Hepatocyte transplantation program: Lessons learned and future strategies.

This review aims to share the lessons we learned over time during the setting of the hepatocyte transplantation (HT) program at the Hepatic Cell Therapy Unit at Hospital La Fe in Valencia. New sources of liver tissue for hepatocyte isolation have been explored. The hepatocyte isolation and cryopreservation procedures have been optimized and quality criteria for assessment of functionality of hepatocyte preparations and suitability for HT have been established.

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.

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.

[Current status and future perspectives of hepatocyte transplantation].

The imbalance between the number of potential beneficiaries and available organs, originates the search for new therapeutic alternatives, such as Hepatocyte transplantation (HT).Even though this is a treatment option for these patients, the lack of unanimity of criteria regarding indications and technique, different cryopreservation protocols, as well as the different methodology to assess the response to this therapy, highlights the need of a Consensus Conference to standardize criteria and consider future strategies to improve the technique and optimize the results.Our aim is to review and update the current state of hepatocyte transplantation, emphasizing the future research attempting to solve the problems and improve the results of this treatment.

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.

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.

Effect of calcineurin inhibitors in the outcome of liver transplantation in hepatitis C virus-positive recipients.

Background: There is a paucity of good studies evaluating the impact of calcineurin inhibitors on posttransplantation outcome in hepatitis C virus (HCV)-infected liver transplant (LT) recipients.

Methods: We sought to determine whether there are differences on posttransplantation survival and histologic recurrence in HCV-LT recipients based on initial immunosuppression (IS) by conducting a prospective study comparing tacrolimus (Tac) versus cyclosporine-based IS in patients undergoing LT between 2001 and 2007. Protocol liver biopsies were performed.

[Role of resection surgery in breast cancer liver metastases. Experience over the last 10 years in a reference hospital].

Introduction: Breast cancer liver metastases (BCLM) are considered as a systemic disease which is mainly treated with chemotherapy, while the role of surgical resection still remains to be well defined. The aim of the study is to analyse the survival and prognostic factors predictive of mortality in patients with BCLM treated by liver resection.

Material And Methods: A total of 21 patients were operated on between 1998-2008, with liver resection being performed on 12.

[Epithelioid hemangioendothelioma: an uncommon liver tumor].

We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome.

[Hepatic cell transplantation: a new therapy in liver diseases].

Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.

[Indications and results of liver retransplantation: experience with 1181 patients at the University Hospital La Fe].

Unlabelled: Liver retransplantation (LrT) is the only therapeutic option for irreversible failure of a hepatic graft and accounts for 2.9%-24.0% of all liver transplantations (LT).

[Hepatic cell transplantation. Technical and methodological aspects].

Hepatic cell transplantation consists of grafting already differentiated cells such as hepatocytes. Human hepatocytes are viable and functionally active. Liver cell transplantation is carried out by means of a 3-step method: isolation of hepatocytes from donor liver rejected for orthotopic transplantation, preparing a cell suspension for infusion and, finally, hepatocytes are implanted into the recipient.

Comparative prospective study of two liver graft preservation solutions: University of Wisconsin and Celsior.

University of Wisconsin solution (UWS) is the gold standard for graft preservation. Celsior solution (CS) is a new solution not as yet widely used in liver grafts. The aim of this study was to compare the liver function of transplanted grafts stored in these 2 preservation solutions.

Step-by-step isolated resection of segment 1 of the liver using the hanging maneuver.

The caudate lobe can be the origin of primary liver tumours or the sole site of liver metastases. This lobe is anatomically divided into 3 parts: Spiegel's lobe (Couinaud's segment 1), paracaval portion (Couinaud's segment 9), and the caudate process. In this series of 4 cases, we provide a step-by-step description of a surgical technique variation that can be applied to resections of lesions localized in segment 1.

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.

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.

[Indications and results of liver retransplantations].

Liver retransplantation (re-LT) is the only therapeutic option for irreversible failure of the graft. It currently makes up 2.9% to 24.

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 View Article and Find Full Text PDF

Lessons learned from anatomic variants of the hepatic artery in 1,081 transplanted livers.

The aim of this study is to contribute our experience to the knowledge of the anatomic variations of the hepatic arterial supply. The surgical anatomy of the extrahepatic arterial vascularization was investigated prospectively in 1,081 donor cadaveric livers, transplanted at La Fe University Hospital from January 1991 to August 2004. The vascular anatomy of the hepatic grafts was classified according to Michels description (Am J Surg 1966;112:337-347) plus 2 variations.

Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts.

Liver grafts discarded for transplantation because of macrosteatosis can constitute a valuable source of human hepatocytes for in vitro metabolic and pharmacotoxicological studies or for therapeutic applications. A condition for using hepatocyte suspensions for these purposes is the preservation of their metabolic competence and, particularly, drug-metabolizing enzymes. A reduction in microsomal cytochrome P450 (P450) activities was observed in fatty livers (>40% steatosis) with respect to normal tissue.

Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts.

A major problem for the isolation and transplantation of hepatocytes is the lack of resources for obtaining viable hepatocytes. Improving this situation would enhance hepatic cell transplantation programs. Our objective was to evaluate the influence of the preservation solutions used during organ retrieval on the quality of hepatocytes isolated from liver tissue.

Acute biliary pancreatitis: does the pancreas change morphologically in the long term?

The objective of the study was to assess by means of magnetic resonance cholangiopancreatography whether acute biliary pancreatitis leads to alterations in pancreatic morphology and the main pancreatic duct; to establish whether such alterations are related to the severity of the acute episode and if they are to be considered as sequelae of the illness or on the contrary the findings constitute diagnostic morphological criteria of chronic pancreatitis. Forty patients with acute biliary pancreatitis were prospectively and consecutively studied, 15 female (37.5%) and 25 male (62.

Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours.

Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs).