Liver Transplantation In Spain Research Articles

POSB119 Economic Impact of Once-Daily MeltDose Extended-Release Tacrolimus (LCP-TAC) in Patients with Kidney or Liver Transplantation in Spain

Tacrolimus is an immunosuppression drug widely used for prevention of allograft rejection in kidney and liver transplantations. The once-daily extended-release tacrolimus (LCP-Tac) is a novel formulation for tacrolimus, differentiated by using the MeltDose technology which was designed to enhance the bioavailability of drugs with low water solubility. This study assessed the economic impact of the use LCP-Tac compared with other once-daily extended-release tacrolimus (PR-Tac) and with twice-daily immediate-release tacrolimus (IR-Tac) in patients with kidney or liver transplantation.

Expanding Indications of Liver Transplantation in Spain: Consensus Statement and Recommendations by the Spanish Society of Liver Transplantation.

The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain. A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the "Grading of Recommendations Assessment, Development, and Evaluation" system. The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient's age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer. We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario.

How Do Hepatologists Gain Access to Liver Transplant Units?

Liver transplantation has evolved from an experimental treatment to be considered as the most effective therapy for end-stage liver disease and selected cases of hepatocellular carcinoma. Transplant hepatologists must have specific knowledge and abilities to treat those patients who receive a liver transplant. In Spain, approximately 1100 liver transplants are performed each year, and most centers assume both postoperative care and long-term follow-up, which has led to a significant work load in liver transplant units. Despite previous attempts to establish an official training program in hepatology, the Spanish health system does not presently have a specific liver transplant training program to guarantee that future needs of physicians are covered. Collaboration between health authorities and scientific societies is required to guarantee adequate assistance to liver transplant recipients in the future.

Liver transplantation in Spain.

Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016 AASLD.

Survey of hemostasis management and transfusion in liver transplantation

ObjectiveTo determine the management of haemostasis and transfusion practice in the field of liver transplantation in Spain. MethodsA questionnaire was developed for physicians in anaesthesiology of all centres performing liver transplantation in Spain. The information required made reference to the 12 months prior to its distribution, from January 1 to December 31, 2011. ResultsData were collected from 24 centres in which liver transplantation is performed in Spain. Only 46% reported that they had protocols or practice guidelines for the management of haemostasis, and 83% of hospitals responded that they knew the percentage of transfused patients, but only 57% knew the mean transfusion. Regarding the degree of satisfaction with the management of haemostasis/coagulation, 50% said they were not satisfied. Thromboelastometry was used as an additional method of preoperative monitoring in only 8% of the centres and intra-operatively in one-third. Less than half (46%) of the centres performed preoperative correction of coagulation deficits based on conventional tests. The mean number of packed red cells used was ≤4 in 57% of centres. Consumption of fresh frozen plasma was highly variable, while 100% of centres consumed less than 4 pools of platelets per patient. ConclusionsThere is a wide variability in the management of haemostasis and transfusion practice among Spanish centres. There are no guidelines or they are not widely used. The mean use of transfused blood products remain high. There was a decrease in centres using new methods of monitoring.

Encuesta sobre el manejo perioperatorio de la hemostasia y transfusión en el trasplante hepático

ObjectiveTo determine the management of haemostasis and transfusion practice in the field of liver transplantation in Spain. MethodsA questionnaire was developed for physicians in anaesthesiology of all centres performing liver transplantation in Spain. The information required made reference to the 12 months prior to its distribution, from January 1 to December 31, 2011. ResultsData were collected from 24 centres in which liver transplantation is performed in Spain. Only 46% reported that they had protocols or practice guidelines for the management of haemostasis, and 83% of hospitals responded that they knew the percentage of transfused patients, but only 57% knew the mean transfusion. Regarding the degree of satisfaction with the management of haemostasis/coagulation, 50% said they were not satisfied. Thromboelastometry was used as an additional method of preoperative monitoring in only 8% of the centres and intra-operatively in one-third. Less than half (46%) of the centres performed preoperative correction of coagulation deficits based on conventional tests. The mean number of packed red cells used was ≤4 in 57% of centres. Consumption of fresh frozen plasma was highly variable, while 100% of centres consumed less than 4 pools of platelets per patient. ConclusionsThere is a wide variability in the management of haemostasis and transfusion practice among Spanish centres. There are no guidelines or they are not widely used. The mean use of transfused blood products remain high. There was a decrease in centres using new methods of monitoring.

