Donor Liver Research Articles

Outcomes following use of hepatitis B surface antigen positive liver allografts in hepatitis B surface antigen negative recipients

The use of positive hepatitis B surface antigen (HBsAg+) liver allografts has been increasing globally and is gaining wider acceptance within the United States. However, most of the data supporting the use of HBsAg+ organs has been in the setting of recipients with chronic hepatitis B. We aim to describe our institutional experience using HBsAg+ liver donors in HBsAg-negative recipients via case series. Between 2019 and 2021, 10 HBsAg-negative recipients received a HBsAg+ liver transplant. Kaplan-Meier survival analysis showed no difference in survival when compared to all other liver transplants performed at the institution during the same period (p=0.5, HR=1.6, CI=0.4-6.5). Based on these findings, the use of HBsAg+ liver donors appears to be safe; however, continued follow-up is required to understand further risks associated with the use of HBsAg+ liver allografts.

Two cases of living donor liver transplantation for colorectal liver metastases in Korea

Two cases of living donor liver transplantation for colorectal liver metastases in Korea

Outcomes of living donor liver transplantation in patients with concurrent extrahepatic malignancy

Outcomes of living donor liver transplantation in patients with concurrent extrahepatic malignancy

Bacterial contamination of autologous blood salvaged during deceased donor liver transplantation: a prospective observational study.

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study.Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr ; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022).

A Study on iPSC-Associated Factors in the Generation of Hepatocytes.

Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes. This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation. Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 × 10 cells/cm of seeding density resulting in good morphology and functionality. This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.

Internal hernia following laparoendoscopic single site surgery: a case report

Laparoscopic donor nephrectomy was introduced in 1995 as a means of minimally invasive surgeries that entail kidney extraction from healthy individuals. Since then, it has widely overtaken the traditional open surgical approaches, especially in live donor nephrectomy procedures worldwide. Laparoendoscopic single-site surgery is considered a more optimized surgical approach utilizing a single incision instead of four. Various studies have scrutinized many of the risk factors related to such surgeries, most commonly: vascular problems, intraoperative organ injury, and postoperative ileus. Other rare complications have not been thoroughly explored due to their decreased prevalence. Internal hernias are considered a rare complication of laparoendoscopic single-site surgery with dangerous repercussions ranging from bowel obstruction to ischemia, and necrosis. Our study presents a rare case of a trans-mesenteric internal hernia following laparoendoscopic single-site surgery. The patient was relatively healthy with no serious medical conditions. However, the past medical history did record a diagnosis of irritable bowel syndrome a few years back. Knowing that the occurrence of internal hernias is infrequent, we recommend that mesenteric defects be taken seriously to avoid the risk of internal hernias and their complications.

Neoadjuvant Pemigatinib as a Bridge to Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma with FGFR2 Rearrangement

Neoadjuvant Pemigatinib as a Bridge to Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma with FGFR2 Rearrangement

Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances

Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers for orthotopic liver transplantation are of great shortage. However, HTx has been confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment and repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs with unique advantages. Small molecules are promising chemical tools to modulate cell fate and function for generating high quality hepatocyte sources. In addition, endothelial barrier, immune responses, and low proliferative efficiency of donor hepatocytes mainly contributes to low cell engraftment and repopulation rate. Interfering these biological processes with small molecules is beneficial for improving cell engraftment and repopulation. In this review, we will discuss the applications and advances of small molecules in modulating cell differentiation and reprogramming for hepatocyte resources and in improving cell engraftment and repopulation as well as its underlying mechanisms.

Splenectomy Before Recipient Hepatectomy for Inflow Modulation Using a Very Small Modified Right Hemiliver Graft: A Case Report

Portal inflow modulation has become standard practice in many transplant centers performing living donor liver transplantation. This is believed to counteract the deleterious effects of excess portal flow into a small-for-size graft. A splenectomy negates the contribution of the splenic vein flow completely and thereby substantially reduces portal inflow. Although it has been adopted as a standard strategy by many Japanese centers for inflow modulation, especially while using left hemiliver grafts, there is justifiable apprehension about its usage due to potential increases in morbidity. Described here is a splenectomy performed while using a modified right hemiliver graft with a graft to recipient weight ratio of 0.49. The challenges in decision making and reasons regarding how such a small graft might have worked without manifestations of small-for-size/flow syndrome are discussed.

The small-for-size syndrome in living donor liver transplantation: current management.

