Donor Liver Research Articles

Nutritional status and outcomes of the recepients with deceased donor liver transplantation (DDLT) in limited resources

Nutritional status and outcomes of the recepients with deceased donor liver transplantation (DDLT) in limited resources

Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells

Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69+ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions.

S1628 Efficacy of Endoscopic Treatment of Post Living Donor Liver Transplant Biliary Strictures

S1628 Efficacy of Endoscopic Treatment of Post Living Donor Liver Transplant Biliary Strictures

Multiple Swaps Tested: Rehearsal for Triple and Five Liver Paired Exchanges

Despite several advances in living donor liver transplant (LDLT), many potential living liver donors cannot donate their organs to their relatives because of blood group incompatibility and unsuitable anatomy. Liver paired exchange (LPE) can be used to overcome incompatibilities between living donor-recipient pairs. In this study, we report the early and late results of three and five LDLTs performed simultaneously to initiate the more complex LPE program. By demonstrating that our center is capable of performing up to five LDLTs, we have taken an essential step for establishing a complex LPE program.

Development and validation of a model for early survival prediction following liver transplantation based on donor and recipient characteristics

Background Circulating cytokine levels not only correlate with the progression of liver disease but also serve as indicators for the infection status of the body. Growing evidence points to the connection between donor cytokines and graft function following transplantation. This study set out to explore the clinical significance of donor cytokines in predicting liver transplantation prognosis. Methods Data from 172 deceased donor liver transplantations conducted between 2017 and 2022, with available donor serum cytokine information, were collected. The subjects were randomly divided into estimation (n = 120) and validation (n = 52) groups to establish and validate the model. The newly developed SA10 score was compared against established models EAD, MEAF, L-GrAFT7, and L-GrAFT10. Results Donor IL-10, along with donor age and recipient AST peak value within the first 7 days post-operation, was identified as an independent factor associated with recipient survival and was incorporated into the SA10 score. SA10 exhibited robust predictive capability, particularly for 1-month survival (AUC = 0.90, 95% CI = 0.84–0.96), outperforming EAD (AUC = 0.75, 95% CI = 0.60–0.90, p = 0.04) and L-GrAFT7 (AUC = 0.65, 95% CI = 0.49–0.81, p < 0.01). Comparable performance was observed between SA10, MEAF, and L-GrAFT10. Conclusion Donor IL-10 independently influences recipient survival, with the SA10 score demonstrating comparable and even superior predictive ability compared to existing models.

Sublingual Administration of Tacrolimus is Safe and Provides Similar Drug Exposure to Per-oral Route in Liver Transplant Recipients During Early Postoperative Period–A Large, Retrospective, Observational Study

BackgroundPer-oral(PO) administration of Tacrolimus(TAC) results in inadequate trough levels in early post-operative period in liver-transplant(LT) recipients who undergo Roux-en-Y hepaticojejunostomy for biliary reconstruction. Sublingual administration(SL) of tacrolimus provides an alternative route in such patients. ObjectiveTo assess feasibility and safety of SL tacrolimus in adult LT-recipients in early post-operative period and to compare therapeutic efficacy of SL administration of tacrolimus vs.PO route. Patients and MethodSingle-centre, retrospective, observational study carried out in adult living donor liver transplant(LDLT) recipients between January 2022 till December 2022. Recipients who underwent Roux-en-Y hepaticojejunostomy for biliary reconstruction, received tacrolimus through SL route till post-operative day(POD)5 as they were kept nil per oral constituted the study group while recipients who underwent duct-to-duct(D-D) anastomosis for biliary reconstruction were allowed orally from POD1 and received PO-tacrolimus were chosen as controls. Feasibility and safety of SL-Tacrolimus was assessed in terms of patient acceptance, need to discontinue SL-Tacrolimus, incidence of local adverse effects and systemic adverse events like neurotoxicity and nephrotoxicity. Therapeutic efficacy was evaluated by comparing median trough levels(TAC level) achieved and incidence of graft rejection between two groups. Results212 patients underwent LT during the study period of which 125 were included(58 in SL-group and 67 in PO-group). Both groups had comparable baseline characteristics. In SL-group, all patients tolerated SL-Tacrolimus well and no local adverse events were observed. Patients with SL-Tacrolimus administration achieved higher median TAC level(ng/ml) vs.PO route(5.85 vs 5(p=0.06)) despite similar median cumulative tacrolimus dose before assessing TAC-level. 50% patients achieved TAC level ≥6ng/ml in SL-group vs. 35.8% in PO-group(p=0.14). Incidence of neurotoxicity, nephrotoxicity and graft rejection during hospital stay were similar in both the groups(p=0.56,0.82 and 0.28 respectively). ConclusionSL-tacrolimus is safe and provides similar trough levels to PO-tacrolimus and may be considered as viable alternative whenever inadequate TAC-levels are anticipated through per-oral route.

