Epidemiología y curso clínico de la hepatitis A en Cantabria antes y después del brote epidémico de junio 2016 / Epidemiology and clinical course of hepatitis A in Cantabria before and after the epidemic outbreak of June 2016

ANTECEDENTES Y OBJETIVOS: Desde junio de 2016 se han producido brotes de hepatitis A en diversos países europeos, afectando principalmente a hombres que tienen sexo con hombres (HSH). El objetivo del presente trabajo fue valorar su impacto clínico y epidemiológico en Cantabria. MATERIAL Y MÉTODOS: Se recogieron retrospectivamente todos los casos de hepatitis A diagnosticados en Cantabria entre enero de 2013 y septiembre de 2018. Se compararon dos periodos (enero 2013-mayo 2016 y junio 2016-septiembre 2018). RESULTADOS: Se diagnosticaron un total de 156 casos, objetivándose un aumento de la incidencia a partir de octubre de 2016. Con respecto al periodo 2013-2016, se observó una mayor proporción de varones (50,0 vs. 84,5%; p = 0,012) con una predominancia de la orientación sexual homosexual (80,6%) y una mayor frecuencia de transmisión sexual (0 vs. 48,3%; p = 0,061) en los pacientes del periodo 2016-2018. Desde el punto de vista clínico destacó que todos los casos de hepatitis grave ocurrieron en este último periodo. CONCLUSIONES: Nuestros resultados reafirman el elevado impacto clínico y epidemiológico del brote epidémico en Cantabria y ponen de relieve la necesaria optimización de las actuales medidas de prevención contra la hepatitis A

BACKGROUND AND OBJECTIVES: Since June 2016, there have been outbreaks of hepatitis A in various European countries, mainly affecting men who have sex with men (MSM). The aim of this study was to assess their clinical and epidemiological impact in Cantabria, Spain. MATERIAL AND METHODS: We retrospectively collected all cases of hepatitis A diagnosed in Cantabria between January 2013 and September 2018. We compared 2 periods: January 2013-May 2016 and June 2016-September 2018. RESULTS: A total of 156 cases were diagnosed, observing an increase in the incidence starting in October 2016. With regard to 2013-2016, we observed a higher proportion of men (50.0% vs. 84.5%; p=.012) with a predominance of the homosexual orientation (80.6%) and a higher rate of sexual transmission (0% vs. 48.3%; p=.061) for the patients in the 2016-2018 period. From the clinical standpoint, all cases of severe hepatitis occurred during this latter period. CONCLUSIONS: Our results reaffirm the high clinical and epidemiological impact of the epidemic outbreak in Cantabria and emphasizes the need for optimising the current prevention measures against hepatitis A

Effects of a high-fat-diet supplemented with probiotics and ω3-fatty acids on appetite regulatory neuropeptides and neurotransmitters in a pig model.

The pig is a valuable animal model to study obesity in humans due to the physiological similarity between humans and pigs in terms of digestive and associated metabolic processes. The dietary use of vegetal protein, probiotics and omega-3 fatty acids is recommended to control weight gain and to fight obesity-associated metabolic disorders. Likewise, there are recent reports on their beneficial effects on brain functions. The hypothalamus is the central part of the brain that regulates food intake by means of the production of food intake-regulatory hypothalamic neuropeptides, as neuropeptide Y (NPY), orexin A and pro-opiomelanocortin (POMC), and neurotransmitters, such as dopamine and serotonin. Other mesolimbic areas, such as the hippocampus, are also involved in the control of food intake. In this study, the effect of a high fat diet (HFD) alone or supplemented with these additives on brain neuropeptides and neurotransmitters was assessed in forty-three young pigs fed for 10 weeks with a control diet (T1), a high fat diet (HFD, T2), and HFD with vegetal protein supplemented with Bifidobacterium breve CECT8242 alone (T3) or in combination with omega-3 fatty acids (T4). A HFD provoked changes in regulatory neuropeptides and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and alterations mostly in the dopaminergic system in the ventral hippocampus. Supplementation of the HFD with B. breve CECT8242, especially in combination with omega-3 fatty acids, was able to partially reverse the effects of HFD. Correlations between productive and neurochemical parameters supported these findings. These results confirm that pigs are an appropriate animal model alternative to rodents for the study of the effects of HFD on weight gain and obesity. Furthermore, they indicate the potential benefits of probiotics and omega-3 fatty acids on brain function.

