Nuestros investigadores

José Ignacio Herrero Santos

Publicaciones científicas más recientes (desde 2010)

Autores: Herrero, José Ignacio, (Autor de correspondencia); Lucena, Juan Felipe; Quiroga, Jorge Augusto;
Revista: BMC MEDICAL EDUCATION
ISSN 1472-6920  Vol. 19  2019  págs. 72
Autores: Yuste, JR, (Autor de correspondencia); Serrano-Alonso, M; Carmona, Francisco de Asís; et al.
Revista: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
ISSN 0305-7453  Vol. 74  Nº 9  2019  págs. 2817 - 2819
Autores: Baroja-Mazo, A., (Autor de correspondencia); Revilla-Nuin, B. ; de Bejar, A.; et al.
Revista: AMERICAN JOURNAL OF TRANSPLANTATION
ISSN 1600-6135  Vol. 19  Nº 1  2019  págs. 48 - 61
The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A(2)R) in the induction of clinical tolerance after liver transplant. The action of extracellular nucleotides in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39-CD73-A(2)R axis were compared between tolerant and nontolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the enzyme responsible for the degradation of ADO, adenosine deaminase, was higher in tolerant patients with respect to the nontolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplant tolerance.
Autores: Herrero, José Ignacio, (Autor de correspondencia); Lucena, Juan Felipe; Quiroga, Jorge Augusto;
Revista: BMC MEDICAL EDUCATION
ISSN 1472-6920  Vol. 19  Nº 1  2019  págs. Article number 42
Background: Writing multiple choice questions may be a valuable tool for medical education. We asked medical students to generate multiple choice questions and studied its effect on their exams. We hypothesized that students generating questions would improve their learning. Methods: We randomized students in their second and third years at the School of Medicine to write four multiple choice questions on two different sections of General Pathology (Immunopathology and Electrolyte and acid-base status; second year) and Pathophysiology (Blood and Respiratory system; third year). We analyzed whether students writing questions on a section had better results in the exam test in that section than the rest of the students. Results: Seventy-five (38.2%) students wrote questions for General Pathology and 109 (47.6%) for Pathophysiology. Students that wrote questions obtained significantly better results in the exam than those who did not. In General Pathology, students who wrote questions about Immunopathology obtained better results in that section than those who wrote questions about the other section (5.13 versus 3.86 over 10; P¿=¿0.03). In Pathophysiology, the differences between both groups were not significant, but students who wrote good questions about Respiratory system obtained better results in that section than those who wrote good questions about Blood (6.07 versus 4.28 over 10; P¿=¿0.015). Male students wrote good questions in Pathophysiology more frequently than female students (28.1% versus 10.4%; P¿=¿0.02). Conclusions: The writing of multiple choice questions by medical students may improve their learning. A gender effect may also influence this intervention. Future investigations should refine its potential role in teaching.
Autores: Zabaleta, Aintzane; Sangro, Paloma; et al.
Revista: TRANSPLANTATION PROCEEDINGS
ISSN 0041-1345  Vol. 51  Nº 1  2019  págs. 77 - 79
Autores: Cantero, Irene; Elorz, Mariana; Abete, Itziar; et al.
Revista: INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
ISSN 1449-1907  Vol. 16  Nº 1  2019  págs. 75 - 83
Introduction: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. Objective: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. Materials and methods: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty Liver Index (FLI) were evaluated. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193. Results: The subjects with more severe liver disease were found to have worse metabolic parameters. Positive associations between MRI with inflammatory and insulin biomarkers were found. A linear regression model including ALT, RBP4 and HOMA-IR was able to explain 40.9% of the variability in fat content by MRI. In ROC analyses a combination panel formed of ALT, HOMA-IR and RBP4 followed by ultrasonography, ALT and metabolomic test showed the major predictive ability (77.3%, 74.6%, 74.3% and 71.1%, respectively) for liver fat content. Conclusions: A panel combination including routine blood markers linked to insulin resistance showed highest associations with MRI considered as a gold standard for determining liver fat content. This combination of tests can facilitate the diagnosis of early stages of non-alcoholic liver disease thereby avoiding other invasive and expensive methods.
Autores: Serrano-Alonso, M; Guillén-Grima, F; Martín, Paloma Leticia; et al.
Revista: TRANSPLANT INFECTIOUS DISEASE
ISSN 1398-2273  Vol. 20  Nº 3  2018  págs. e12873
Background: Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. The role of secondary CMV prophylaxis in this population remains unclear. Methods: Retrospective cohort study in a single center. SOT recipients treated for CMV infection from 2007 to 2014 were studied to determine the efficacy and safety of secondary prophylaxis and its impact on graft loss and mortality. The outcome variable was CMV replication in the first 3 months after the end of therapy. Secondary variables were crude mortality and graft lost censored at 5 years after transplantation. Propensity score for the use of secondary prophylaxis was used to control selection bias. Results: Of the 126 treated patients, 103 (83.1%) received CMV secondary prophylaxis. CMV relapse occurred in 44 (35.5%) patients. The use of secondary prophylaxis was not associated with fewer relapses (34.0% in patients with prophylaxis vs. 42.9% in those without prophylaxis, p= 0.29).After a mean follow-up of 32.1 months, graft loss was not different between both groups but patient mortality was significantly lower in patients who received secondary prophylaxis (5.8% vs. 28.6%, p= 0.003). Conclusion: Secondary prophylaxis did not prevent CMV infection relapse but it was associated with improved patient survival.
Autores: Galarregui, C.; Zulet, María de los Ángeles; Cantero, Irene; et al.
Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN 1422-0067  Vol. 19  Nº 11  2018  págs. 3662
Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet-disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 +/- 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.
Autores: Alegre, Félix; Rifón, José Juan; et al.
Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN 1130-0108  Vol. 110  Nº 11  2018  págs. 734 - 736
We present the case of a liver transplant (LT) recipient donor who developed graft versus host disease (GVHD).The main features were cutaneous rash, diarrhea and pancytopenia. Mesenchymal cells were administered as part of the treatment. This is the first case of a patient with GVHD after LT reported to date. Despite the treatment, there was no improvement in aplasia or gastrointestinal symptoms and the patient died due to a disseminated infection.
Autores: Herrero, José Ignacio, (Autor de correspondencia); Cuervas-Mons, V.; Gomez-Bravo, M. A.; et al.
Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN 1130-0108  Vol. 110  Nº 9  2018  págs. 538 - 543
Introduction: chronic kidney disease is a frequent complication after liver transplantation. The use of calcineurin inhibitors is one of the causes of this complication. Current immunsuppression regimens that reduce the use of calcineurin inhibitors may be associated with an improved preservation of renal function. Objective: the study aimed to assess the evolution of renal function after liver transplantation in the current routine clinical practice. Methods: an observational, prospective, multicenter study in adult liver transplant recipients was performed. Two hundred and thirty patients with a good renal function before transplantation were assessed six months post-transplantation (baseline) and every six months until month 30. Results: at baseline, 32% of the patients had a reduction in the glomerular filtration rate below 60 ml/min/1.73 m(2). The mean glomerular filtration rate increased from 72.3 to 75.6 ml/min/1.73 m(2) at baseline and month 30 respectively (p < 0.01). The mean serum creatinine levels (mg/dl) decreased from 1.13 to 1.09 (p < 0.01). The percentage of patients with stage 3 chronic kidney disease decreased from 31.7% to 26.4%, whereas the percentage of patients with stage 4 remained unchanged (0.4% at baseline and 0.5% at month 30). No patients progressed to end-stage kidney disease that required dialysis or renal transplantation. Conclusion: in the routine clinical practice, a moderate deterioration of renal function is frequent after liver transplantation. However, advanced chronic kidney disease is infrequent in patients with a good pre-transplant renal function.
Autores: Manzardo, C.; Londono, M. C.; Castells, L.; et al.
Revista: AMERICAN JOURNAL OF TRANSPLANTATION
ISSN 1600-6135  Vol. 18  Nº 10  2018  págs. 2513 - 2522
Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/mu L. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF+LDVRBV (34%), SOF+SMV +/- RBV (31%), SOF+DCV +/- RBV (27%), SMV+DCV +/- RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P=.239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P=.093) and genotype 4 (P=.088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients. Direct-acting antivirals against HCV offer a very high and similar efficacy and safety in HIV-positive and HIV-negative liver transplant recipients.
Autores: Herrero, José Ignacio, (Autor de correspondencia); Panizo, Carlos Manuel;
Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN 1130-0108  Vol. 110  Nº 2  2018  págs. 131 - 132
Autores: Cantero, Irene; Abete, Itziar; Marin-Alejandre, A. ; et al.
Revista: ANNALS OF NUTRITION AND METABOLISM
ISSN 0250-6807  Vol. 73  Nº Supl 2  2018  págs. 45
Autores: D'Avola, Delia; Cuervas Mons, V.; Marti, J.; et al.
Revista: LIVER TRANSPLANTATION
ISSN 1527-6465  Vol. 23  Nº 4  2017  págs. 498 - 509
Cardiovascular (CV) diseases are recognized longterm causes of death after liver transplantation (LT). The objective of this multicenter study was to analyze the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 LT recipients along 5 years after LT. The influence of baseline variables on survival, morbidity, and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow-up. Most CV events (39%) occurred in the first year after LT. Preexisting CV risk factors such as age, pre-LT CV events, diabetes, metabolic syndrome, and hyperuricemia, and mycophenolate-free immunosuppressive therapy, increased post-LT CV morbidity and mortality. The development of new-onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of posttransplant diabetes, whereas cyclosporine increased the risk of arterial hypertension, dyslipidemia, and metabolic syndrome. In conclusion, CV complications and CV mortality are frequent in LT recipients. Preexisting CV risk factors, immunosuppressive drugs, but also the early new onset of obesity and dyslipidemia after LT play an important role on late CV complications. A strict metabolic control in the immediate post-LT period is advisable for improving CV risk of LT recipients. Liver Transplantation 23 498-509 2017 AASLD.
Autores: Perello, C.; Carrion, J. A.; Ruiz-Antoran, B.; et al.
Revista: JOURNAL OF VIRAL HEPATITIS
ISSN 1352-0504  Vol. 24  Nº 3  2017  págs. 226 - 237
Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir +/- dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naive and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naive. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.
Autores: Martínez, Diego; D'Avola, Delia; et al.
