0000000000401012
AUTHOR
José Mir
Functional assessment of the quality of human hepatocyte preparations for cell transplantation.
Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. Good quality freshly isolated or cryopreserved human hepatocytes are needed for clinical transplantation. However, isolation, cryopreservation, and thawing processes can seriously impair hepatocyte viability and functionality. The aim of the present study was to develop a fast and sensitive procedure to estimate the quality of hepatocyte preparations prior to clinical cell infusion. To this end, cell viability, attachment efficiency, and metabolic competence (urea synthesis and drug-metabolizing P450 activities) were selected as objective criteria. Viability of hepat…
A score model for the continuous grading of early allograft dysfunction severity
Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons of liver transplant outcomes and management of recipients among and within centers. We sought to develop a model for the quantitative assessment of early allograft function [Model for Early Allograft Function Scoring (MEAF)] after transplantation. A retrospective study including 1026 consecutive liver transplants was performed for MEAF score development. Multivariate data analysis was used to select a small number of postoperative variables that adequately describe EAD. Then, the distribution of these variables was mathematically modeled to assig…
Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction
Background & Aims Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD. Methods A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate g…
Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma
Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden </= 10 cm). Patients with cirrhosis and HCC included on the waiting list (WL) from 1991 to 2006 were retrospectively analyzed. Outcomes in patients who had tumors within and beyond the MC were compared. The survival analysis was done (1) with the intention-to-treat principle and (2) among transplante…
Functional characterization of hepatocytes for cell transplantation: customized cell preparation for each receptor.
The first indication of hepatocyte transplantation is inborn liver-based metabolic disorders. Among these, urea cycle disorders leading to the impairment to detoxify ammonia and Crigler-Najjar Syndrome type I, a deficiency in the hepatic UDP-glucuronosyltransferase 1A1 present the highest incidence. Metabolically qualified human hepatocytes are required for clinical infusion. We proposed fast and sensitive procedures to determine their suitability for transplantation. For this purpose, viability, attachment efficiency, and metabolic functionality (ureogenic capability, cytochrome P450, and phase II activities) are assayed prior to clinical cell infusion to determine the quality of hepatocyt…
Comparison of results of combined liver-kidney transplantation vs. isolated liver transplantation
Introduction. Combined liver-kidney transplantation (LKT) is the best therapeutic option for patients with end-stage liver and kidney disease. Objectives. To analyze baseline characteristics and clinical outcome of LKT compared to isolated liver transplantation (LT). Material and methods. The study included 16 LKT performed between 1998 and 2006 and 32 LT matched by age, sex, date and indication for transplantation. Demographic, pretransplant, post-transplant and survival variables were analyzed. Results. As planned by the study design, mean age, distribution by sex and indication for LT were similar between groups. The most common indication for LT was HCV- and/or alcohol-induced cirrhosis…
Neonatal Livers: A Source for the Isolation of Good-Performing Hepatocytes for Cell Transplantation
Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. However, the supply of hepatocytes is limited given the shortage of organs available to isolate good-functioning quality cells. Neonatal livers may be a potential source alternative to adult livers to obtain good-performing hepatic cells for hepatocyte transplantation, which has not yet been explored profoundly. High-yield preparations of viable hepatocytes were isolated from 1- to 23-day-old liver donors, cryopreserved, and banked. Cell integrity and functional quality assessment were performed after thawing. Neonatal hepatocytes showed better postthawing recovery …
Cirrhosis of mixed etiology (hepatitis C virus and alcohol): Posttransplantation outcome-Comparison with hepatitis C virus-related cirrhosis and alcoholic-related cirrhosis
Hepatitis C virus (HCV)-related liver disease is enhanced by alcohol consumption. Of HCV-related liver transplantation (LT) recipients, 25% have a history of alcohol intake. The purpose of this research was to determine whether LT outcome differs between patients with cirrhosis of mixed etiology compared to HCV or alcohol alone. Of 494 LT (1997-2001), recipient/donor features, post-LT histological, metabolic complications [hypertension, diabetes-diabetes mellitus (DM)], and de novo tumors were compared in 3 groups [HCV-related cirrhosis = 170 (HCV group), alcohol-related cirrhosis (alcohol group) = 107, and cirrhosis of mixed etiology (mixed group) = 60]. Protocol biopsies were done in HCV …