Clinical Research Directory

Prediction Models for LDLT Outcomes

Rationale: Living donor liver transplantation (LDLT) has emerged as an important option for patients with end-stage liver disease. To facilitate international and meaningful comparisons, our institution participates in the International LDLT Registry. Several models to predict outcomes post-LDLT have been developed to council and justify the major surgery that the living liver donors undergo. However, most proposed models are at high risk of bias and demonstrate suboptimal discriminative ability. This study aims to externally validate the most promising prediction models and subsequently, develop a new, clinically applicable prediction model for LDLT outcomes, using the International LDLT Registry. Objective(s): The main objective of this study is to develop a new, clinically applicable prediction model for LDLT outcomes, using the International LDLT Registry. The secondary objective is to externally validate the most promising existing prediction models for LDLT outcomes, using the International LDLT Registry. Study type: This is an observational, multicenter cohort study using prospectively collected data from the International LDLT Registry. Registry data will be analyzed retrospectively for the purposes of external model validation and prediction model development. Study population: The study population consists of living liver donors and their corresponding recipients recorded in the International LDLT registry. Methods: For external validation, parameters will be entered in the existing prediction models resulting in the predicted risks. Model discrimination will be measured using the area under the curve (AUC) and by the discrimination slope. The DeLong test will be used to test for difference between the AUC of the different prediction models. Calibration will be evaluated by comparing the observed with the predicted rate of events and graphically represented by calibration plots. For the development of a new prediction model, the outcome of interest is early graft failure, defined as graft loss within 90 days after transplantation. A multivariable logistic regression model will be developed to estimate the individual risk of early graft failure. Internal validation will be performed using bootstrapping, and model performance will be assessed in terms of discrimination and calibration. Model performance will also be tested in subgroups.

The Regenerative Capacity of the Donor Liver After Living Donor Liver Transplantation: an Ambidirectional Cohort Study

Rationale: Living donor liver transplantation (LDLT) offers a promising solution to the organ shortage. During living liver donation, a substantial portion of the donor's liver is resected. Fortunately, the liver has a remarkable capacity to regenerate. However, liver regeneration varies among individuals. Previous studies have identified several clinical factors as potential predictors of regenerative capacity. Nevertheless, these studies are outdated and do not reflect current clinical practice or recent advancements. This study aims to investigate the regenerative capacity of the donor liver following LDLT and identify its clinical predictors. It is hypothesized that the liver regenerates to the original size. Objectives: The main objective of this study is to evaluate the regenerative capacity of the donor liver following LDLT. The secondary objective is to identify clinical predictors of the regenerative capacity of the donor liver following LDLT. Study type: This is an ambidirectional, single-center cohort study using medical records. Study population: The population consists of adult living liver donors aged 18-60 years at the Erasmus MC who donate(d) between May 2004 and June 2026 and gave written informed consent. Methods: General, graft weight and liver volumetry data will be extracted from HiX. The study coordinator will register his findings and analyze them. The paired samples t-test will be used to test for differences in mean remnant liver volume and liver volume 12 months post-donation. In addition, subgroup analyses will be performed for sex, age, weight, type of liver graft donation, anatomical variants, liver steatosis, and donor complications. Multiple linear regression analysis will be performed for sex, age, BMI, donor length of stay, remnant liver volume and percentage, and type of liver graft donation.

Steatosis Assessment Pre-LDLT

There is a major shortage of donor livers in the Netherlands. Living donor liver transplantation (LDLT) is a good solution to this shortage. Donor screening is extensive to minimalize risks for donors and recipients. During screening, the vascular anatomy of the liver is assessed with CT, the bile duct anatomy with MRCP, and liver steatosis with a biopsy. Biopsy is an invasive intervention with some risk of complications. MRCP can aid in steatosis assessment. Previous research suggested that biopsy can be performed on indication. However, the sensitivity of detecting different steatosis percentages on MRCP varies widely, which makes determining the degree of steatosis difficult and less reliable. This project investigates whether MRCP is equally adequate as biopsy in assessing liver steatosis. It may lead to a faster, less burdensome and minimal invasive screening process.

Study on the Clinical Outcomes of ABO-Incompatible Living Donor Liver Transplantation

Evaluate the postoperative survival rate and incidence of rejection in patients undergoing ABO-incompatible living donor liver transplantation; analyze the occurrence of secondary endpoint events such as postoperative vascular complications and biliary complications; and explore relevant risk factors affecting prognosis.

Delayed Infusion of DCreg in Living Donor Liver Transplantation

Phase I/II, single center, prospective, open-label, non-controlled, non-randomized, interventional, cohort study in which low risk living donor liver transplant (LDLT) recipients who are between 1 and 3 years after transplantation and meet specific criteria (no positive crossmatch, no clinically treated rejection within 2 years preceding enrollment, permissive liver function tests (LFTs) within 30 days preceding enrollment, no prior liver biopsy showing significant fibrosis or ductopenia\*) will be enrolled and will undergo a protocol liver biopsy unless they have had a permissive liver biopsy\*\* within 90 days of anticipated immunosuppression weaning. Those patients with permissive liver biopsy\*\* will then receive a single infusion of donor-derived DCreg and will remain on their current standard of care (SOC) immunosuppression. One week after DCreg infusion, immunosuppression weaning will be initiated. Recipients will be slowly weaned off immunosuppression. Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression. They will undergo a liver biopsy at 1 yr and 3 yrs after immunosuppression withdrawal. Participants who are removed from the study protocol at any time will return to standard of care but will continue to be followed by the study team and will undergo a liver biopsy at the end of the study. \* Permissive LFTs are defined as ALT, AST and total bilirubin \< 2.5 times the upper limit of normal. \*\*A permissive biopsy is based on 2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology (the criteria detailed in Table 8, Demetris et al. 2016).

The Correlation Between CT and MRCP Before Living Liver Donation for Liver Blood Vessel Assessment: an Ambidirectional Cohort Study

Living donor liver transplantation (LDLT) is a good solution to the donor liver shortage in the Netherlands. In cases of severe liver disease, LDLT has substantial survival benefits, fewer (future) complications, and an improved quality of life. Donor screening is extensive to minimize risks for both donors and recipients. The liver's blood vessels are assessed using CT and the bile ducts with MRCP. Blood vessel assessment can also be performed using MRCP, which would make the CT unnecessary. Before CT can be removed from the screening procedure, the correlation between blood vessel assessment on CT and MRCP must be clarified. It is hypothesized that CT is equally adequate in assessing liver blood vessels to MRCP.

Biliary Complication Rates in Living Donor Liver Transplantation: a Retrospective Comparative Study of Stent Versus Non-Stent Groups

Despite technological advancements in living donor liver transplantation (LDLT), biliary complications (BC), including biliary anastomotic stricture (BAS) and bile leak (BL), remain unresolved issues that significantly affect patient outcomes. Biliary stenting has emerged as a potential method for reducing BC in LDLT procedures; however, their necessity remains debated. This study aimed to assess the necessity of biliary stenting by retrospectively comparing the bile duct complication rates in LDLT using duct-to-duct anastomosis with or without biliary stenting.

Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma

This study is supposed to make liver transplantation available for treatment in well selected patients suffering from non-resectable intrahepatic cholangiocarcinoma. Donor organ shortage is currently the main problem for organ transplantation world-wide. Thus, the particular indication "non-resectable intrahepatic cholangiocarcinoma" is currently excluded in terms of transplantation. Given those circumstances, transplantation via living donation might be the best option. This procedure does not reduce the deceased donor organ supply because living donation is the primary treatment option in these patients (not subsidiary).