258 - Experience of Brilliant Hospital in performing Liver Donor Magnetic Resonance Cholangiopancreatography (MRCP) for patients undergoing living donor liver transplantation (LDLT)

258 - Experience of Brilliant Hospital in performing Liver Donor Magnetic Resonance Cholangiopancreatography (MRCP) for patients undergoing living donor liver transplantation (LDLT)

Hip Arthroplasty in an Acute-On-Chronic Liver Failure Patient Followed by Early Live Donor Liver Transplant

Abstract An acute-on-chronic liver disease patient, during workup for liver transplant, presented with a transcervical neck of femur fracture following a trivial trauma. High risks were associated with performing the surgery under general anesthesia, coagulation failure, and risks of infection, resulting in intraoperative or post-operative mortality. Addressing each of these risk factors, the patient underwent a cemented bipolar hemiarthroplasty under regional nerve block, followed by early live donor liver transplantation with an uneventful post-op recovery and currently mobilizing without support. In the case of patients with acute-on-chronic liver failure, identifying the risk factors and complications that are expected perioperatively and intraoperatively and further planning the management by a multidisciplinary team approach can result in improved outcomes.

Living donor liver transplantation for hepatocellular carcinoma using expanded criteria and alpha-fetoprotein threshold of 1000 ng/mL

BackgroundNew guidelines propose a minimum 5-year survival of 60% for hepatocellular carcinoma (HCC) with living donor liver transplantation (LDLT). This study aimed to evaluate the 5- and 10-year survival rates after transplantation for the expanded criteria for HCC. MethodsThis single-center retrospective cohort study included 208 patients who underwent LDLT for the expanded criteria (the largest tumor diameter of ≤10 cm, any tumor number, and alpha-fetoprotein [AFP] level of <1000 ng/mL) and analyzed 5- and 10-year overall survival (OS) and recurrence risk (RR) rates. ResultsWith a median follow-up of 65.1 months (IQR, 19.1–80.2), the 5- and 10-year OS and RR rates were 67.0% and 61.0% and 20.5% and 22.5%, respectively. The largest tumor diameter of >6 cm (hazard ratio [HR], 3.7; 95% CI, 1.7–8.2; P = .001) and AFP level of >400 ng/mL (HR, 4.0; 95% CI, 1.8–9.0; P = .001) were predictors of recurrence. Patients outside the Milan criteria (MC) were grouped into low- and high-risk HCC based on tumor size and AFP level. For low-risk HCC (tumor size of <6 cm, any tumor number, and AFP level of <400 ng/mL), the 5-year RR was comparable to the MC and increased the transplant pool by 35.7% (P > .5). The median number of tumors and the rate of microvascular invasion in the high-risk group, low-risk group, and MC were 2.0 (1.0–3.2), 4.0 (2.0–5.0), and 1.0 (1.0–2.0) (P < .001) and 72.2% (13/18), 44.0% (22/50), and 22.8% (32/140) (P < .001), respectively. ConclusionThe expanded criteria met the benchmark for 5-year survival. LDLT for the low-risk HCC in the expanded criteria was associated with an acceptable RR.