Small-for-size syndrome poses a significant challenge in living donor liver transplantation, with potentially severe consequences including liver failure and death. This review explores the management strategies for SFSS, starting from the pathophysiology of the disease. SFSS arises from insufficient liver mass in the graft and hyperdynamic circulation in cirrhotic recipients, leading to portal hyperperfusion and subsequent liver injury. Risk factors include graft size, quality, recipient factors, and hemodynamic changes during transplantation.Hemodynamic monitoring is crucial during living donor liver transplantation to optimize portal vein and hepatic artery flow. Prevention strategies focus on donor-recipient matching and intraoperative graft inflow modulation. Optimizing venous outflow and avoiding portal hyperperfusion is essential. Management of established small-for-size syndrome involves supportive care, pharmacologic interventions, and radiological and surgical options. Pharmacotherapy includes somatostatin analogues, beta-blockers, and vasopressin analogues to reduce portal flow and pressure. Surgical interventions aim to modulate portal flow and mitigate complications. Retransplantation may be necessary in severe cases, guided by persistent graft dysfunction despite liver flow modulations. In conclusion, preventing and managing small-for-size syndrome in living donor liver transplantation requires comprehensive assessment and tailored interventions. Advancements in graft/recipient matching, hemodynamic monitoring, pharmacologic and surgical techniques aiming to inflow modulation have improved outcomes, enabling successful transplantation even with ultra-small grafts.

Therapeutic Role of Bone Marrow Mesenchymal Stem Cells (BMSCs) in Nonalcoholic Steatohepatitis (NASH) Cirrhosis

Abstract: NASH cirrhosis is a late-stage nonalcoholic fatty liver disease (NAFLD) characterized by high morbidity, high relapse rate, and high mortality, which is clinical to treat. Presently, liver transplantation is the most effective radical treatment, but it is difficult to be widely carried out due to the problems of large surgical trauma, lack of liver donors, and strong immunological rejection. Bone marrow mesenchymal stem cells (BMSCs) are a type of stem cell with characteristics of self-replication, multidirectional differentiation, and easy accessibility. The use of BMSCs for cell transplantation therapy has the advantages of fewer complications and significant efficacy, and it has become an important option for cell transplantation therapy, especially for liver diseases. In this paper, we will review the studies related to the use of BMSCs for the treatment of NASH cirrhosis in recent years.

Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft.

This study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation. Static cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion. This study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels. FMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5ng/mL, n=40) and high-FMN groups (≥37.5ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017). The FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.

A reproducible extended ex-vivo normothermic machine liver perfusion protocol utilising improved nutrition and targeted vascular flows

BackgroundNormothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements. We set out to develop a reproducible protocol for the extended normothermic machine perfusion of whole human livers.MethodsHuman livers declined for transplantation were perfused using a blood-based perfusate at 36 °C using the Liver Assist device (XVIVO, Sweden), with continuous veno-venous haemofiltration in-parallel. We developed the protocol in a stepwise fashion.ResultsPerfusion techniques utilised included: targeted physiological vascular flows, phosphate replacement (to prevent hypophosphataemia), N-acetylcysteine (to prevent methaemoglobin accumulation), and the utilisation of sodium lactate as both a nutritional source and real-time measure of hepatocyte function. All five human livers perfused with the developed protocol showed preserved function with a median perfusion time of 168 h (range 120–184 h), with preserved viability throughout.ConclusionsLivers can be reproducibly perfused in excess of 120 (range 121–184) hours with evidence of preserved hepatocyte and cholangiocyte function.

Letter to the editor: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donors.

Letter to the editor: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donors.

Propensity Score-matched Donor and Recipient Outcomes: Robotic Versus Laparoscopic Donor Right Hepatectomy.

Few studies have examined the long-term outcomes of recipients in minimally invasive donor hepatectomies, particularly comparing robotic and laparoscopic donor procedures. Understanding these outcomes is crucial for optimizing surgical approaches and improving the overall success of living donor liver transplantation. This study aimed to compare the feasibility and safety of robotic donor right hepatectomy (RDRH) and laparoscopic donor right hepatectomy (LDRH) by evaluating total follow-up patient outcomes. This retrospective, single-center study included 117 and 118 donors who underwent RDRH and LDRH between March 2016 and June 2023, respectively. After performing 1:1 propensity score matching, 71 donor-recipient pairs were included in each group. Donor and recipient complications were divided into early (within 90 d) and late (after 90 d) biliary and vascular complications. In the matched cohort, major complication rates of donors were similar in both groups. Bile duct (BD) variation was not significantly different; however, the rates of multiple BD openings (26.8% versus 54.9%; P = 0.001) and major biliary complications in recipients were higher in the LDRH group (22.5% versus 42.3%; P = 0.012). The cumulative biliary complication rate was significantly higher in the LDRH group. Early biliary complications were not significantly different; however, the rate of late biliary complications was higher in the LDRH group (11.3 versus 23.9%; P = 0.047). RDRH demonstrated comparable postoperative complications to LDRH in donors but showed fewer recipient biliary complications. This could be attributed to the precision of robotic dissection and BD division, resulting in fewer multiple BD openings.