Activity and results of liver transplantation in Spain during 1984-2012. Analysis of the Spanish Liver Transplant Registry

Background and objectiveLiver transplantation (LT) is a proven effective treatment of severe liver disease. The aim of this paper is to analyze the results of LT in Spain during the period 1984–2012. Patients and methodWe analyze the results of the database of Spanish Liver Transplant Registry. ResultsA total of 20,288 transplants were performed in 18,568 patients. The median age of the donor and recipient increased during the analysis period: 25 years (95% confidence interval [95% CI] 18–40) and 47 years (95% CI 34–55), respectively, in the period 1984–1994 compared to 59 years (95% CI 33–65; P<.05) and 55 years (95% CI 48–61; P<.01), respectively, in the period 2010–2012. The most frequent indications were liver cirrhosis (63.18%) and hepatocellular carcinoma (19.62%). The overall patient and graft survival was respectively 85.1 and 77.8% in the first year, 72.6 and 63.5% the fifth year and 62 and 52.6% in the tenth year. First year patients and graft survival increased respectively from 77.8 and 66.3% in the period 1984–1994 to 88.5 and 83% in 2010–2012 (P<.01). Donor and recipient age, etiology of underlying disease, and hepatitis C virus serological status, were factors associated with decreased survival in univariate and multivariate analysis. ConclusionsResults of LT improved significantly over the review period, despite a progressive increase in donor and recipient age.

Statistical Quality Control Charts for Liver Transplant Process Indicators: Evaluation of a Single-Center Experience

Liver transplantation, the best option for many end-stage liver diseases, is indicated in more candidates than the donor availability. In this situation, this demanding treatment must achieve excellence, accessibility and patient satisfaction to be ethical, scientific, and efficient. The current consensus of quality measurements promoted by the Sociedad Española de Trasplante Hepático (SETH) seeks to depict criteria, indicators, and standards for liver transplantation in Spain. According to this recommendation, the Canary Islands liver program has studied its experience. We separated the 411 cadaveric transplants performed in the last 15 years into 2 groups: The first 100 and the other 311. The 8 criteria of SETH 2010 were correctly fulfilled. In most indicators, the outcomes were favorable, with an actuarial survivals at 1, 3, 5, and 10 years of 84%, 79%, 76%, and 65%, respectively; excellent results in retransplant rates (early 0.56% and long-term 5.9%), primary nonfunction rate (0.43%), waiting list mortality (13.34%), and patient satisfaction (91.5%). On the other hand, some indicators of mortality were worse as perioperative, postoperative, and early mortality with normal graft function and reoperation rate. After the analyses of the series with statistical quality control charts, we observed an improvement in all indicators, even in the apparently worst, early mortality with normal graft functions in a stable program. Such results helped us to discover specific areas to improve the program. The application of the quality measurement, as SETH consensus recommends, has shown in our study that despite being a consuming time process, it is a useful tool.

Prevalence of Hepatitis B and A Virus Markers and Vaccination Indication in Cirrhotic Patients Evaluated for Liver Transplantation in Spain

In the absence of immunity, vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic liver disease and those evaluated for liver transplantation (OLT) HAV and HBV infections after OLT which are frequent in this setting, are associated with a worse prognosis. The aim of this study was to estimate the need for vaccination against HBV and HAV among cirrhotic patients who were candidates for OLT and associations with gender, age, and etiologic factors. HBV and HAV serological markers HBsAg, anti-HBc, antiHBs, immunoglobulin G (IgG)-anti-HAV were investigated among 568 patients, including 75% men. The overall mean age was 53.6 ± 8.9 years range 17–69, and 20% were diabetic. This etiologies were alcohol (68%), hepatitis C virus (35%) or other causes (10.4%). Child-Pugh classes were: A (26%), B (44%), and C (30%). In contrast with 359 patients (63.2%) who had negative HBV markers, 209 (36.8%) were positive: HBsAg (+), 43 (7.6%), isolated anti-HBc (+), 57 (10%), isolated anti-HBs (+), 19 (3.3%), anti-HBc (+)/anti-HBs (+), 90 (15.8%). HBV vaccine indication was performed in 416 patients (73.2%) who either had negative HBV markers or isolated anti-HBc (+). It was more frequently performed in women (82.3% versus 70.3%, P = .005), albeit with no differences according to age or etiology. There were only 8.2% (44/538) IgG-anti-HAV-negative, an indication for vaccination against HAV, which was more frequent affecting patients who were younger [≤45 years (27.6%), 46–55 (7.2%), >55 (2.6%); P < .0001)]; nondiabetic (9.5% versus 2.8%, P = .023); nonalcoholic (11.4% versus 6.6%, P = .056); and displayed negative HBV markers (10.2% versus 4.6%, P = .023). Only three patients with IgG-anti- HAV (−) were over 60 years. In conclusion, there is a frequent indication for HBV vaccination among cirrhotic and especially HAV vaccine for under 45 year old patients undergoing evaluation for OLT.