Optimization of surgical evaluation algorithms for living donor liver transplantation

BackgroundLiving donor liver transplantation (LDLT) is an established and endorsed alternative for deceased donor liver transplantation with better recipient outcomes. Nevertheless, while extensive evaluation of potential donors is crucial, evaluation algorithms differ between transplant centres and guidelines. MethodsWe included 317 individuals evaluated for LDLT between 07/2007–07/2022 in a retrospective analysis. The evaluation process was analysed to identify the key reasons for declining 77 potential donors. Additionally, 146 donors that underwent LDLT were analysed regarding risk factors for complications. ResultsThe main reasons for donor refusal were liver volumetry (40.3 %) and metabolic factors including obesity or steatotic liver disease (20.8 %). Contrast-enhanced computed tomography (CECT) identified 63.6 % of all declined donors; CECT combined with assessment of medical history, physical examination, blood testing and ultrasonography, identified 87.0 % of declined potential donors. Associated with this selection, complication rates in donors were low (≥II in 17.1 %; none with ≥IVb). Notably, higher age was a risk factor for developing a complication ≥II after hemi-hepatectomy (p = 0.0373). ConclusionsWe propose a progressive 4-step evaluation algorithm that begins with a very basic assessment combined with up-front CECT. This early phase of testing is expected to identify nearly 90 % of ineligible donors, thereby conserving critical resources, time and money, as well as minimising burden for potential donors. FundingJ.M.W. received funding by grant We-4675/6–1 from the Deutsche Forschungsgemeinschaft (DFG) in Bonn, Germany.

Social Network Interventions to Reduce Racial/Ethnic Living Donor Kidney Transplants (LDKT) Disparities: Preliminary Results from the Friends and Family of Kidney Transplant Patients Study

Social Network Interventions to Reduce Racial/Ethnic Living Donor Kidney Transplants (LDKT) Disparities: Preliminary Results from the Friends and Family of Kidney Transplant Patients Study

Specifics and results of liver transplantation in elderly patients

Aim. To determine specific features, frequency, and structure of complications, immediate and long-term results of liver transplantation in elderly patients.Materials and methods. Data on 529 liver transplantations performed consecutively in one medical center from 2010 to 2023 were analyzed. In 386 (73%) cases, the right lobe of the liver of related donors was used for transplantation. At the time of surgery, the patient age ranged from 18 years to 71 years, with 57 (11%) patients being over 60 years old, 215 (40%) patients aged 44–59 years, and 257 (49%) patients aged 18–44 years.Results. Prior to operation, elderly patients were statistically significantly more often diagnosed with arterial hypertension (n = 19; 33%), diabetes mellitus (n = 12; 21%), and on average a reduced glomerular filtration rate (82 ml/min/1.73m2 ). The most frequent indication for transplantation in this group was hepatocellular carcinoma in the setting of cirrhosis (n = 19; 33%). No statistically significant differences in other preoperative characteristics, parameters of donors and operations, peculiarities of the course of the early postoperative period, frequency, structure of complications and lethal outcomes were found. The one-, five-, and ten-year survival rates for recipients over 60 years old were 82%, 72%, and 36%; for recipients aged 44–59 years old – 88%, 79%, and 70%; and for recipients aged 18–44 years old – 86%, 80%, and 74%, respectively.Conclusion. In the studied cohort, older age was not associated with excessive risks of complications and early postoperative mortality. Given the higher prevalence of comorbidities in this group, preoperative examination should be aimed at, among other things, diagnostics of possible (hidden) cardiovascular and oncologic diseases. The development and introduction of new cardio-, nephro-, and oncoprotective regimens of immunosuppressive therapy seems to be an important measure not only for the surgical treatment of elderly patients, but also for recipients living with a transplanted liver for a long time.

Exploring Anesthesiology Management of Living Donor Liver Transplantation: Survey From the Society for the Advancement of Transplant Anesthesia and the Korean Society for Transplantation Anesthesiologists.

While living donor liver transplantation (LDLT) serves as the predominant method of adult liver transplant (LT) in the Republic of Korea (ROK), it represents a minority of LT in the United States (US). A survey was conducted to gain insight into these nations' anesthetic management. An electronic questionnaire was distributed to directors of LT anesthesiology overseeing LDLT programs in both countries between May 2021 and October 2021. The response rate was 93.0% (100% [37/37] in the US and 80% [16/20] in the ROK). Both countries mainly adhered to deceased donor LT recipient management practices, including the frequency of routine pulmonary artery catheter use, transesophageal echocardiography, and point-of-care coagulation monitoring. Differences were observed in early extubation of recipients (US vs. ROK: 39.7%vs. 14.7% of all cases), participation in donor selection meetings (88.9% [32/36] vs. 6.3% [1/16], p < 0.0001), application of the Enhanced Recovery After Surgery donor protocol (69.4% [25/36] vs. 12.5% [2/16], p < 0.0001), and cell saver usage for donors (94.4% [34/36] vs. 18.8% [3/16], p < 0.0001). More ROK programs implemented simultaneous donor/recipient anesthesia supervision by a single anesthesiologist. Several important differences were identified between the US and the ROK in adult LDLT anesthetic management.