Revista: ANNALS OF TRANSPLANTATION
ISSN 1425-9524  Vol. 22  2017  págs. 141 - 147
Background: Immunosuppression increases the risk of malignancy in liver transplant recipients. The potential impact of mycophenolate mofetil monotherapy on this risk has not been studied. Material/Methods: The incidence and risk factors for de novo malignancies of 392 liver transplant recipients with a survival higher than 3 months and a mean follow-up of 8.5 years were studied. Results: De novo malignancies were diagnosed in 126 patients (32.1%) (64 non-melanoma skin cancer and 81 other malignancies). Sixty-nine patients (18.1%) stopped receiving calcineurin inhibitors and were maintained on mycophenolate mofetil monotherapy. The proportion of time on mycophenolate mofetil monotherapy (obtained after dividing the time on monotherapy by the time until diagnosis of neoplasia/last follow-up) was independently associated with a lower risk of de novo malignancy (HR: 0.16, 95% CI: 0.05-0.48; P=0.001), non-melanoma skin cancer (HR: 0.17, 95% CI: 0.03-0.79; P=0.024), and other malignancies (HR: 0.23, 95% CI: 0.07-0.77; P=0.017). Older age and male sex were also associated with a higher risk of malignancy, and transplantation for hepatocellular carcinoma increased the risk of non-melanoma skin cancer. Conclusions: Mycophenolate mofetil monotherapy is associated with a lower risk of cancer in liver transplant recipients compared with maintenance immunosuppression with calcineurin inhibitors.
Autores: Rotellar, Fernando; Pardo, Fernando; Benito, Alberto; et al.
Revista: TRANSPLANTATION
ISSN 0041-1337  Vol. 101  Nº 3  2017  págs. 548 - 554
Background. The pure laparoscopic approach in right hepatectomy (LRH) for living donor liver transplantation (LDLT) is a controversial issue. Some authors have reported the procedure to be feasible but surgical outcomes and impact on short and longterm morbidity rates are yet to be determined. The aim of this study is to present the results of a preliminary 5 consecutive cases series of LRH for LDLT and to compare it with a successive cohort of open right hepatectomies (ORH) for LDLT. Methods. From May 2013 to October 2015, 5 consecutive donors underwent LRH for LDLT in our center. The previous last 10 ORH for LDLT were selected for comparison. Special care was taken to include all adverse events. Each patient's complications were graded with the Clavien-Dindo Classification and scored with the Comprehensive Complication Index. Results. All 5 consecutive donors completed a pure laparoscopic procedure. All allografts (open and laparoscopically procured) were successfully transplanted with no primary graft failures. Only 2 Clavien-Dindo Grade-I complications occurred in the LRH donors, while ORH donors had 10 Grade I, 2 Grade II and 1 Grade IIIa complications in the short term (< 3 months). In the long term (6-12 months follow-up), LRH donors had a significant lower incidence of complications (Comprehensive Complication Index: 1.74; SD, 3891 vs 15.2 SD; 8.618; P = 0.006). Conclusions. In our experience, LRH for LDLT is a feasible procedure. Further comparative series may support our preliminary findings of reduced incidence and severity of complications as compared with the open approach.
Autores: Fernández Carrillo, C.; Lens, S.; Llop, E.; et al.
Revista: HEPATOLOGY
ISSN 0270-9139  Vol. 65  Nº 6  2017  págs. 1810 - 1822
Direct-acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. However, fewer data are available in patients with more advanced liver disease. Our retrospective, noninterventional, national, multicenter study in patients from the Spanish Hepa-C registry investigated the effectiveness and safety of interferon-free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered). Patients transplanted during treatment or within 12 weeks of completing treatment were excluded. Among 843 patients with cirrhosis (Child-Turcotte-Pugh [CTP] class A, n = 564; CTP class B/C, n = 175), 90% achieved sustained virologic response 12 weeks after treatment (SVR12). Significant differences in SVR12 and relapse rates were observed between CTP class A and CTP class B/C patients (94% versus 78%, and 4% versus 14%, respectively; both P < 0.001). Serious adverse events (SAEs) were more common in CTP class B/C versus CTP class A patients (50% versus 12%, respectively; P < 0.001). Incident decompensation was the most common serious adverse event (7% overall). Death rate during the study period was 16/843 (2%), significantly higher among CTP class B/C versus CTP class A patients (6.4% versus 0.9%; P < 0.001). Baseline Model for End-Stage Liver Disease (MELD) score alone (cut-off 18) was the best predictor of survival. Conclusion: Patients with decompensated cirrhosis receiving DAAs present lower response rates and experience more SAEs. In this setting, a MELD score >= 18 may help clinicians to identify those patients with a higher risk of complications and to individualize treatment decisions.
Autores: Revilla-Nuin, B. ; de Bejar, A.; Martinez-Alarcon, L. ; et al.
Revista: LIVER TRANSPLANTATION
ISSN 1527-6465  Vol. 23  Nº 7  2017  págs. 933 - 945
Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplantation (LT) patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on LT tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) LT recipients by cellular, genetic, and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the forkhead box P3 (FOXP3) regulatory T cell-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs. Tol patients presented a different signature of Treg subset markers compared with non-Tol patients with increased expression of HELIOS and FOXP3 and a higher proportion of latency-associated peptide (LAP)(+) Tregs and CD45RA(-) human leukocyte antigen D related (HLA-DR)(+) activated effector-memory Tregs. The expression of miR95, miR24, miR31, miR146a, and miR155 was higher in Tol than in non-Tol patients and was positively correlated with activated Treg markers. In conclusion, these data suggest that activated effector-memory Tregs and a TSDR-demethylation state of Tregs may play a role in the complex system of regulation of LT tolerance. In addition, we describe a set of miRNAs differentially expressed in human LT Tol patients providing suggestive evidence that miRNAs are implied in the preservation of self-tolerance as mediated by Tregs.
Autores: Martínez, Nicolás; Alfonso, Ana; Rifón, José Juan; et al.
Revista: EUROPEAN JOURNAL OF HAEMATOLOGY
ISSN 0902-4441  Vol. 98  Nº 1  2017  págs. 38 - 43
This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.
Autores: Elosegui-Artola, A.; D'Avola, Delia; Carte, Beatriz; et al.
Revista: ONCOTARGET
ISSN 1949-2553  Vol. 8  Nº 25  2017  págs. 40967 - 40981
The identification of new targets for systemic therapy of hepatocellular carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB catalyzes the N-alpha-terminal acetylation of 15% of the human proteome and that this action is necessary for proper actin cytoskeleton structure and function. In tumors, cytoskeletal changes influence motility, invasion, survival, cell growth and tumor progression, making the cytoskeleton a very attractive antitumor target. Here, we show that hNatB subunits are upregulated in in over 59% HCC tumors compared to non-tumor tissue and that this upregulation is associated with microscopic vascular invasion. We found that hNatB silencing blocks proliferation and tumor formation in HCC cell lines in association with hampered DNA synthesis and impaired progression through the S and the G2/M phases. Growth inhibition is mediated by the degradation of two hNatB substrates, tropomyosin and CDK2, which occurs when these proteins lack N-alpha-terminal acetylation. In addition, hNatB inhibition disrupts the actin cytoskeleton, focal adhesions and tight/adherens junctions, abrogating two proliferative signaling pathways, Hippo/YAP and ERK1/2. Therefore, inhibition of NatB activity represents an interesting new approach to treating HCC by blocking cell proliferation and disrupting actin cytoskeleton function.
Autores: D'Avola, Delia; Carmona, Francisco de Asís; et al.
Revista: TRANSLATIONAL RESEARCH
ISSN 1931-5244  Vol. 188  2017  págs. 80-91.e2
The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ¿8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount
Autores: D'Avola, Delia; Fernández-Ruiz, Veronica; Carmona, Francisco de Asís; et al.
Revista: TRANSLATIONAL RESEARCH
ISSN 1931-5244  Vol. 188  2017  págs. 80 - 91.e2
The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh [greater than or equal to]8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation.
Autores: Salcedo, M.; Prieto, M.; Castells, L.; et al.
Revista: TRANSPLANT INTERNATIONAL
ISSN 0934-0874  Vol. 30  Nº 10  2017  págs. 1041 - 1050
Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155-0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061-1.218) were predictors of death. DCV-based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response.
Autores: Agüero, F.; Forner, A.; Valdivieso, A.; et al.
Revista: LIVER TRANSPLANTATION
ISSN 1527-6465  Vol. 23  Nº 5  2017  págs. 645 - 651
There is a lack of data on incidental hepatocellular carcinoma (iHCC) in the setting of liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients. This study aims to describe the frequency, histopathological characteristics, and outcomes of HIV+ LT recipients with iHCC from a Spanish multicenter cohort in comparison with a matched cohort of LT patients without HIV infection. A total of 15 (6%) out of 271 patients with HIV infection who received LT in Spain from 2002 to 2012 and 38 (5%) out of the 811 HIV- counterparts presented iHCC in liver explants (P = 0.58). Patients with iHCC constitute the present study population. All patients also had hepatitis C virus (HCV)-related cirrhosis. There were no significant differences in histopathological features of iHCC between the 2 groups. Most patients showed a small number and size of tumoral nodules, and few patients had satellite nodules, microvascular invasion, or poorly differentiated tumors. After a median follow-up of 49 months, no patient developed hepatocellular carcinoma (HCC) recurrence after LT. HIV+ LT recipients tended to have lower survival than their HIV- counterparts at 1 (73% versus 92%), 3 (67% versus 84%), and 5 years (50% versus 80%; P = 0.06). There was also a trend to a higher frequency of HCV recurrence as a cause of death in the former (33% versus 10%; P = 0.097). In conclusion, among LT recipients for HCV-related cirrhosis, the incidence and histopathological features of iHCC in HIV+ and HIV- patients were similar. However, post-LT survival was lower in HIV+ patients probably because of a more aggressive HCV recurrence. Liver Transplantation 23 645-651 2017 AASLD.
Autores: Pascasio, J. M. ; Vinaixa, C. ; Ferrer, M. T. ; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 66  Nº 1 Supl.  2017  págs. S186
Autores: Pascual, J.; Royuela, A.; Fernández, A. M.; et al.
Revista: TRANSPLANT INFECTIOUS DISEASE
ISSN 1398-2273  Vol. 18  Nº 6  2016  págs. 819 - 831
Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.
Autores: D'Avola, Delia; Carmona, Francisco de Asís; Miriam Méndez; et al.
Revista: TRANSLATIONAL RESEARCH
ISSN 1931-5244  Vol. 188  Nº S1931-5244(16)00063-3  2016  págs. 80 - 91
The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ¿8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount
Autores: Agüero, F.; Forner, A.; Manzardo, C.; et al.
Revista: HEPATOLOGY
ISSN 0270-9139  Vol. 63  Nº 2  2016  págs. 488 - 498
The impact of human immunodeficiency virus (HIV) infection on patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) is uncertain. This study aimed to assess the outcome of a prospective Spanish nationwide cohort of HIV-infected patients undergoing LT for HCC (2002-2014). These patients were matched (age, gender, year of LT, center, and hepatitis C virus (HCV) or hepatitis B virus infection) with non-HIV-infected controls (1:3 ratio). Patients with incidental HCC were excluded. Seventy-four HIV-infected patients and 222 non-HIV-infected patients were included. All patients had cirrhosis, mostly due to HCV infection (92%). HIV-infected patients were younger (47 versus 51 years) and had undetectable HCV RNA at LT (19% versus 9%) more frequently than non-HIV-infected patients. No significant differences were detected between HIV-infected and non-HIV-infected recipients in the radiological characteristics of HCC at enlisting or in the histopathological findings for HCC in the explanted liver. Survival at 1, 3, and 5 years for HIV-infected versus non-HIV-infected patients was 88% versus 90%, 78% versus 78%, and 67% versus 73% (P = 0.779), respectively. HCV infection (hazard ratio = 7.90, 95% confidence interval 1.07-56.82) and maximum nodule diameter >3 cm in the explanted liver (hazard ratio = 1.72, 95% confidence interval 1.02-2.89) were independently associated with mortality in the whole series. HCC recurred in 12 HIV-infected patients (16%) and 32 non-HIV-infected patients (14%), with a probability of 4% versus 5% at 1 year, 18% versus 12% at 3 years, and 20% versus 19% at 5 years (P = 0.904). Microscopic vascular invasion (hazard ratio = 3.40, 95% confidence interval 1.34-8.64) was the only factor independently associated with HCC recurrence. Conclusions: HIV infection had no impact on recurrence of HCC or survival after LT. Our results support the indication of LT in HIV-infected patients with HCC.
Autores: Conchillo, María de los Ángeles; et al.
Revista: EUROPEAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
ISSN 0954-691X  Vol. 28  Nº 2  2016  págs. 139 - 145
Objective Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. Patients and methods We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. Results REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, â-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P< 0.05), nonprotein respiratory quotient (P< 0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P< 0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. Conclusion Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.
Autores: Plaza, M. M. S.; Vinaixa, C.; Fuste, L. C.; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 64  Nº 2, Supl.  2016  págs. S547
Autores: Fernández Carrillo, C.; Lens, S.; Llop, E.; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 64  Nº Supl. 2  2016  págs. S133
Autores: Sanchez-Antolin, G.; Testillano, M. ; Prieto, M. ; et al.
Revista: HEPATOLOGY
ISSN 0270-9139  Vol. 64  Nº Supl. 1  2016  págs. 113A
Autores: Prieto, M.; Fernández, I.; Londoño, M. C.; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 64  Nº 2, Supl.  2016  págs. S794 - S795
Autores: Pascasio, J. M.; Vinaixa, C.; Ferrer, M. T.; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 64  Nº 2, Supl.  2016  págs. S543
Autores: Antolin, G. S.; Testillano, M.; Prieto, M.; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 64  Nº 2, Supl.  2016  págs. S538 - S539
Autores: Milara, J.; Outeda-Macias, M.; Aumente-Rubio, M. D.; et al.
Revista: FARMACIA HOSPITALARIA
ISSN 1130-6343  Vol. 39  Nº 1  2015  págs. 29 - 43
Objective: Dual PEGylated interferon-¿ (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Methods: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. Results: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNF¿ (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. Conclusions: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.
Autores: Bilbao, I.; Salcedo, M.; Gómez, M. A.; et al.
Revista: LIVER TRANSPLANTATION
ISSN 1527-6465  Vol. 21  Nº 8  2015  págs. 1056 - 1065
A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m2) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy.
Autores: Salem, R.; Voche, M.; Baker, T.; et al.
Revista: TRANSPLANTATION
ISSN 0041-1337  Vol. 99  Nº 11  2015  págs. 2347 - 2355
Background: Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. Methods: Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. Results: The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. Conclusions: The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.
Autores: Sarobe, Pablo; Merino, J; et al.
Revista: TRANSPLANT IMMUNOLOGY
ISSN 0966-3274  Vol. 33  Nº 2  2015  págs. 110 - 116
Several studies have shown that some liver transplant recipients may tolerate immunosuppression withdrawal. Mechanisms and biomarkers of tolerance are not well known. Methods: Twenty-four LT patients with immunosuppression side-effects underwent progressive immunosuppression withdrawal. Peripheral lymphocyte populations and secretion of cytokines were analyzed at baseline and during withdrawal until tolerance (n = 15) or rejection (n = 9), as well as 3. months after tolerance achievement or rejection resolution (as follow-up). Immunological markers were compared among groups. Results: The percentages of CD3 + CD4 + cells progressively decreased in both groups. CD3 + CD8 + cells gradually increased in tolerant patients. B lymphocytes gradually decreased in tolerant and initially in non-tolerant patients, reverting at rejection. Regulatory T cells progressively increased until rejection in non-tolerants, decreasing to basal levels after renewing immunosuppression; no significant changes were found in tolerant patients. The percentages and absolute counts of natural killer cells significantly increased in both groups, being more evident in tolerant patients. The secretion of several cytokines was higher in non-tolerant patients when rejection was diagnosed. Conclusions: The greater increase of natural killer cells in tolerant patients suggests their potential role in the tolerance phenomenon
Autores: Iñarrairaegui, Mercedes; Páramo, José Antonio; et al.
Revista: LIVER INTERNATIONAL
ISSN 1478-3223  Vol. 35  Nº 5  2015  págs. 1590 - 96
BACKGROUND & AIMS: Radioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liver disease (REILD). Moreover, lobar radioembolization may induce hypertrophy of the non-treated hemiliver most probably by inducing liver regeneration. METHODS: In patients with hepatocellular carcinoma, we prospectively studied serum levels of markers of liver regeneration, oxidative stress, pro-inflammatory pathways, endothelial activation and coagulation parameters over 2 months after radioembolization. RESULTS: Although REILD did not occur among 14 treated patients, a decrease in effective liver blood flow was observed. Radioembolization was followed by a persistent increase in pro-inflammatory (interleukin 6 and 8) and oxidative stress (malondyaldehide) markers, an induction of endothelial injury markers (vW factor and PAI-1) and an activation of the coagulation cascade (factor VIII, PAI-1, D-Dimer) as well as a significant increase in factors related to liver regeneration (FGF-19 and HGF). CONCLUSION: Radioembolization activates liver regeneration, produces oxidative stress, activates inflammatory cytokines and induces endothelial injury with partial activation of the coagulation cascade. These findings may have implicati
Autores: Torre Cisneros, J.; San-Juan, R.; Rosso Fernández, C.; et al.