Prevalence of Hepatitis A and B Markers and Vaccine Indication in Cirrhotic Patients Evaluated for Liver Transplantation in Spain

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (−), 11.5%; anti-HBc (−)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients ≤45 years). In conclusion, there are frequent indication, for HBV vaccine among cirrhotic patients evaluated for liver transplantation, as is time for HAV vaccine, especially among patients younger than 45 years of age.

Liver Transplantation: Experience With Our First 100 Cases

Objectives Our goal was to evaluate the results of the first 100 liver transplants performed in our institution. Methods We retrospectively analyzed the first 100 liver transplants undertaken in adults from November 2001 to August 2005. Results The mean age of the recipients was 50 years (20 to 69) and 73% were men. The mean waiting time was 35 days. The mean age of the donors was 60 years (15 to 87), and 60% were men. One-year patient and graft survival rates were 93% and 90%, respectively. Three-year patient and graft survival rates were 85% and 82%, respectively. The need for retransplantation was 3%. Surgical complications included hepatic artery stenoses, 2%; hepatic artery thromboses, 2%; biliary leaks, 6%; and biliary stenoses, 14%. Conclusions These results are no different from the overall results for liver transplantation in Spain during the same period.

Disparities in access to liver transplantation in Spain

The maintenance of an equitable system for access to transplantation is a matter of concern to all professionals involved in this field. Any national system must ensure equity. The rates of indication for liver transplantation have been reviewed for all Spanish regions. The time to transplantation was evaluated with respect to different recipient characteristics and donor rates. The indication rates for liver transplantation are similar in the different countries with liver transplant programs but are far from similar among different regions in Spain. This suggests that there is not equity in the access to liver transplantation. A review of the factors affecting the waiting times to transplantation after being registered for the waiting list shows that some groups of patients are currently waiting less time than others. Shorter waiting times occur in patients of the AB group, children, patients with hepatocarcinoma, and patients living in the zone of Valencia, despite similar organ donation rates in all transplant zones. Neither the rate nor the probability of liver transplantation is affected exclusively by the organ donation rate in Spain but also depends on the number of patients admitted to the waiting list. Despite the existence of an organ allocation system that is center-oriented, liver patients are receiving grafts mainly based on the severity of the illness, because clearance rates from the waiting list of both dead patients and grafted patients are the same.

Live liver donation: a prospective analysis of exclusion criteria for healthy and potential donors

Introduction Living donor liver transplantation represents a controversial option to increase the donor pool. Design Prospective and descriptive clinical study. Objective (1) To identify risk factors (exclusion criteria) for live donation; (2) to determine the rate of recipients that benefit from a living donor. Methods Between May 1995 (first adult-to-adult living donor liver transplantation in Spain) and November 2002, we evaluated 74 healthy volunteers and performed 12 living donor liver transplants (no donor mortality). Results All actual donors and volunteers are alive and healthy. After a mean time of 3.2 ± 0.5 weeks, 72% of potential donors were considered unsuitable for live donation. Exclusion criteria were grouped in three categories: (1°) donor safety reasons (68%); (2°): ABO mismatch (17%) and (3°): cadaveric graft transplantation (15%). Consequently, just 43.7% of the recipients presenting to us with a potential living donor, did finally benefit from these organs. The mortality rate was 8.3% for 43 recipients presenting with a living donor in comparison to 15% for those who did not (321 recipients between May 1995 and November 2001). Conclusions ALDLT can benefit a significant number of recipients on the waiting list (43.7% of those presenting with a donor). The most frequent exclusion criteria concern donor safety, namely, unsuspected chronic liver diseases and unsuspected thrombophilic disorders.