0000000000088326
AUTHOR
Eugenia Pareja
showing 18 related works from this author
Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.
2001
Abstract Background/Aims : Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. Methods : Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely prese…
Improved in vivo efficacy of clinical-grade cryopreserved human hepatocytes in mice with acute liver failure.
2020
Clinical hepatocyte transplantation short-term efficacy has been demonstrated; however, some major limitations, mainly due to the shortage of organs, the lack of quality of isolated cells and the low cell engraftment after transplantation, should be solved for increasing its efficacy in clinical applications. Cellular stress during isolation causes an unpredictable loss of attachment ability of the cells, which can be aggravated by cryopreservation and thawing. In this work, we focused on the use of a Good Manufacturing Practice (GMP) solution compared with the standard cryopreservation medium, the University of Wisconsin medium, for the purpose of improving the functional quality of cells …
Functional assessment of the quality of human hepatocyte preparations for cell transplantation.
2008
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…
Long-term outcome of ‘long-term liver transplant survivors’
2013
There are few studies focusing on long-term complications in liver transplant (LT) recipients. The aim of this study was to define the outcome of LT recipients having survived at least 10 years from LT. Of 323 adult LT done between 1991 and 1997, the 167(52%) alive >10 years post-LT (baseline time) formed the study population. Long-term outcome measures included the following: immunosuppression, metabolic complications [obesity, arterial hypertension (AH), diabetes, dislypidemia], cardiovascular events (CVE), chronic renal dysfunction-CRD, and de novo tumors. Median age at LT was 50 years. Most common indication was postnecrotic cirrhosis (89%), mostly because of HCV (46%). At study-baselin…
Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.
2012
Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cu…
A score model for the continuous grading of early allograft dysfunction severity
2014
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…
Estimating the Patient-Specific Relative Stiffness Between a Hepatic Lesion and the Liver Parenchyma
2017
This paper presents a novel non-invasive methodology to obtain the patient-specific relative stiffness between a hepatic lesion and the liver parenchyma in vivo. This relative stiffness can be used as a biomarker about the type of lesion. This biomarker together with the rest of pathological information can be used to plan a biopsy, an image-guide intervention or a radiation therapy. This relative stiffness is estimated by means of the finite element simulation of the breathing process, which is embedded in an optimization routine based on genetic algorithms. This routine was aimed at finding the patient-specific relative stiffness between a hepatic lesion and the liver parenchyma for the p…
Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction
2014
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…
Estimation of the elastic parameters of human liver biomechanical models by means of medical images and evolutionary computation.
2013
This paper presents a method to computationally estimate the elastic parameters of two biomechanical models proposed for the human liver. The method is aimed at avoiding the invasive measurement of its mechanical response. The chosen models are a second order Mooney–Rivlin model and an Ogden model. A novel error function, the geometric similarity function (GSF), is formulated using similarity coefficients widely applied in the field of medical imaging (Jaccard coefficient and Hausdorff coefficient). This function is used to compare two 3D images. One of them corresponds to a reference deformation carried out over a finite element (FE) mesh of a human liver from a computer tomography image, …
Towards a Rapid Screening of Liver Grafts at the Operating Room Using Mid-Infrared Spectroscopy
2020
The estimation of steatosis in a liver graft is mandatory prior to liver transplantation, as the risk of graft failure increases with the level of infiltrated fat. However, the assessment of liver steatosis before transplantation is typically based on a qualitative or semiquantitative characterization by visual inspection and palpation and histological analysis. Thus, there is an unmet need for transplantation surgeons to have access to a diagnostic tool enabling an in situ fast classification of grafts prior to extraction. In this study, we have assessed an attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic method compatible with the requirements of an operatio…
Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma
2008
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…
Comparison of results of combined liver-kidney transplantation vs. isolated liver transplantation
2013
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…
A robust reprogramming strategy for generating hepatocyte-like cells usable in pharmaco-toxicological studies.
2023
Abstract Background High-throughput pharmaco-toxicological testing frequently relies on the use of established liver-derived cell lines, such as HepG2 cells. However, these cells often display limited hepatic phenotype and features of neoplastic transformation that may bias the interpretation of the results. Alternate models based on primary cultures or differentiated pluripotent stem cells are costly to handle and difficult to implement in high-throughput screening platforms. Thus, cells without malignant traits, optimal differentiation pattern, producible in large and homogeneous amounts and with patient-specific phenotypes would be desirable. Methods We have designed and implemented a no…
Steatotic liver: a suitable source for the isolation of hepatic progenitor cells.
2011
Background: Alternative and/or complementary sources of cells such as hepatic progenitor cells (HPC) are under investigation for hepatic cell therapy purposes. Steatotic livers are those most commonly rejected for clinical transplantation and are also unsuitable for good quality hepatocyte isolation. Aim: Taken together these two facts, our aim was to investigate whether they could represent a suitable source for the isolation of progenitor cells. Methods: Rats fed for 7 weeks with methionine–choline deficient diets showing proved steatotic signs (i.e. increase in hepatic lipids; macrovesicular steatosis) and steatotic and normal human liver samples were used to study the expression of HPC …
Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity.
2001
CYP activity and protein contents have been measured in human liver using different techniques. In contrast, CYP mRNA data are scarce and the relationships between CYP mRNA contents and activities have not been established. These studies deserve further attention because mRNA determinations by RT-PCR require a very small amount of material (e.g., liver needle biopsy) and could provide important data regarding CYP expression regulation. In this study we measured in 12 human liver samples the mRNA contents of 10 CYPs by quantitative RT-PCR and the metabolic activities using specific substrates. mRNA contents and activities showed high correlation coefficients for CYP1A1, CYP1A2, CYP3A4, CYP2D…
Data set: Towards a rapid screening of liver grafts at the operating room using mid-infrared spectroscopy
2020
The estimation of steatosis in a liver graft is mandatory prior to liver transplantation, as the risk of graft failure increases with the level of infiltrated fat. However, the assessment of liver steatosis before transplantation is typically based on a qualitative or semi-quantitative characterization by visual inspection and palpation, and histological analysis. Thus, there is an unmet need for transplantation surgeons to have access to a diagnostic tool enabling an in situ fast classification of grafts prior extraction. In this study, we have assessed an Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopic method compatible with the requirements of an operation…
Data set: Towards a rapid screening of liver grafts at the operating room using mid-infrared spectroscopy
2020
The estimation of steatosis in a liver graft is mandatory prior to liver transplantation, as the risk of graft failure increases with the level of infiltrated fat. However, the assessment of liver steatosis before transplantation is typically based on a qualitative or semi-quantitative characterization by visual inspection and palpation, and histological analysis. Thus, there is an unmet need for transplantation surgeons to have access to a diagnostic tool enabling an in situ fast classification of grafts prior extraction. In this study, we have assessed an Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopic method compatible with the requirements of an operation…
Data set: Towards a rapid screening of liver grafts at the operating room using mid-infrared spectroscopy
2020
The estimation of steatosis in a liver graft is mandatory prior to liver transplantation, as the risk of graft failure increases with the level of infiltrated fat. However, the assessment of liver steatosis before transplantation is typically based on a qualitative or semi-quantitative characterization by visual inspection and palpation, and histological analysis. Thus, there is an unmet need for transplantation surgeons to have access to a diagnostic tool enabling an in situ fast classification of grafts prior extraction. In this study, we have assessed an Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopic method compatible with the requirements of an operation…