Revista: CLINICAL INFECTIOUS DISEASES
ISSN 1058-4838  Vol. 60   Nº 11  2015  págs. 1642 - 1650
Autores: D'Avola, Delia; Carmona, Francisco de Asís; Mendez, M.; et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 62  Nº Supl. 2  2015  págs. S344 - S345
Autores: del Pozo, José Luis; Sáez, Elena; et al.
Revista: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN 0066-4804  Vol. 58  Nº 7  2014  págs. 4227 - 4229
Mitochondrial toxicity has been recently suggested to be the underlying mechanism of long-term linezolid-associated toxicity in patients with 16S rRNA genetic polymorphisms. Here, we report for the first time two cases of lactic acidosis due to long-term linezolid exposure in liver transplant recipients who presented an A2706G mitochondrial DNA polymorphism.
Autores: G. Sapisochin; C. Rodrígue de Lópe; M. Gastaca; et al.
Revista: ANNALS OF SURGERY
ISSN 0003-4932  Vol. 259  Nº 5  2014  págs. 944-952
Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.
Autores: Herrero, José Ignacio; Iñarrairaegui, Mercedes; D'Avola, Delia; et al.
Revista: GASTROENTEROLOGIA Y HEPATOLOGIA
ISSN 0210-5705  Vol. 37  Nº 4  2014  págs. 233-239
The FibroScan(®) XL probe has been specifically designed for obese patients to measure liver stiffness by transient elastography, but it has not been well tested in non-obese patients. The aim of this study was to compare the M and XL FibroScan(®) probes in a series of unselected obese (body mass index above 30 kg/m(2)) and non-obese patients with chronic liver disease. Two hundred and fifty-four patients underwent a transient elastography examination with both the M and XL probes. The results obtained with the two probes were compared in the whole series and in obese (n=82) and non-obese (n=167) patients separately. The reliability of the examinations was assessed using the criteria defined by Castéra et al. The proportion of reliable exams was significantly higher when the XL probe was used (83% versus 73%; P=.001). This significance was maintained in the group of obese patients (82% versus 55%; P<.001), but not in the non-obese patients (84% versus 83%). Despite a high correlation between the stiffness values obtained with the two probes (R=.897; P<.001), and a high concordance in the estimation of fibrosis obtained with the two probes (Cronbach's alpha value: 0.932), the liver stiffness values obtained with the XL probe were significantly lower than those obtained with the M probe, both in the whole series (9.5 ± 9.1 kPa versus 11.3 ± 12.6 kPa; P<0.001) and in the obese and non-obese groups. In conclusion, transient elastography with the XL probe allows a higher proportio
Autores: D'Avola, Delia; Carmona, Francisco de Asís; Mendez, M.; et al.
Revista: MOLECULAR THERAPY
ISSN 1525-0016  Vol. 22  Nº Supl.1  2014  págs. S273 - S274
Autores: D'Avola, Delia; Carmona, Francisco de Asís; Mendez, M.; et al.
Revista: HUMAN GENE THERAPY
ISSN 1043-0342  Vol. 25  Nº 11  2014  págs. A45 - A46
Autores: Alegre, Félix; Herrero, José Ignacio; Iñarrairaegui, Mercedes; et al.
Revista: ACTA GASTRO-ENTEROLOGICA BELGICA
ISSN 1784-3227  Vol. 76  Nº 2  2013  págs. 246-50
Patients with heart failure have increased liver stiffness, that appears to be related with the severity of heart failure
Autores: Barbero, R.; Rodríguez, Carlos Manuel; Pérez-Vizcaíno, F.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 8  Nº 1  2013  págs. e52683
Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta-blockers.
Autores: Chopitea, Ana; Iñarrairaegui, Mercedes; et al.
Revista: Hepatology
ISSN 0270-9139  Vol. 57  Nº 3  2013  págs. 1078 - 1087
Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P < 0.0001). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, P = 0.93). Exposure to chemotherapy in the 2-month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2013)
Autores: Sarobe, Pablo; Merino, J; et al.
