Factors Associated With Recurrence of Underlying Diseases Among Liver Transplant Recipients: A Single-Center Study.

OBJECTIVES: The recurrence of underlying diseases remains a major cause of graft failure after liver transplant. This study aimed to identify factors associated with the recurrence of underlying diseases and investigate the incidence of these factors and recurrence at the main liver transplant center in Iran. MATERIALS AND METHODS: We included adult liver transplant recipients followed at Shiraz Transplant Center between 2011 and 2018 with a confirmed diagnosis of recurrence of underlying disease in our study. We reviewed medical records and extracted data on demographic characteristics, clinical and paraclinical features, medication use, and current status. We used a systematic random sampling method to select a control group of 95 transplant recipients who did not have recurrence. Of 3022 total transplant recipients, 76 recipients experienced a recurrence of their underlying disease. RESULTS: Model for End-Stage Liver Disease score, underlying disease, recipient blood group, donor sex, donor blood group, and rejection frequency were significantly different between study groups with and without recurrence of underlying diseases. Liver transplant recipients with recurrence had lower mean Model for End-Stage Liver Disease score. Recipients with recurrence also had higher rate of drug consumption (eg, prednisolone, tacrolimus, mycophenolate mofetil, sirolimus). Regression analysis showed that donor sex and rejection frequency had an effect on disease recurrence. Death occurred more frequently in liver transplant recipients with recurrence than in the control group (39.5% vs 26.3%), butthe difference was not significant. CONCLUSIONS: Donor sex and acute rejection frequency are independent factors predictive of the recurrence of underlying disease. Modifying risk factors can help minimize the recurrence of underlying diseases after liver transplant.

Venomous Snakebite Encounters in Liver Transplant Recipients: A Case Report and Review of Relevant Literature.

Envenomation of humans by snakes, a global health challenge, is poorly studied in liver transplant recipients. We report a case of rattlesnake envenomation in a 52-year-old female patient who had previously received a liver transplant to treat nonalcoholic steatohepatitis cirrhosis. Despite stable graft function since her transplant, she exhibited elevated liver enzymes on admission, with a mixed hepatocellular and cholestatic pattern. Treatment included CroFab Crotalidae polyvalent immune Fab (ovine) antivenom and close monitoring, with continuation of her standard immunosuppression regimen. Inpatient observation showed reduced swelling and pain but persistently elevated enzymes. Imaging indicated fatty infiltration with patent hepatic vasculature. Her liver enzymes improved spontaneously, and she was discharged after 5 days, with complete normalization of herliver enzyme levels as shown by repeated laboratory test results 1 month later. Our case emphasizes the risk of graftinjury in liver transplant recipients, as well as the need for vigilant monitoring and early antivenom administration. We urge furtherresearch to establish guidelines for optimal care in this unique population.

Risks of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis After Liver Transplantation.

Biliary complications are common after liver transplantation (LT). Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method to treat biliary complications. Nevertheless, ERCP is not without complications and may have a greater complication rate in the LT population. Knowledge of the prevalence, severity, and possible risk factors for post-ERCP pancreatitis (PEP) in LT recipients is limited. Therefore, this study aims to determine the incidence and severity of PEP and identify potential risk factors in LT recipients. This retrospective cohort included patients ≥18 years who underwent ≥1 ERCP procedures after LT between January 2010 and October 2021. Two hundred thirty-two patients were included, who underwent 260 LTs and 1125 ERCPs. PEP occurred after 23 ERCP procedures (2%) with subsequent mortality in three (13%). Multivariate logistic regression identified wire cannulation of the pancreatic duct as a significant risk factor for PEP (OR, 3.21). The complication rate of PEP after LT in this study was shown to be low and is lower compared to patients without a history of LT. Nevertheless, the mortality rate of this group of patients was notably higher.

[Post liver transplantation complications in pediatric patients in a third level hospital, Lima-Peru, 2016-2020]. / Complicaciones post trasplante hepático en pacientes pediátricos en un hospital de tercer nivel, Lima-Perú, 2016-2020.

