time, hot ischemia time, intraoperative blood loss and transfusion, intraoperative urine volume, infusion, model for end-stage liver disease (MELD) score, and whether complex hepatic artery reconstructions were performed. Furthermore, risk factors influencing HAO formation after LT were analyzed. Compared to the non-HAO group, PVV and RI were higher in the A-HAO group, while PSV was lower. Conversely, both PSV and RI were lower in the C-HAO group compared to the non-HAO group. The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase (GGT) level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group. However, there were no distinct differences between the two groups in D-dimer, MELD score, pre-occlusion alanine transaminase and aspartate transaminase levels, or intraoperative conditions. Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development. Additionally, complex hepatic artery reconstructions, defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries, constitute a risk factor for A-HAO. Besides, abnormal pre-occlusion GGT elevation is an important biochemical indicator. Therefore, ultrasound examination serves as an important tool for screening HAO, especially in patients with the identified risk factors.

Should Hypervascular Incidentalomas Detected on Per-Interventional Cone Beam Computed Tomography during Intra-Arterial Therapies for Hepatocellular Carcinoma Impact the Treatment Plan in Patients Waiting for Liver Transplantation?

Current guidelines do not indicate any comprehensive management of hepatic hypervascular incidentalomas (HVIs) discovered in hepatocellular carcinoma (HCC) patients during intra-arterial therapies (IATs). This study aims to evaluate the prognostic value of HVIs detected on per-interventional cone beam computed tomography (CBCT) during IAT for HCC in patients waiting for liver transplantation (LT). In this retrospective single-institutional study, all liver-transplanted HCC patients between January 2014 and December 2018 who received transarterial chemoembolization (TACE) or radioembolization (TARE) before LT were included. The number of ≥10 mm HCCs diagnosed on contrast-enhanced pre-interventional imaging (PII) was compared with that detected on per-interventional CBCT with a nonparametric Wilcoxon test. The correlation between the presence of an HVI and histopathological criteria associated with poor prognosis (HPP) on liver explants was investigated using the chi-square test. Tumor recurrence (TR) and TR-related mortality were investigated using the chi-square test. Recurrence-free survival (RFS), TR-related survival (TRRS), and overall survival (OS) were assessed according to the presence of HVI using Kaplan-Meier analysis. Among 63 included patients (average age: 59 ± 7 years, H/F = 50/13), 36 presented HVIs on per-interventional CBCT. The overall nodule detection rate of per-interventional CBCT was superior to that of PII (median at 3 [Q1:2, Q3:5] vs. 2 [Q1:1, Q3:3], respectively, p < 0.001). No significant correlation was shown between the presence of HVI and HPP (p = 0.34), TR (p = 0.095), and TR-related mortality (0.22). Kaplan-Meier analysis did not show a significant impact of the presence of HVI on RFS (p = 0.07), TRRS (0.48), or OS (p = 0.14). These results may indicate that the treatment plan during IAT should not be impacted or modified in response to HVI detection.

Development and validation of individualized tacrolimus dosing software for Chinese pediatric liver transplantation patients: a population pharmacokinetic approach.

We aim to describe the population pharmacokinetics (PPK) of tacrolimus in Chinese pediatric patients under 4years old after liver transplantation and to develop individualized tacrolimus dosing software. A total of 663 blood concentrations from 85 patients aged 4.57months to 3.97years were collected in this study. PPK analysis was performed using a nonlinear mixed effects modeling approach with the software, Phoenix. Using C#, an individualized tacrolimus dosing software was created. The software was then used to predict the concentrations of another ten pediatric liver transplantation patients to verify the accuracy of said software. The predictive error (PE) and the absolute predictive error (APE) for each predicted time point were computed. A one-compartment model with first-order elimination best fitted the data. The apparent volume of distribution (V/F) and apparent clearance (CL/F) were 198.65 L and 2.41 L/h. Postoperative days (POD), total bilirubin (TBIL), and the use of voriconazole significantly influenced tacrolimus apparent clearance. The incorporation of an increasing number of actual blood drug concentrations into the prediction resulted in a decrease in both PE (72%, 17%, 7%) and APE (87%, 53%, 26%). A qualified PPK model of tacrolimus was developed in Chinese pediatric patients. The individualized tacrolimus dosing software could be used as a suitable tool for the personalization of tacrolimus dosing for pediatric patients after liver transplantation.