Deceased donor liver transplantation for post-hepatectomy liver failure with fixed pupils

Deceased donor liver transplantation for post-hepatectomy liver failure with fixed pupils

Clinical profile and outcome of kidney transplantation at Muhimbili National Hospital, Tanzania

BackgroundKidney transplantation is the definitive treatment option for chronic kidney failure, offering improved quality of life and extended survival. Access to kidney transplantation is limited in the Sub-Saharan Africa (SSA) region, with only a few countries with established services. Tanzania started its program five years ago, for the sustainability of the program it is important to understand the outcome. Therefore, this study was conducted to determine the clinical outcomes and survival rates of kidney transplant recipients at Muhimbili National Hospital in Tanzania, in the absence of a national transplant registry, since the inception of the program.MethodsThis was a retrospective study conducted among kidney transplant recipients from live donors at Muhimbili National Hospital (MNH) between November 2017 and February 2022. Analyses were performed to assess baseline characteristics, post-transplant complications, and patient and graft survival.ResultsIn our study of 68 kidney transplant recipients, the majority of recipients were male (63.2%) with a mean age of 45.8 years and under medical insurance (88.2%). The predominant cause of CKD was hypertension (58.2%) with recipients undergoing dialysis for a mean duration of 14.4 months, and basiliximab being the most commonly used induction medication (57.3%). The majority of donors were males (64.7%) and had first-degree relationships with recipients (76.5%). Haploid HLA mismatch was observed in 36.8% of cases. One-year patient and graft survival rates were 91.2% and 96.7%, respectively, with infection being the primary cause of death (n = 5), and more than half of deceased patients died with a functioning graft (n = 4).ConclusionOur study underscores favorable one-year patient and graft outcomes among kidney transplant recipients at Muhimbili National Hospital, Tanzania. However, challenges persist, notably with infections posing ongoing difficulties for this cohort.

Real-time segmentation of biliary structure in pure laparoscopic donor hepatectomy

Pure laparoscopic donor hepatectomy (PLDH) has become a standard practice for living donor liver transplantation in expert centers. Accurate understanding of biliary structures is crucial during PLDH to minimize the risk of complications. This study aims to develop a deep learning-based segmentation model for real-time identification of biliary structures, assisting surgeons in determining the optimal transection site during PLDH. A single-institution retrospective feasibility analysis was conducted on 30 intraoperative videos of PLDH. All videos were selected for their use of the indocyanine green near-infrared fluorescence technique to identify biliary structure. From the analysis, 10 representative frames were extracted from each video specifically during the bile duct division phase, resulting in 300 frames. These frames underwent pixel-wise annotation to identify biliary structures and the transection site. A segmentation task was then performed using a DeepLabV3+ algorithm, equipped with a ResNet50 encoder, focusing on the bile duct (BD) and anterior wall (AW) for transection. The model’s performance was evaluated using the dice similarity coefficient (DSC). The model predicted biliary structures with a mean DSC of 0.728 ± 0.01 for BD and 0.429 ± 0.06 for AW. Inference was performed at a speed of 15.3 frames per second, demonstrating the feasibility of real-time recognition of anatomical structures during surgery. The deep learning-based semantic segmentation model exhibited promising performance in identifying biliary structures during PLDH. Future studies should focus on validating the clinical utility and generalizability of the model and comparing its efficacy with current gold standard practices to better evaluate its potential clinical applications.

Factors Affecting Intraoperative Blood Transfusion Requirements during Living Donor Liver Transplantation.