OBJECTIVE: determine the complications during the first year after liver transplantation in pediatric patients of the INSN-SB during the period 2016-2020. MATERIALS AND METHODS: Descriptive, cross-sectional study. The medical records of liver transplant patients seen during post-transplant follow-up at the INSN-SB were reviewed, collecting epidemiological characteristics, transplant indication; PELD score, CHILD score and complications prior to the transplant, as well as the frequency of the main complications presented during the first year after the transplant. RESULTS: Of the 16 patients evaluated, 62.5% were under 1 year of age, with a median weight of 7.4kg, 50% presented a CHILD C score, with a median PELD of 23, the main reason for transplantation was atresia of bile ducts (62.5%), the main complications prior to transplantation were portal hypertension (75%) and malnutrition (68.8%). All post-transplant patients presented at least one infectious complication: bacterial (53%), CMV infection (75%) and EBV infection (31%); Regarding vascular complications, 25% presented portal vein thrombosis and one patient (6%) presented hepatic artery stenosis; Regarding biliary complications, 12.5% presented biliary fistula, also 12.5% presented bile duct dilation, while 6.25% presented bilioma. CONCLUSIONS: Among the main complications of the post-liver transplant patient, we can highlight that all patients presented at least one infectious complication (100%), vascular complications in 31% and biliary complications in 31.25% of patients.

Bundle care approach to reduce device associated infections in post-living-donor-liver transplantation in a tertiary care hospital, Egypt.

BACKGROUND: Device-associated infections (DAIs) are a significant cause of morbidity following living donor liver transplantation (LDLT). We aimed to assess the impact of bundled care on reducing rates of device-associated infections. METHODS: We performed a before-and-after comparative study at a liver transplantation facility over a three-year period, spanning from January 2016 to December 2018. The study included a total of 57 patients who underwent LDLT. We investigated the implementation of a care bundle, which consists of multiple evidence-based procedures that are consistently performed as a unified unit. We divided our study into three phases and implemented a bundled care approach in the second phase. Rates of pneumonia related to ventilators [VAP], bloodstream infections associated with central line [CLABSI], and urinary tract infections associated with catheters [CAUTI] were assessed throughout the study period. Bacterial identification and antibiotic susceptibility testing were performed using the automated Vitek-2 system. The comparison between different phases was assessed using the chi-square test or the Fisher exact test for qualitative values and the Kruskal-Wallis H test for quantitative values with non-normal distribution. RESULTS: In the baseline phase, the VAP rates were 73.5, the CAUTI rates were 47.2, and the CLABSI rates were 7.4 per one thousand device days (PDD). During the bundle care phase, the rates decreased to 33.3, 18.18, and 4.78. In the follow-up phase, the rates further decreased to 35.7%, 16.8%, and 2.7% PDD. The prevalence of Klebsiella pneumonia (37.5%) and Methicillin resistance Staph aureus (37.5%) in VAP were noted. The primary causative agent of CAUTI was Candida albicans, accounting for 33.3% of cases, whereas Coagulase-negative Staph was the predominant organism responsible for CLABSI, with a prevalence of 40%. CONCLUSION: This study demonstrates the effectiveness of utilizing the care bundle approach to reduce DAI in LDLT, especially in low socioeconomic countries with limited resources. By implementing a comprehensive set of evidence-based interventions, healthcare systems can effectively reduce the burden of DAI, enhance infection prevention strategies and improve patient outcomes in resource-constrained settings.

The predictors of fungal infections after liver transplantation and the influence of fungal infections on outcomes.

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay.

Crusted Scabies in a Pediatric Liver Transplant Recipient on Immunosuppression.