Epidemiology and clinical course of hepatitis A in Cantabria before and after the epidemic outbreak of June 2016. / Epidemiología y curso clínico de la hepatitis A en Cantabria antes y después del brote epidémico de junio 2016.

BACKGROUND AND OBJECTIVES: Since June 2016, there have been outbreaks of hepatitis A in various European countries, mainly affecting men who have sex with men (MSM). The aim of this study was to assess their clinical and epidemiological impact in Cantabria, Spain. MATERIAL AND METHODS: We retrospectively collected all cases of hepatitis A diagnosed in Cantabria between January 2013 and September 2018. We compared 2 periods: January 2013-May 2016 and June 2016-September 2018. RESULTS: A total of 156 cases were diagnosed, observing an increase in the incidence starting in October 2016. With regard to 2013-2016, we observed a higher proportion of men (50.0% vs. 84.5%; p=.012) with a predominance of the homosexual orientation (80.6%) and a higher rate of sexual transmission (0% vs. 48.3%; p=.061) for the patients in the 2016-2018 period. From the clinical standpoint, all cases of severe hepatitis occurred during this latter period. CONCLUSIONS: Our results reaffirm the high clinical and epidemiological impact of the epidemic outbreak in Cantabria and emphasizes the need for optimising the current prevention measures against hepatitis A.

Effect of environmental enrichment and herbal compound supplementation on physiological stress indicators (chromogranin A, cortisol and tumour necrosis factor-α) in growing pigs.

Stress response induces physiological, behavioural, immunological and biochemical changes that directly affect health and well-being. Provision of environmental enrichment and herbal compounds may reduce stress in current commercial pig husbandry systems. The aim of this study was to evaluate the effect of providing different environmental enrichment materials (EE) and a herbal compound (HC) on physiological indicators of acute and chronic stress in growing pigs (salivary cortisol and chromogranin A (CgA), hair cortisol and tumour necrosis factor-α (TNF-α)). Salivary cortisol and CgA have been reported as biomarkers basically of acute stress, whereas hair cortisol and TNF-α have been more related to chronic stress. For this purpose, eight groups of seven pigs each (14 pigs/treatment, 56 pigs in total) were used: (a) two EE groups, (b) two groups supplemented with HC, (c) two groups provided both with EE and HC and (d) two control groups. Samples of hair, saliva and blood were taken to measure cortisol (in hair and saliva), CgA (in saliva) and TNF-α (in blood) at three different times: before starting the experiment (T0), and after 1 (T1) or 2 months (T2) of providing the materials and herbal compound. No differences were found at T0 in salivary or hair cortisol, CgA or TNF-α, whilst at T2, the control group showed significant increased concentrations of CgA and hair cortisol, when compared with the rest of the treatments (P<0.001). These differences were significant at T1 only for CgA (P<0.001). Furthermore, an overall correlation was reported between hair cortisol and salivary CgA (r=0.48, P<0.001). These results support that providing enrichment material or an herbal compound may reduce stress in growing pigs. Furthermore, the results support that hair cortisol and CgA may be proper non-invasive tools to detect stress, specially associated with factors of chronic exposure.

Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation.

INTRODUCTION: Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. METHODS: Serum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. RESULTS: The concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. CONCLUSIONS: Our preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost.

De Novo Donor-Specific Anti-Human Leukocyte Antigen Antibody Detection in Long-Term Adult Liver Transplantation.