Optimization and Protection of Kidney Health in Liver Transplant Recipients: Intra- and Postoperative Approaches.

Postoperative acute kidney injury after liver transplant (LT) has long-term implications for kidney health. LT recipients are at risk of acute kidney injury due to a number of factors related to the donor liver, intraoperative factors including surgical technique, as well as recipient factors, such as pre-LT kidney function and postoperative complications. This review discusses these factors in detail and their impact on posttransplant kidney function. Long-term risk factors such as calcineurin inhibitors have also been discussed. Additionally, the impact of liver allocation policies on pre- and post-LT kidney health is discussed.

Reply: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donor.

Reply: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donor.

Expanding Opportunities for Living Donation: Recommendations From the 2023 Santander Summit to Ensure Donor Protections, Informed Decision Making, and Equitable Access

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Evaluating the Effectiveness of a Large Language Model in the Psychological Assessment of Potential Liver Transplant Candidates: A Feasibility Study

Introduction: The use of artificial intelligence (AI) in medical settings has shown promise in various domains including diagnostics, treatment recommendation, and patient management. Recent advances have explored the potential of AI in pre-surgical assessments, but its application in transplant psychology remains unexplored. The objective of this study is to assess the effectiveness of AI in the context of screening potential liver transplant donors and recipients. To assess the feasibility of using ChatGPT-4 to screen potential liver transplant donors and recipients. Methods: This study utilizes a cross-sectional research design to evaluate the feasibility of using ChatGPT-4 in the preliminary screening of living liver donors and liver transplant candidates. The study aims to determine the accuracy and reliability of ChatGPT-4 in assessing hypothetical scenarios involving potential donors and recipients. Results: The analysis showed no found no significant differences between ChatGPT-4 and the expert panel in assessing liver transplant candidates, demonstrating an overall accuracy of 83.58%, sensitivity of 56.10%, and specificity of 80.49%. Additionally, the Cohen’s Kappa statistic of 0.68 (95% CI: 0.52-0.83) indicated substantial agreement between ChatGPT-4 and the psychologists’ evaluations. The absence of false positives (0%) and a low false negative rate (8%) emphasize ChatGPT-4's cautious and accurate decision-making capabilities. Conclusion: The findings of this study demonstrate that ChatGPT-4 has the potential to serve as an effective screening tool for liver transplant candidates, complementing the work of human experts and enhancing the overall efficiency of the transplant process. While challenges remain, the integration of AI into the liver transplantation workflow could lead to significant improvements in candidate evaluation and patient outcomes, paving the way for the broader application of AI in clinical practice.

Expression of sPD-L1 levels in an ex vivo liver perfusion model.

The programmed cell death protein 1 (PD-1) acts as a central inhibitory immune checkpoint receptor. The soluble form of its primary ligand, sPD-L1, was found to be elevated in serum of patients with cancer, infectious diseases and chronic inflammation. So far, the hepatic origin of sPD-L1 has received relatively little attention and is therefore subject of this study in the context of normothermic machine perfusion (NMP) of liver grafts. sPD-L1 concentrations as well as several well-established clinically relevant laboratory parameters were determined in the perfusate of 16 donor liver grafts undergoing normothermic machine perfusion (NMP) up to 30 hours (h). sPD-L1 levels continuously increased during NMP and significantly correlated with markers of hepatic synthesis (cholinesterase), acute-phase proteins (von Willebrand factor, procalcitonin, antithrombin, interleukin-6, fibrinogen) and liver decay markers (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase). Perfusate leukocytes were in the lower reference range, and decreased after 12h. Mean sPD-L1 levels in the perfusate correlated with donor levels of gamma-glutamyltransferase, alanine aminotransferase, creatinine and blood urea nitrogen. Our study reveals a significant increase of concentration of sPD-L1 following ischemia-reperfusion injury in a hepatic ex vivo model. sPD-L1 concentrations during NMP correlate with established acute-phase proteins and liver cell decay markers suggesting that hepatic sPD-L1 synthesis or shedding increases during the acute phase and cell decay. Furthermore, sPD-L1 correlates with established liver function and synthesis parameters as well as with donor laboratory values and might therefore be a potential biomarker for hepatic function of liver grafts.