BACKGROUND Crusted scabies is a severe skin infection resulting from hyper-infestation with the obligate parasite Sarcoptes scabiei var. hominis. In contrast to classic scabies, crusted scabies may involve as many as hundreds to millions of mites. Importantly, this condition is associated with a mortality rate of 60% in 5 years, and is more likely to develop in immunosuppressed hosts, presumably due to an impaired T-cell response against the mite. CASE REPORT We present a case of crusted scabies in a 13-year-old girl during her early post-liver transplant period receiving immunosuppression successfully treated with topical 5% permethrin. She had pruritic erythematous papules, confirmed as scabies through skin scraping. The challenge of misdiagnosis during the initial presentation is noteworthy, given atypical manifestations and more common differentials. To our knowledge, only 2 cases of crusted scabies in pediatric solid-organ transplant recipients have been reported. Despite the absence of guidelines for pediatric solid-organ transplant recipients, urgent treatment is required due to the high associated mortality rates. In our case, early treatment proved successful without any secondary bacterial infections or clinical evidence of relapse during a 6-month follow-up. CONCLUSIONS We report a case of scabies in a pediatric liver transplant recipient that was successfully treated. It is crucial to consider the diagnosis of scabies given the associated morbidity and the risk of secondary bacterial infections among other more common differentials. Notably, the response to standard anti-scabies treatment may lead to resolution without relapse in pediatric solid-organ transplant recipients.

[Liver transplantation program at the Burnasyan Federal Biophysical Center: experience in 500 procedures]. / Programma transplantatsii pecheni v Federal'nom meditsinskom biofizicheskom tsentre im. A.I. Burnazyana: opyt 500 operatsii.

OBJECTIVE: To analyze the features and outcomes of 500 liver transplantations in adults over a 12-year period. MATERIALS AND METHODS: The study included data on 500 liver transplantations between May 2010 and April 2023. We analyzed 483 adults who underwent transplantation and 438 candidates for this procedure. All data were obtained from local liver transplantation registry. Clinical outcomes were recorded as of June 1, 2023. Statistical analysis was performed using the Statistica 12 (StatSoft Inc., USA) and Jamovi version 2.3.21.0 software (Jamovi project). RESULTS: Among 438 patients in the waiting list between January 2012 and May 2023, liver transplantation was performed in 198 (45%) cases including 27 (6%) transplantations from living-related donors and 37 (8%) procedures in other centers. There were 109 (25%) deaths. The 1- and 3-year survival rates were 81% (95% CI 76-85%) and 50% (95% CI 42-59%), respectively. Organs from deceased donors (n=134, 27%) and living-related donors (n=366, 73%) were used for transplantations. Redo transplantations were necessary in 21 (4%) cases. The median age of recipients was 45 years (range 18-72), median MELD-Na score - 16 (range 6-43). The most common indications for transplantation were viral cirrhosis (37%), cholestatic liver disease (16%), and hepatocellular carcinoma (14%). Monotherapy with calcineurin inhibitors was performed in 39% of cases, combination of calcineurin inhibitors and glucocorticoids, antimetabolites or mTOR inhibitors - 52%, three-component schemes - 8% of cases. Annual, 5- and 7-year survival rates of recipients after primary transplantation were 87% (95% CI: 84-90%), 79% (95% CI: 75-83%) and 75% (95% CI: 70-80%), respectively. In case of liver transplantation from living-related donors, these values were 89% (95% CI: 86-92%), 84% (95% CI: 80-88%) and 80% (95% CI: 75-85%), after transplantation from deceased donors - 81% (95% CI: 74-88%), 66% (95% CI: 57-76%) and 58% (95% CI: 45-72%), respectively. CONCLUSION: Liver transplantation is highly effective for patients with diffuse and focal liver diseases. Living donors not only significantly improve availability of this technology, but also provide substantial advantages in outcomes compared to liver transplantation from deceased donors, reducing the likelihood of recipient mortality by 10% after one post-transplantation year and by more than 20% after five years.

Postoperative hypoalbuminemia and outcomes of pediatric liver transplantation.