Revista: LIVER TRANSPLANTATION
ISSN 1527-6465  Vol. 19  Nº 9  2013  págs. 937 - 944
Recipients of liver transplantation (LT) may develop immunological tolerance. Factors predictive of tolerance are not clearly understood. Transplant recipients with normal liver function tests and without active viral hepatitis or autoimmune disease who presented with side effects of immunosuppression or a high risk of de novo malignancies were selected to participate in this prospective study. Twenty-four patients fulfilled the inclusion criteria and, therefore, underwent a gradual reduction of immunosuppression. Tolerance was defined as normal liver function tests after immunosuppression withdrawal. Basal clinical and immunological characteristics, including lymphocyte counts and subpopulations (T, B, natural killer, CD4+, CD8+, and regulatory T cells) and the phytohemagglutinin stimulation index (SI), were compared for tolerant and nontolerant patients. Fifteen of the 24 patients (62.5%) were tolerant at a median of 14 months (interquartile range¿=¿8.5-22.5 months) after complete immunosuppression withdrawal. Tolerant patients had a longer median interval between transplantation and inclusion in the study (156 for tolerant patients versus 71 months for nontolerant patients, P¿=¿0.003) and a lower median SI (7.49 for tolerant patients versus 41.73 for nontolerant patients, P¿=¿0.01). We identified 3 groups of patients with different probabilities of tolerance: in the first group (n¿=¿7 for an interval¿>¿10 years and an SI¿<¿20), 100% reached tolerance; in the second group (n¿=¿10 for an interval¿>¿10 years and an SI¿>¿20 or an interval¿<¿10 years and an SI¿<¿20), 60% reached tolerance; and in the third group (n¿=¿7 for an interval¿<¿10 years and an SI¿>¿20), 29% reached tolerance. In conclusion, a high proportion of select LT recipients can reach tolerance over the long term. Two simple basal variables¿the time from transplantation and the SI¿may help to identify these patients.
Autores: Herrero, José Ignacio; Bastarrika, Gorka; D'Avola, Delia; et al.
Revista: ANNALS OF TRANSPLANTATION
ISSN 1425-9524  Vol. 18  2013  págs. 587 - 592
Background: The prognosis of non-cutaneous malignancies after liver transplantation is dismal, mainly because most cases are diagnosed at advanced stages. In the last decade, studies have shown the potential role of screening for lung cancer with low-radiation dose computed tomography. Material/Methods: Fifty-nine liver transplant recipients with a cumulative dose of smoking greater than 10 pack-years were enrolled in a lung cancer screening program using yearly low-radiation dose computed tomography. Results: Lung cancer was diagnosed in 7 patients (11.8%), 5 of which were in stage Ia at diagnosis. Patients with lung cancer were significantly older (median age 66 vs. 58 years), had a higher cumulative history of smoking, and had emphysema more frequently than patients without cancer. Conclusions: Screening for lung cancer with low-radiation dose computed tomography in liver transplant recipients results in the diagnosis of lung cancer in early stages.
Autores: Rotellar, Fernando; Pardo, Fernando; Benito, Alberto; et al.
Revista: AMERICAN JOURNAL OF TRANSPLANTATION
ISSN 1600-6135  Vol. 13  Nº 12  2013  págs. 3269-3273
The overriding concern in living donor liver transplantation is donor safety. A totally laparoscopic right hepatectomy without middle hepatic vein for adult living donor liver transplantation is presented. The surgical procedure is described in detail, focusing on relevant technical aspects to enhance donor safety, specifically the hanging maneuver and dynamic fluoroscopy-controlled bile duct division.
Autores: Herrero, José Ignacio;
Revista: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
ISSN 0815-9319  Vol. 27  Nº 6  2012  págs. 1011 - 1016
De novo malignancies are frequent complications after liver transplantation. They are one of the leading causes of late death. Some authors have reported promising results following implementation of extensive cancer surveillance programs
Autores: D'Avola, Delia; Bilbao, José Ignacio; et al.
Revista: Transplantation Proceedings
ISSN 0041-1345  Vol. 44  Nº 9  2012  págs. 2603 - 26058
Autores: Berenguer, M.; Charco, R.; Pascasio, J. M.; et al.
Revista: Liver International
ISSN 1478-3223  Vol. 32  Nº 5  2012  págs. 712 - 731
In November 2010, the Spanish Society of Liver Transplantation (Sociedad Espanola de Trasplante Hepatico, SETH) held a consensus conference. One of the topics of debate was liver transplantation in patients with hepatitis C. This document reviews (i) the natural history of post-transplant hepatitis C, (ii) factors associated with post-transplant prognosis in patients with hepatitis C, (iii) the role of immunosuppression in the evolution of recurrent hepatitis C and response to antiviral therapy, (iv) antiviral therapy, both before and after transplantation, (v) follow-up of patients with recurrent hepatitis C and (vi) the role of retransplantation.
Autores: Campistol, Josep M; Cuervas-Mons, Valentin; Manito, Nicolas; et al.
Revista: Transplantation Reviews
ISSN 0955-470X  Vol. 26  Nº 4  2012  págs. 261 - 279
Solid-organ transplant recipients are at increased risk of developing cancer compared with the general population. Tumours can arise de novo, as a recurrence of a preexisting malignancy, or from the donated organ. The ATOS (Aula sobre Trasplantes de Organos Solidos; the Solid-Organ Transplantation Working Group) group, integrated by Spanish transplant experts, meets annually to discuss current advances in the field. In 2011, the 11th edition covered a range of new topics on cancer and transplantation. In this review we have highlighted the new concepts and best practices for managing cancer in the pre-transplant and post-transplant settings that were presented at the ATOS meeting. Immunosuppression plays a major role in oncogenesis in the transplant recipient, both through impaired immunosurveillance and through direct oncogenic activity. It is possible to transplant organs obtained from donors with a history of cancer as long as an effective minimization of malignancy transmission strategy is followed. Tumour-specific wait-periods have been proposed for the increased number of transplantation candidates with a history of malignancy; however, the patient's individual risk of death from organ failure must be taken into consideration. It is important to actively prevent tumour recurrence, especially the recurrence of hepatocellular carcinoma in liver transplant recipients. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients, with long-term intensive screening programs showing a reduced incidence of cancer post-transplantation. Proposed management strategies for post-transplantation malignancies include viral monitoring and prophylaxis to decrease infection-related cancer, immunosuppression modulation with lower doses of calcineurin inhibitors, and addition of or conversion to inhibitors of the mammalian target of rapamycin.
