Donor Liver Research Articles

Challenges and strategies in managing severe portopulmonary hypertension during living donor liver transplantation: A clinical case study

Challenges and strategies in managing severe portopulmonary hypertension during living donor liver transplantation: A clinical case study

Dynamics of Ischemia/Reperfusion Injury Markers During Normothermic Liver Machine Perfusion

Background. A comprehensive mechanistic assessment of normothermic machine perfusion (NMP) is an essential step toward identifying biomarkers to assess liver viability. Although some studies have evaluated the effect of NMP on inflammation markers, there are other key pathological mechanisms involved in ischemia/reperfusion injury (IRI) that have not yet been evaluated. Methods. Eight human donor livers preserved by NMP were included to analyze IRI during preservation. Concentrations of several biomarkers involved in different biological processes of IRI were measured in the perfusate. Results. Perfusate levels of intercellular adhesion molecule 1, P-selectin, vascular cell adhesion molecule 1, metalloproteinase with thrombospondin motif type 1, member 13, phospholipase A2 group VII, and syndecan-1 progressively increased during NMP. Noteworthy, perfusate lactate levels showed a strong correlation with C-X-C motif chemokine ligand 10 (P = 0.001), intercellular adhesion molecule 1 (P = 0.01), and urokinase plasminogen activator (P = 0.001). Conclusions. Perfusate lactate correlates with the main underlying biological mechanisms occurring in the NMP environment. Moreover, several IRI biomarkers accumulate during NMP, which may limit the extent of the benefits of this technology.

Use of Intraoperative Doppler Ultrasonography in Predicting Life-Threatening Vascular Complications After Adult Deceased Donor Liver Transplantation

Use of Intraoperative Doppler Ultrasonography in Predicting Life-Threatening Vascular Complications After Adult Deceased Donor Liver Transplantation

Clinicopathological Characteristics of Neutrophil-Rich Hepatocellular Carcinoma: An Uncommon Subtype of Primary Liver Cancer.

Introduction. Neutrophil-rich hepatocellular carcinoma (HCC) is an extremely uncommon subtype of HCC with an overall incidence of <1%. Neutrophil-rich HCC shows poor cellular differentiation and sarcomatoid transformation in most patients. There is prominent neutrophilic inflammatory cell infiltration in the tumor. These tumors are associated with poor prognosis, high rate of recurrence, and metastasis. Methods. Herein, we investigated 4 patients with neutrophil-rich HCC reported at our center. Clinical, radiological, and pathological findings were reviewed. Immunophenotypic characterization of the tumors were done. Granulocyte colony-stimulating factor (G-CSF), programmed cell death ligand 1 (PD-L1), and mismatch repair immunostains were performed in all 4 tumors. Results. We report 4 neutrophil-rich HCCs in 3 male patients and one female patient with an age range of 43 to 64 years. Three underwent living donor liver transplantation and one underwent right hepatectomy. Tumor measured 0.5 cm to 12 cm in maximum dimension. Histologically, tumors demonstrated moderate to marked cellular pleomorphism. Spindle cell transformation was noted in 3 tumors. Three tumors showed vascular invasion, and one tumor showed bile duct invasion. Immunopositivity for Hep Par-1, arginase-1, and glypican-3 was present in all tumors. Tumors also expressed stemness markers including KRT19 and EpCAM. Cytoplasmic positivity for G-CSF and immunoexpression of PD-L1 was demonstrated. We also report proficient mismatch repair by immunohistochemistry in all tumors. Conclusion. Neutrophil-rich HCC is an aggressive primary liver cancer which demonstrates stemness-related features. Programmed cell death ligand 1 expression in tumor cells suggests distinct immunogenic features and potential role of anti-PD-L1 therapies in inoperable disease.

Unlocking the Promise of Liver Perfusion Technologies for Pediatric Transplantation: A State-of-the-Art Review.