INTRODUCTION: Information about the consequences of de novo donor-specific anti-human leukocyte antigen (DSA) antibody development in the long term after adult liver transplantation (LT) is scarce. We conducted a cross-sectional study in LT patients with a follow-up of at least 6 years. METHODS: A total of 28 adult LT patients were included, with a median follow-up of 77 months (range, 63 to 96) and without preformed anti- human leukocyte antigen (HLA) antibodies prior to LT. The anti-HLA identification was performed with LABScreen Single Antigen, whereas the ability to fix the complement was demonstrated with C1q test (One Lambda). In both assays, a value >3.500 mean fluorescence intensity (MFI) was considered positive. The anti-HLA antibody specificities were compared with donor HLA antigens to confirm them as DSA. Hepatic fibrosis was assessed by transient elastography. RESULTS: In 5 patients (17.8%), de novo DSA were detected, all them against DQ locus. In all of these cases (100%) the complement fixation was confirmed by C1q binding. The grade of hepatic fibrosis in de novo DSA patients was significantly higher compared with No-DSA patients (13.2 ± 9.2 KPa vs 7.3 ± 3.7 KPa; P = .02). It is noteworthy that in both groups of patients the levels of liver function tests (LFT) at the time of the study were normal or near the normal range with no difference between patients with or without de novo DSA. CONCLUSIONS: Our preliminary results are consistent with those previously demonstrated in pediatric LT, where de novo DSA production and humoral response could contribute to the liver fibrosis observed in the long term after LT in pediatric patients with normal or near-normal LFT.

Activated Regulatory T Cells Expressing CD4(+)CD25(high)CD45RO(+)CD62L(+) Biomarkers Could Be a Risk Factor in Liver Allograft Rejection.

Activated regulatory T cells (aTregs) are nowadays a hot topic in organ transplantation to establish their role during acute rejection (AR) episodes. The aim of this multi-center study was to monitor the frequency of aTregs within the first year after transplantation in a cohort of first-time liver transplant recipients enrolled from 2010 to 2012. aTregs frequency was analyzed by means of flow cytometry. Patients who had AR showed higher levels of aTregs during first year after transplantation in comparison with patients who did not have higher levels. High levels of aTregs in liver recipients might be used as a biomarker of AR; however, further studies must be done to address the potential role of aTregs as biomarkers of AR in liver transplantation.

Use of an anti-GnRF vaccine to suppress estrus in crossbred Iberian female pigs.

Antibodies against GnRF elicited by vaccination with Improvac are expected to have the same effects on the gonads of female pigs as those observed in males and thus suppress estrus. The objective of this study was to evaluate whether a 3- or a 4-dose regimen of Improvac was effective in inducing and maintaining suppression of estrus in intact Iberian female pigs through 14 months of age. Sixty 18-week-old gilts were randomly assigned to one of the following three treatment groups: control (PBS injected), V3 (3-dose Improvac regimen), and V4 (4-dose Improvac regimen). Animals were tested for the presence of standing estrus in the presence of a boar three times per week until study completion at 60 weeks of age. Blood samples were regularly collected to determine the serum levels of anti-GnRF antibodies and progesterone. The weight and size of the uterus and the weight and activity of the ovaries were assessed at the time of euthanasia. For both treatment groups V3 and V4, a large reduction in the incidence of standing estrus was observed when compared to the control group (P < 0.0001). No significant differences between the V3 and V4 groups were observed. Both V3 and V4 groups had higher serum anti-GnRF antibody levels than the control group from 28 days after the first vaccination until the end of the study. In addition, both V3 and V4 groups had lower levels of progesterone than the control group from Day 112 until the end of the study (P < 0.0001 in all cases). Mean ovary weights at study end in treatment groups V3 and V4 were significantly lower (P < 0.0001) than those for the control group and not significantly different between the V3 and V4 groups. An onset of immunity of 2 weeks after the second vaccination and a long-lasting immunity of at least 20 weeks after the third vaccination were observed. In summary, both the 3-and 4-dose Improvac regimens were efficacious in reducing the incidence of standing estrus, serum progesterone levels, and the development of the uterus and ovaries.

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation.

The objective of this work was to study the postmortem evolution of potential biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress (total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase activity, CAT) in the Longissimus dorsi muscle of entire male ((Large White×Landrace)×Duroc) pigs subjected to different management treatments that may promote stress, such as mixing unfamiliar animals at the farm and/or during transport and lairage before slaughter. During the rearing period at the farm, five animals were never mixed after the initial formation of the experimental groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a common routine of being mixed with unfamiliar animals (mixed group at the farm, MF). Furthermore, two different treatments were used during the transport and lairage before slaughter: 10 pigs were not mixed (unmixed group during transport and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the lorry and during lairage (mixed group during transport and lairage, MTL). These mixing treatments were then combined into three pre-slaughter treatments - namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at short postmortem times (4 and 8 h; P<0.001), followed by an earlier depletion of the antioxidant activity at 24 h postmortem (P<0.05). We also found that mixing unfamiliar animals, both at the farm and during transport and lairage, triggers postmortem muscle autophagy, which showed an earlier activation (higher expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a decreasing pattern of this ratio along first 24 h postmortem) in the muscle tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of the muscle cells for counteracting induced stress. From these results, we propose that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle tissue within the first 24 h postmortem may help the detection of animal stress and its potential effect on the postmortem muscle metabolism.

Galectin-1 in stable liver transplant recipients.

INTRODUCTION: The achievement of a state of tolerance and minimization of the immunosuppressive load form part of the "Holy Grail" in solid organ transplantation. Galectin-1 recently has been described to be involved in the maintenance of a tolerant environment, but there is no evidence of its role in human liver transplantation. The aim of our study was to measure the serum levels of galectin-1 in stable liver transplant recipients. METHODS: Serum levels of galectin-1 were determined in 30 stable liver transplant recipients who had been free of rejection episodes for at least 8 years. Fifteen patients with an acute rejection episode and 34 healthy subjects were used as the control group. RESULTS: The concentrations of galectin-1 were significantly higher in stable liver transplant recipients compared with healthy subjects and with the acute rejection group. CONCLUSIONS: These preliminary results indicate that galectin-1 is upregulated in stable liver transplant recipients. Thus, our results extend the recent findings that galectin-1 may play an immune-suppressive role in liver transplantation. It remains to be established whether it might help to induce tolerance in liver transplantation.

Evaluation of the sustainability of contrasted pig farming systems: economy.

The aim of this paper is to present an efficient tool for evaluating the economy part of the sustainability of pig farming systems. The selected tool IDEA was tested on a sample of farms from 15 contrasted systems in Europe. A statistical analysis was carried out to check the capacity of the indicators to illustrate the variability of the population and to analyze which of these indicators contributed the most towards it. The scores obtained for the farms were consistent with the reality of pig production; the variable distribution showed an important variability of the sample. The principal component analysis and cluster analysis separated the sample into five subgroups, in which the six main indicators significantly differed, which underlines the robustness of the tool. The IDEA method was proven to be easily comprehensible, requiring few initial variables and with an efficient benchmarking system; all six indicators contributed to fully describe a varied and contrasted population.

Evaluation of the sustainability of contrasted pig farming systems: development of a market conformity tool for pork products based on technological quality traits.

A market conformity tool, based on technological meat quality parameters, was developed within the Q-PorkChains project, to be included in a global sustainability evaluation of pig farming systems. The specific objective of the market conformity tool was to define a scoring system based on the suitability of meat to elaborate the main pork products, according to their market shares based on industry requirements, in different pig farming systems. The tool was based on carcass and meat quality parameters that are commonly used for the assessment of technological quality, which provide representative and repeatable data and are easily measurable. They were the following: cold carcass weight; lean meat percentage; minimum subcutaneous back fat depth at m. gluteus medius level, 45 postmortem and ultimate pH (measured at 24-h postmortem) in m. longissimus lumborum and semimembranosus; meat colour; drip losses and intramuscular fat content in a m. longissimus sample. Five categories of pork products produced at large scale in Europe were considered in the study: fresh meat, cooked products, dry products, specialties and other meat products. For each of the studied farming systems, the technological meat quality requirements, as well as the market shares for each product category within farming system, were obtained from the literature and personal communications from experts. The tool resulted in an overall conformity score that enabled to discriminate among systems according to the degree of matching of the achieved carcass and meat quality with the requirements of the targeted market. In order to improve feasibility, the tool was simplified by selecting ultimate pH at m. longissimus or semimembranosus, minimum fat thickness measured at the left half carcass over m. gluteus medius and intramuscular fat content in a m. longissimus sample as iceberg indicators. The overall suitability scores calculated by using both the complete and the reduced tools presented good correlation and the results obtained were similar. The tool could be considered as robust enough to discriminate among different systems, since it was tested in a wide range of them. It also can be used to detect improvement opportunities to enhance sustainability of pig farming systems. The final objective of the study was achieved, since the market suitability tool could be used in an integrated sustainability analysis of pig farming systems.

Evaluation of the sustainability of contrasted pig farming systems: the procedure, the evaluated systems and the evaluation tools.

Although a few studies consider the sustainability of animal farming systems along the three classical main pillars (economy, environment and society), most studies on pig farming systems address only one of these pillars. The present paper is the introduction to a series of companion papers presenting the results of a study undertaken within the EU-supported project Q-PorkChains, aiming at building a comprehensive tool for the evaluation of pig farming systems, which is robust to accommodate the large variability of systems existing in Europe. The tool is mostly based on questions to farmers and comprises a total of 37 dimensions distributed along eight themes: Animal Welfare, Animal Health, Breeding Programmes, Environmental Sustainability, Meat Safety, Market Conformity, Economy and Working Conditions. The paper describes the procedure that was used for building the tool, using it on 15 contrasted pig farming systems and analysing the results. The evaluated systems are briefly described and a short overview of the dimensions is provided. Detailed descriptions of the theme-wise tools and results, as well as the results of an integrated evaluation, are available in the companion papers.

Evaluation of the sustainability of contrasted pig farming systems: integrated evaluation.

The aim of this paper is to present an approach for an integrated evaluation of the sustainability of pig farming systems, taking into account the three classical pillars: economy, environment and society. Eight sustainability themes were considered: Animal Welfare (AW), Animal Health (AH), Breeding Programmes (BP), Environment (EN), Meat Safety (MS), Market Conformity (MC), Economy (EC) and Working Conditions (WC). A total of 37 primary indicators were identified and used for the evaluation of 15 much contrasted pig farming systems in five EU countries. The results show that the eight themes were not redundant and all contributed to the observed variation between systems. The tool was very robust for highlighting the strengths and weaknesses of the systems along the eight themes that were considered. The number of primary indicators could be reduced from 37 to 18 with limited impact on the strengths/weaknesses profile of the individual systems. Integrating the eight theme evaluations into a single sustainability score is based on hypotheses or presumptions on the relative weights that should be given to the eight themes, which are very dependent on the context and on the purpose of the users of the tool. Therefore, the present paper does not have the ambition to provide a ready-for-use tool, rather to suggest an approach for the integrated evaluation of the sustainability of pig farming systems.

Majorcan Black Pig as a traditional pork production system: improvements in slaughterhouse procedures and elaboration of pork carpaccio as an alternative product.

The Majorcan Black Pig (MBP) was used as a model of differentiated traditional system within the Q-PorkChains project. The MBP farms were taken as an example of traditional system using a local breed which claims for high meat quality products. Welfare Quality® protocol was applied at the slaughterhouse and improvement strategies related to ante-mortem conditions and technological meat quality were defined. Pork carpaccio from MBP was elaborated to evaluate its sensory properties as an alternative to the existing MBP products. MBP tenderloins were better suited than those from pigs from a commercial breed to elaborate this product.

Serum levels of interleukin-9 during acute rejection in liver transplantation.

INTRODUCTION: Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection. METHODS: IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. RESULTS: The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation. CONCLUSIONS: These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection.

Interleukin-9 in stable liver transplant recipients.

INTRODUCTION: Interleukin-9 (IL-9) has recently been described to be involved in the maintenance of a tolerant environment, but there is no evidence of its role in human liver transplantation. The aim of our study was to measure the serum levels of IL-9 in stable liver transplant recipients and examine their influence on immunosuppressant load. METHODS: Serum IL-9 levels were determined in 34 healthy subjects and 30 stable liver transplant recipients who were free of rejection episodes for at least 8 years. The results were analyzed according to the blood levels of calcineurin inhibitors (CNIs) at the time of the study: 13 patients showed high concentrations of either cyclosporine or tacrolimus (high CNI: cyclosporine > 80 ng/mL or tacrolimus > 5 ng/mL) and another 17 patients showed low CNI levels. RESULTS: The concentrations of IL-9 were significantly higher among liver transplant recipients compared with healthy subjects. In addition, patients with low CNI blood levels showed higher serum levels of IL-9, an effect that was greater with tacrolimus, albeit not significantly. CONCLUSIONS: These preliminary results indicated that increased serum IL-9 concentrations accompanied a lower immunosuppressive load. It remains to be established whether this relates to induction of tolerance in liver transplantation.

Effect of housing system, slaughter weight and slaughter strategy on carcass and meat quality, sex organ development and androstenone and skatole levels in Duroc finished entire male pigs.

This study aimed at evaluating the effect of housing system (HS), slaughter weight (SW) and strategy (SS) on carcass a nd meat quality, sexual organ development and boar taint in entire males. Twelve pens of 10 pigs were used (two trials). Half of male pens were allowed visual contact with females (MF) and half with males (MM). Half MM or MF were slaughtered at 105 or 130 kg in trial 1, or penwise or by split marketing in trial 2 at 120 kg. Housing system showed no significant effect on carcass or meat quality. MF presented significantly longer testicles and heavier bulbourethral glands compared to MM. The distribution of androstenone and skatole levels was affected by SW but not by HS or SS, samples with androstenone >1 µg/g of the different groups falling within the range of 16 to 22%. All correlations between androstenone and sex organs were significant. Housing system and slaughter strategy did not reduce the risk of boar tainted carcasses.

Liver transplantation with donors older than 75 years.

INTRODUCTION: Orthotopic liver transplantation has shown successful results over the last years. For this reason there are increased numbers of patients on waiting lists. To expand the pool of liver donors, elderly donors have been used as a strategy. OBJECTIVE: We report our experience comparing donors of ≥ 75 years with younger ages for their characteristics, clinical outcomes, and survivals. METHODS: From January 2001 to December 2009, we performed 174 consecutive liver transplantation from cadaveric donors in 166 patients. During this period, we used 24 liver grafts from donors ≥ 75 years. We analyzed their outcomes retrospectively, describing donors and recipient characteristics and their clinical evolution. RESULTS: The mean follow-up time among the entire study population was 42 ± 39 months. We observed an overall survival of 68.3% with similar incidences in both groups: 83% in the younger versus 78% in the older group at 1 year, and 69% versus 63%, at 5 years respectively. Both groups showed similar lengths of intensive care unit stay, cold and warm ischemia times, and intraoperative transfusion requirements. The older group had a total operative time than was longer and fewer hypotensive episodes than the younger group. There were no significant differences in the rates of rejection and retransplantation between the groups. The use of older donor livers was associated with a significantly higher rate of poor initial graft function (P = .027), an increased number of reinterventions (P = .013) in the older donor group, as well as more frequent vascular and biliar complications, without reaching significance. CONCLUSION: Our data suggested that donor age alone did not engendered a survival disadvantage for graft or recipient. However, careful donor selection is needed to avoid additional risk factors that can increase the morbidity or mortality of the procedure.

A prospective, multicenter study of once-daily extended-release tacrolimus in de novo liver transplant recipients.

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.