Background: Intraoperative blood transfusion (IOBT) during liver transplantation (LT) has negative outcomes, and it has been shown that an increasing number of these procedures may no longer require IOBT. Regarding living donor liver transplantation (LDLT), the literature on the pre-transplant predictors of IOBT is quite heterogeneous and deficient. In this study, we reviewed our experience of IOBT among a homogenous cohort of adult right-lobe LDLTs. Methods: We conducted a retrospective analysis of prospectively collected data on adult LDLT recipients between January 2018 and October 2023. Two groups were constructed (No-IOBT vs. IOBT) for the exploration of pre- and intraoperative predictors of IOBT using univariate and multivariate analyses. An ROC curve analysis was applied to identify possible cut-offs. The one-year post-LDLT overall survival was compared using the Kaplan-Meier method. A p-value < 0.05 was considered statistically significant. Results: A total of 219 adult LDLT recipients were enrolled. The No-IOBT (n = 56) patients were mostly males (p = 0.016), with higher preoperative levels of HGB (p < 0.001), fibrinogen (p = 0.005), and albumin (p = 0.007) and a lower incidence of pre-transplant upper abdominal surgery (p = 0.017), portal vein thrombosis (p = 0.04), hepatorenal syndrome (p = 0.015), and ascites (p = 0.02) than the IOBT group (n = 163). The No-IOBT group had a shorter anhepatic phase (p = 0.002) and received fewer intravenous crystalloids (p = 0.001). In the multivariate analysis, the pre-transplant HGB (p < 0.001), fibrinogen (p < 0.001), and albumin (p = 0.04) levels were independent predictors of IOBT, showing the following cut-offs in the ROC curve analysis: HGB ≤ 11.5 (AUC: 0.800, p < 0.001), fibrinogen ≤ 125 (AUC: 0.638, p = 0.0024), and albumin ≤ 3.6 (AUC: 0.663, p = 0.0002). These were significantly associated with the No-IOBT group. The one-year overall survival of the No-IOBT and IOBT groups was 100% and 83%, respectively (p = 0.007). Conclusions: IOBT during LDLT is associated with inferior outcomes. The increased need of IOBT during LT can be predicted by evaluating serum levels of hemoglobin, albumin and fibrinogen before liver transplantation.

Arterial anastomosis in LDLT: techniques and risks.

Reconstructing the hepatic artery in adult living donor liver transplantation is technically challenging, with complications leading to significant morbidity and mortality. Early arterial thrombosis can result in a mortality rate up to 50%, often necessitating re-transplantation. The most common techniques for arterial anastomosis include end-to-end reconstruction with interrupted or continuous sutures, either using magnifying loupes or a microscope. Although microscopes provide enhanced precision, they do not significantly reduce early thrombosis rates compared to loupes but increase surgical time. Overall, surgeons can achieve early thrombosis rates below 1% with experience and evolving techniques.

Infective endocarditis with metastatic infections in a renal transplant recipient: a case report

BackgroundInfective endocarditis is an uncommon but well-known post-transplant complication with significant morbidity and mortality. It has been observed to be about 171 times more common in solid organ transplant patients than in the general population. With the increasing rate of end-stage kidney disease, the higher demand for kidney transplantation with better graft survival, and life expectancy rates, more transplant recipients may develop infective endocarditis as a late post-transplant complication. Prompt diagnosis of infective endocarditis is therefore necessary to avert graft loss and other life-threatening outcomes.Case presentationWe present a case of a 52-year-old African patient who had a live donor kidney transplant 18 months prior to presentation and had been on oral tacrolimus 5 mg every morning/4.5 mg every evening, mycophenolic acid (MPA) 720 mg twice daily, and oral prednisolone 10 mg daily as maintenance immunosuppressive medications. Regarding the above immunosuppressive medications, he had been in good health and had a functioning transplant graft. He presented with a resolving right thigh swelling, recurrence of fever, new onset left hemiplegia, and seizures. Enterococcus faecalis infective endocarditis was diagnosed with metastatic brain abscesses, which was treated with intravenous vancomycin and gentamycin for 5 weeks. There are very few reported cases of infective endocarditis due to Enterococcus faecalis, and this case is unique because the initial presentation was pyomyositis.ConclusionInfective endocarditis with septic embolization to the brain should be considered in kidney transplant recipients with pyomyositis and multiple rim-enhancing lesions, especially in the late post-transplant period with Enterococcal spp. as an emerging cause of infective endocarditis in kidney transplant recipients. Clinicians will need to have a high index of suspicion to aid early diagnosis with appropriate treatment to prevent adverse outcomes.

Outcomes of Older Primary Kidney Transplant Recipients by Induction Agent and High-risk Viral Discordance Status in the United States.

The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients. We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics. Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival. In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.