Autores: Gómez-Martín, Carlos; Bustamante, Javier; Castroagudin, Javier F.; et al.
Revista: Liver Transplantation
ISSN 1527-6465  Vol. 18  Nº 1  2012  págs. 45 - 52
There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation. This open, multicenter, retrospective, uncontrolled cohort study was designed to evaluate the safety and preli
Autores: D'Avola, Delia; Iñarrairaegui, Mercedes; et al.
Revista: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY RESEARCH
ISSN 2224-3992  Vol. 1  Nº 6  2012  págs. 111 - 113
Autores: Rotellar, Fernando; Álvarez-Cienfuegos, Francisco Javier; et al.
Revista: Transplantation Proceedings
ISSN 0041-1345  Vol. 44  Nº 6  2012  págs. 1560 - 1561
Autores: Iñarrairaegui, Mercedes; Pardo, Fernando; Bilbao, José Ignacio; et al.
Revista: European Journal of surgical Oncology
ISSN 0748-7983  Vol. 38  Nº 7  2012  págs. 594 - 601
Autores: Herrero, José Ignacio; España, Agustín; D'Avola, Delia; et al.
Revista: Transplantation Proceedings
ISSN 0041-1345  Vol. 44  Nº 6  2012  págs. 1568 - 1570
Autores: Berasain, C; Schmitz, Volker; et al.
Revista: Journal of Hepatology
ISSN 0168-8278  Vol. 55  Nº 4  2011  págs. 828 - 837
Autores: Herrero, José Ignacio; Pardo, Fernando; Rotellar, Fernando; et al.
Revista: Transplantation Proceedings
ISSN 0041-1345  Vol. 43  Nº 3  2011  págs. 690 - 691
Fewer than 25% of potential liver donors became effective donors leading us to conclude that adult living donor liver transplantation has a low applicability
Autores: Herrero, José Ignacio;
Revista: GASTROENTEROLOGIA Y HEPATOLOGIA CONTINUADA
ISSN 1578-1550  Vol. 10  Nº 3  2011  págs. 99 - 102
Autores: Riezu-Boj, José Ignacio; Larrea, Esther; Aldabe, R; et al.
Revista: JOURNAL OF HEPATOLOGY
ISSN 0168-8278  Vol. 54  Nº 3  2011  págs. 422 - 431
Autores: Herrero, José Ignacio; Pardo, Fernando; D'Avola, Delia; et al.
Revista: Liver Transplantation
ISSN 1527-6465  Vol. 17  Nº 4  2011  págs. 402 - 408
Liver transplant recipients have an increased risk of malignancy. Smoking is related to some of the most frequent causes of posttransplant malignancy. The incidence and risk factors for the development of neoplasia related to smoking (head and neck, lung, esophageal, and kidney and urinary tract carcinomas) were studied in 339 liver transplant recipients. Risk factors for the development of smoking-related neoplasia were also studied in 135 patients who had a history of smoking so that it could be determined whether smoking withdrawal was associated with a lower risk of malignancy. After a mean follow-up of 7.5 years, 26 patients were diagnosed with 29 smoking-related malignancies. The 5- and 10-year actuarial rates were 5% and 13%, respectively. In multivariate analysis, smoking and older age were independently associated with a higher risk of malignancy. In the smoker subgroup, the variables related to a higher risk of malignancy were active smoking and older age. In conclusion, smoking withdrawal after liver transplantation may have a protective effect against the development of neoplasia
Autores: D'Avola, Delia; Iñarrairaegui, Mercedes; Pardo, Fernando; et al.
Revista: ANNALS OF SURGICAL ONCOLOGY
ISSN 1068-9265  Vol. 18  Nº 7  2011  págs. 1964 - 1971
Autores: Herrero, José Ignacio;
Revista: Gastroenterologia y Hepatologia
ISSN 0210-5705  Vol. 34  Nº 9  2011  págs. 641 - 659
La constante actualización en el campo del trasplante hepático llevó a la celebración de la III Reunión de consenso de la Sociedad Española de Trasplante Hepático. En ella se debatió acerca de 3 temas actuales y de gran interés clínico: el trasplante en pacientes con cirrosis hepática por virus C, trasplante hepático de donante vivo y la evaluación de la calidad de los injertos hepáticos. También se abordó un tema de gran interés para las unidades de trasplante hepático: la evaluación de su calidad. The constant updating in the field of liver transplant led to the holding of the III Consensus Meeting of the Spanish Liver Transplant Association. Three current topics of great clinical interest were debated during this meeting; transplant in patients with liver cirrhosis due to hepatitis C, live donor liver transplant and the evaluation of the quality of liver grafts. A subject of great interest to Liver Transplant Units was also discussed: the assessment of their quality.
Autores: Herrero, José Ignacio; Pardo, Fernando; Quiroga, Jorge Augusto;
Revista: Liver Transplantation
ISSN 1527-6465  Vol. 17  Nº 8  2011  págs. 988 - 988
Autores: Iñarrairaegui, Mercedes; Rodríguez-Fraile, M; et al.
Revista: International Journal of Radiation Oncology, Biology, Physics
ISSN 0360-3016  Vol. 77  Nº 5  2010  págs. 1441 - 1448
Autores: Sangro, Bruno; Mazzolini Rizzo, G.D.; et al.
Revista: Cancer Gene Therapy (Print)
ISSN 0929-1903  Vol. 17  Nº 12  2010  págs. 837 - 843