Outcomes after pediatric liver transplantation are generally excellent, but the limited avavailability of suitable, size-matched liver allografts remains a significant barrier. Machine perfusion technology has emerged as a promising approach to expand the donor pool, enabling the use of less ideal whole liver grafts, such as livers donated after circulatory death, and enhancing the execution of split liver transplantation. This review examines the application of machine perfusion in pediatric liver transplantation, focusing on two primary techniques: hypothermic oxygentaed perfusion and normothermic machine perfusion. These methods optimize storage, resuscitation, and assessment of liver grafts before transplantation, potentially expanding the range of usable donor organs. The use of machine perfusion allows for the consideration of suboptimal donor livers and facilitates split liver transplantation, both of which could increase organ availability for pediatric patients. Implementation of machine perfusion could also help reduce waiting list mortality by enabling the safe use of a broader spectrum of donor organs. Adoption of machine perfusion in pediatric liver transplantation will require collaborative, multidisciplinary efforts across transplant centers. By fostering cooperative learning and sharing resources. the integration of machine perfusion into clinical practice has the potential to reduce mortality among children awaiting liver transplantation.

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.

Early Outcomes Of Living Donor Liver Transplant Recipients In A University Teaching Hospital Of Nepal

Introduction: The burden of chronic liver disease (CLD) is on the rise and liver transplantation remains the best treatment modality for the end stage liver disease (ESLD). Tribhuvan University Teaching Hospital has started doing living donor liver transplantation (LDLT) and we aim to report our experience and early postoperative outcomes of the first 10 living donor liver transplants performed in our institute. Methods: This is a retrospective review and included all patients who were operated for LDLT from the year 2019 to 2023 for various indications. Demographic data, Model for End-Stage Liver Disease score, Child score, etiology of CLD, liver graft type, graft-to-recipient weight ratio, operative time, blood transfusion and complications were analysed. Results: From 2019 to 2023, in total, 10 patients underwent LDLT, including one paediatric transplant. The most common etiology was alcohol (50%) and right lobe was the preferred graft. The average operative time was 7.9 ± 2.56 hours. There were no re exploration or re transplantation. The mean duration of hospital stay was around 21.37 ± 6.43 days. All patients were followed for one to five years. Four recipients had Clavien Dindo Grade II and above complications, including bile leak and post-operative bleeding. One mortality occurred on 27th post-operative day due to covid infection. Conclusions: Living donor liver transplantation is a feasible option for patients with end stage liver disease and is safe to be performed in low volume centre with the help of expertise and good team work.

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.

First series of Living Donor Liver Retransplants from India: Challenges and Outcomes

BackgroundThere is paucity of Indian data on long term survival after living donor liver transplant (LDLT) or the need for retransplant. In this article, we report the first series of retransplants from India with focus on indications, technical challenges and results. MethodsRetrospective study on 29 patients undergoing a liver retransplant (re-LT) was analysed with respect to survival outcomes and post operative complications. Patients were divided into early and late retransplant groups based on whether re-LT was performed within or beyond 30 days of primary transplant. ResultsLiver retransplant was performed in 29 (0.81%) patients out of a total of 3563 liver transplants ( 28 living donor and 1 deceased donor liver transplant). The primary transplant was a LDLT in 27 (93%) patients. Retransplant was performed at a median of 26 days after the first transplant. Re-LT was performed early (within 30 days) in 17 (59%) patients and late (beyond 30 days) in 12 (41%). Hepatic artery thrombosis (53%) and early graft dysfunction (47%) were the indications for early retransplant while biliary complications (50%) and chronic rejection (33%) were primary indications for late retransplant. Post retransplant complications occurred in 22 (75%) patients, the commonest being gram negative bacterial sepsis.The 30-day mortality following retransplant was 27% (8 of 29). The primary cause of mortality was gram negative septicemia. The mortality in the late retransplant group (2, 16.6%) was lower compared to the early retransplant group (6,35%). ConclusionRe-transplant using living donors is a viable option in properly selected patients with prior LDLT.

Digital single-operator cholangioscopy for difficult anastomotic biliary strictures in living donor liver transplantation recipients after failure of standard ERCP: SPYPASS-2 study

Digital single-operator cholangioscopy for difficult anastomotic biliary strictures in living donor liver transplantation recipients after failure of standard ERCP: SPYPASS-2 study

Management of preoperative recipient portal vein thrombosis in living donor liver transplantation

Management of preoperative recipient portal vein thrombosis in living donor liver transplantation

Small for size syndrome in living donor liver transplantation- Prevention and management

Small for size syndrome in living donor liver transplantation- Prevention and management

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.

Recurrence of HCC after living donor liver transplantation, retrospective cohort study of a single centre experience.

Recurrence of HCC after living donor liver transplantation, retrospective cohort study of a single centre experience.

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.