BACKGROUND: Hypoalbuminemia after liver transplantation (LT) is associated with acute kidney injury (AKI) and poor outcomes in adult LT recipients. This study was performed to examine the association between the postoperative serum albumin level and early postoperative outcomes of LT in children. METHODS: This single-center retrospective review involved pediatric LT recipients (0-18 years old) treated from January 2013 to June 2020. All patients were admitted to PICU and received standard post-LT care protocol. We divided patients into low (< 30 g/L) and normal (> 30 g/L) groups based on postoperative albumin day 1 to 3. RESULTS: Among 108 LT recipients, most had biliary atresia. The median age at the time of LT was 1.8 years [interquartile range (IQR), 1.5-5.7]. There were 18 patients in low albumin group [median albumin level, 27.9 g/L (IQR, 25.8-29.6) and 90 patients in normal albumin group [median albumin level, 34.5 g/L (IQR, 32.4-36.9). The low albumin group had significantly higher incidence of AKI, occurring in 20% of patients with a median onset of 2.5 days following LT (IQR, 1-5). Postoperative hypoalbuminemia (OR, 4.94; 95% CI, 1.32-18.47; p = 0.01) and a longer operative time (OR, 1.37; 95% CI, 1.01-1.47; p = 0.02) were independent risk factors for AKI by multivariable analysis. No significant differences between the two groups were found in other early postoperative outcomes. CONCLUSION: Postoperative hypoalbuminemia was associated with early postoperative AKI following LT in children but not with other worsening outcomes.

Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma.

BACKGROUND: At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM: To develop a model for predicting prognosis after LT in patients with HCC. METHODS: Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS: The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION: The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.

Living donor liver transplantation for patients with portal vein thrombosis: high-volume single center experience.

OBJECTIVE: End-stage liver disease is commonly associated with portal vein thrombosis (PVT). Lastly, PVT is no longer an absolute contraindication for liver transplantation, and many centers adopt portal vein thrombectomy. PVT imposes special technical difficulties during living donor liver transplantation (LDLT). In this research, the experience with PVT cases during LDLT in a high-volume center is introduced. PATIENTS AND METHODS: Between January 2018 and July 2023, 312 patients underwent LDLT. After 88 cases were excluded, 224 cases were included, and their incidence of pre-transplant PVT was 16.5% (37/224). Demographic and clinical features, perioperative variables, and post-transplant outcomes of patients with PVT (PVT group, n=37) were compared to patients who had no PVT (non-PVT group, n=187). RESULTS: According to Yerdel classification, 16, 16, 2, and 3 patients had PVT grade I, II, III, and IV, respectively. Complete venous thrombectomy was accomplished in 34 patients, while for three patients, thrombectomy was not feasible, and graft inflow was established by interposition vascular graft. For portal flow modulation, splenectomy and splenic artery ligation were performed in 7 and 4 patients, respectively, while two patients underwent post-transplant splenic artery embolization. The PVT group had longer operation time (p<0.001), longer warm ischemia time (p=0.031), longer anhepatic phase (p<0.001), and intraoperatively required more than 3 packed RBCs units (p=0.029) and ≥1 platelet unit transfusion (p=0.021) than the non-PVT group. No statistically significant difference was found between groups in terms of re-exploration (p=0.954), post-transplant PVT (p=0.375), biliary (p=0.253) and arterial complications (p=0.593), ICU stay (p=0.633), hospital stay (p=896), and 30-day mortality (p=1.000). Survival analysis showed no statistically significant difference regarding 1-year survival (p=0.176) between both groups. CONCLUSIONS: This study showed that patients with different stages of PVT can successfully undergo LDLT in experienced centers and that they do not differ from patients without PVT in terms of post-transplant complications.

Early Graft Loss With Suspected Seventh-Day Syndrome Following Pediatric Liver Transplantation.

INTRODUCTION: Allograft dysfunction within the first week posttransplant is an uncommon but known complication following liver transplantation. Seventh-Day Syndrome (7DS) is a rare complication of allograft dysfunction following liver transplantation characterized by the rapid clinical deterioration of a formerly well-functioning allograft within the first week posttransplant. The etiology of 7DS is unknown, and treatment options remain limited. While cases of graft survival have been reported, the risk of mortality remains exceedingly high without urgent retransplantation. METHODS: Patient data was retrospectively analyzed and a literature review performed. RESULTS: We present a unique case of split liver transplantation into two pediatric recipients in which one recipient developed rapidly progressive graft failure approximately 1 week postoperatively requiring urgent retransplantation while the other recipient had an unremarkable postoperative course. Upon clinical manifestation of progressive graft failure, the patient was treated with thymoglobulin, rituximab, intravenous immunoglobulin, and plasmapheresis. Despite this, the patient's clinical status continued to decline and she underwent retransplantation 11 days following her initial liver transplant. CONCLUSION: Seventh-Day Syndrome is a rare complication following liver transplantation that is associated with a high risk of morbidity and mortality. Our case adds to the limited literature on 7DS in children and is the first to report a comparative posttransplant clinical course in two recipients who received split grafts from the same donor.

Inhibition of cysteine-serine-rich nuclear protein 1 ameliorates ischemia-reperfusion injury during liver transplantation in an MAPK-dependent manner.

Hepatic ischemia-reperfusion injury (HIRI) is a critical pathophysiological process during liver transplantation (LT). Multiple genes and signal pathways are dysregulated during HIRI. This study aims to identify genes as potential therapeutic targets for ameliorating HIRI. Datasets containing samples from the human donor liver (GSE151648) and mouse HIRI model (GSE117066) were analyzed to determine differentially expressed genes (DEGs). The selected DEGs were confirmed by real-time PCR and western blot in the hepatocyte hypoxia-reoxygenation (HR) model, mouse HIRI model, and human liver samples after transplantation. Genetic inhibition was used to further clarify the underlying mechanism of the gene in vitro and in vivo. Among the DEGs, CSRNP1 was significantly upregulated (|log FC|= 2.08, P < 0.001), and was positively correlated with the MAPK signal pathway (R = 0.67, P < 0.001). CSRNP1 inhibition by siRNA significantly suppressed apoptosis in the AML-12 cell line after HR (mean Annexin+ ratio = 60.62% vs 42.47%, P = 0.0019), but the protective effect was eliminated with an additional MAPK activator. Knocking down CSRNP1 gene expression by intravenous injection of AAV-shRNA markedly reduced liver injury in mouse HIRI model (ALT: AAV-NC vs AAV-shCsrnp1 = 26,673.5 ± 2761.2 vs 3839.7 ± 1432.8, P < 0.001; AST: AAV-NC vs AAV-shCsrnp1 = 8640.5 ± 1450.3 vs 1786.8 ± 518.3, P < 0.001). Liver-targeted delivery of siRNA by nanoparticles effectively inhibited intra-hepatic genetic expression of Csrnp1 and alleviated IRI by reducing tissue inflammation and hepatocyte apoptosis. Furthermore, CSRNP1 inhibition was associated with reduced activation of the MAPK pathway both in vitro and in vivo. In conclusion, our results demonstrated that CSRNP1 could be a potential therapeutic target to ameliorate HIRI in an MAPK-dependent manner.

A 29-mRNA host-response classifier identifies bacterial infections following liver transplantation - a pilot study.

PURPOSE: Infections are common complications in patients following liver transplantation (LTX). The early diagnosis and prognosis of these infections is an unmet medical need even when using routine biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Therefore, new approaches are necessary. METHODS: In a prospective, observational pilot study, we monitored 30 consecutive patients daily between days 0 and 13 following LTX using the 29-mRNA host classifier IMX-BVN-3b that determine the likelihood of bacterial infections and viral infections. True infection status was determined using clinical adjudication. Results were compared to the accuracy of CRP and PCT for patients with and without bacterial infection due to clinical adjudication. RESULTS: Clinical adjudication confirmed bacterial infections in 10 and fungal infections in 2 patients. 20 patients stayed non-infected until day 13 post-LTX. IMX-BVN-3b bacterial scores were increased directly following LTX and decreased until day four in all patients. Bacterial IMX-BVN-3b scores detected bacterial infections in 9 out of 10 patients. PCT concentrations did not differ between patients with or without bacterial, whereas CRP was elevated in all patients with significantly higher levels in patients with bacterial infections. CONCLUSION: The 29-mRNA host classifier IMX-BVN-3b identified bacterial infections in post-LTX patients and did so earlier than routine biomarkers. While our pilot study holds promise future studies will determine whether these classifiers may help to identify post-LTX infections earlier and improve patient management. CLINICAL TRIAL NOTATION: German Clinical Trials Register: DRKS00023236, Registered 07 October 2020, https://drks.de/search/en/trial/DRKS00023236.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

HOPE Mitigates Ischemia-Reperfusion Injury in Ex-Situ Split Grafts: A Comparative Study With Living Donation in Pediatric Liver Transplantation.

Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT). All consecutive HOPE-Split, SCS-Split and LDLT performed between 2018-2023 for pediatric recipients were included. Post-reperfusion syndrome (PRS, drop ≥30% in systolic arterial pressure) and reperfusion biopsies served as early indicators of IRI. We included 47 pediatric recipients (15 HOPE-Split, 17 SCS-Split, and 15 LDLT). In comparison to SCS-Split, HOPE-Split had a significantly shorter cold ischemia time (CIT) (470min vs. 538 min; p =0.02), lower PRS rates (13.3% vs. 47.1%; p = 0.04) and a lower IRI score (3 vs. 4; p = 0.03). The overall IRI score (3 vs. 3; p = 0.28) and PRS (13.3% vs. 13.3%; p = 1) after HOPE-Split were comparable to LDLT, despite a longer CIT (470 min vs. 117 min; p < 0.001). Surgical complications, one-year graft, and recipient survival did not differ among the groups. In conclusion, HOPE-Split mitigates early IRI in pediatric recipients in comparison to SCS-Split, approaching the gold standard of LDLT.

Circulating Trimethylamine-N-Oxide Is Elevated in Liver Transplant Recipients.

Liver transplant recipients (LTRs) have lower long-term survival rates compared with the general population. This underscores the necessity for developing biomarkers to assess post-transplantation mortality. Here we compared plasma trimethylamine-N-oxide (TMAO) levels with those in the general population, investigated its determinants, and interrogated its association with all-cause mortality in stable LTRs. Plasma TMAO was measured in 367 stable LTRs from the TransplantLines cohort (NCT03272841) and in 4837 participants from the population-based PREVEND cohort. TMAO levels were 35% higher in LTRs compared with PREVEND participants (4.3 vs. 3.2 µmol/L, p < 0.001). Specifically, TMAO was elevated in LTRs with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and polycystic liver disease as underlying etiology (p < 0.001 for each). Among LTRs, TMAO levels were independently associated with eGFR (std. ß = -0.43, p < 0.001) and iron supplementation (std. ß = 0.13, p = 0.008), and were associated with mortality (29 deaths during 8.6 years follow-up; log-rank test p = 0.017; hazard ratio of highest vs. lowest tertile 4.14, p = 0.007). In conclusion, plasma TMAO is likely elevated in stable LTRs, with impaired eGFR and iron supplementation as potential contributory factors. Our preliminary findings raise the possibility that plasma TMAO could contribute to increased mortality risk in such patients, but this need to be validated through a series of rigorous and methodical studies.

Comparison of prophylaxis and preemptive strategy as cytomegalovirus prevention in liver transplant recipients.

OBJECTIVES: Prophylaxis (P) or pre-emptive strategy (PS) in high-risk liver transplant recipients (LTRs) are either recommended. We compared the results of each strategy. METHODS: Two groups of LTR transplanted during two consecutive periods were compared. Only cytomegalovirus (CMV)-mismatched LTR (Donor +/ Recipient -) were included. The primary endpoints were: the onset of polymerase chain reaction-based DNAemia and the proportion of patients with CMV disease. A number of episodes of CMV infection, antiviral therapy, ganciclovir resistance, infectious or immunological complications, cost of both strategies, and survival (1, 5, and 10 years) were also compared. RESULTS: Forty-eight and 60 patients were respectively included in the P and PS groups. Eighteen (38%) in the P group and 56 (93%) in the PS group had CMV DNAemia (p <.0001) with a similar CMV disease rate (16.7% and 15%). Duration of curative therapy was longer in the PS group: 91 days versus 16 (p <.0001). Acute rejection was less frequent (p = .04) and more patients experienced a ganciclovir-resistant CMV infection in the PS group (10% vs. 0, p = .03). The drug-associated cost of PS was higher (10 004 vs. 4804€) and the median number of rehospitalization days tended to be higher (6 vs. 4, p = .06). Survival at any time was similar. CONCLUSION: We reported more CMV DNAemias and ganciclovir-resistant CMV events with PS. The cost of the PS strategy was higher.