Victoria Aguilera

Hospital Universitari i Politècnic la Fe, Valenza, Valencia, Spain

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Publications (72)141.76 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the results of the treatment with pegylated interferon and ribavirin for recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients.
    Journal of hepatology. 08/2014;
  • Carmen Vinaixa, Victoria Aguilera, Marina Berenguer
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    ABSTRACT: Recent approval of new protease inhibitors (boceprevir and telaprevir) for the treatment of chronic hepatitis C, genotype 1, has meant a significant increase in the sustained viral response both in naive and previously treated patients. However, such efficacy increase has been accompanied by an increase in adverse events, sometimes serious, and new practical issues including different approaches to stop treatment and drug interactions that recommend a close follow-up of patients. The efficacy and safety of triple therapy in special populations such as cirrhotic and transplanted patients is less known and has some particulars, meaning that its administration requires an exhaustive monitoring.
    Medicina Clínica 11/2013; 141(10):447–452. · 1.40 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) is associated with renal complications. We aimed to determine whether sustained viral response (SVR) is associated with improvement in renal function in HCV-treated liver transplant (LT) recipients. Methods: Changes in renal function were compared 1, 3 and 5 years post-therapy as a function of pre-treatment stage of chronic kidney disease (CKD). In addition, variables associated with renal dysfunction (RD, MDRD-4 ≤ 60 mL/min/1.73 m(2) ) at last follow-up were evaluated in all treated LT patients with a minimum follow up of at least one year since end-of-treatment (n=175). Results: Of 99 patients with pre-treatment CKD stage 2 (MDRD-4 60 - 90 mL/min/1.73 m(2) ), improvement in renal function was observed in SVR patients more frequently than in non-responders. Median pre-treatment, 1, 3 and 5 years post-treatment MDRD-4 values were 71.8, 70,4, 79.4 and 82.1 in SVRs vs 76.2, 72.2, 73.9 and 66.1 in NRs (p=0.17, 0.61, 0.15 and 0.005, respectively). The median changes in MDRD-4 from pre-treatment to 1, 3 and 5 years post-treatment were -0.5, 4.5 and 9.4 in SVR vs -1, -0.3 and -1.5 in NR (p=0.61, 0.06 and 0.004, respectively). RD was present in 54 out of the 175 (31%) patients at last follow up, at a median of 3.8 years since end of therapy (range: 1-9 years). Follow up did not differ between SVR and NR. RD was present at last follow-up in 19% of SVR vs 40% of NR (p=.002). In the multivariate analysis, RD (MDRD-4 ≤ 60 mL/minute/1.73 m(2) ) at last follow up was associated with non-response (RR: 3.8, 95% CI: 1.3-11.23; p=.014), end-of-treatment MDRD-4 (RR: 1.022, 95% CI: 1.001-1.04; p=.044) and female gender (RR: 5.6; 95% CI: 1.84-17.5; p=.002). Conclusions: SVR leads to improved renal function in HCV-infected LT recipients with pre-treatment stage 2 CKD This improvement is not immediate following therapy. Liver Transpl , 2013. © 2013 AASLD.
    Liver Transplantation 09/2013; · 3.94 Impact Factor
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    ABSTRACT: There are few studies focusing on long-term complications in liver transplant (LT) recipients. The aim of this study was to define the outcome of LT recipients having survived at least 10 years from LT. Of 323 adult LT done between 1991 and 1997, the 167(52%) alive >10 years post-LT (baseline time) formed the study population. Long-term outcome measures included the following: immunosuppression, metabolic complications [obesity, arterial hypertension (AH), diabetes, dislypidemia], cardiovascular events (CVE), chronic renal dysfunction-CRD, and de novo tumors. Median age at LT was 50 years. Most common indication was postnecrotic cirrhosis (89%), mostly because of HCV (46%). At study-baseline (10 years post-LT), 29% were obese and AH, diabetes, dislypidemia, and CRD were present in 75%, 30%, 42%, and 36%, respectively. In most cases, these complications were already present 1 year post-LT; less than one quarter developed them onward. The 6 year cumulative survival since baseline reached 84% (n = 24 deaths), with most deaths related to recurrent graft diseases (mostly HCV) followed by de novo tumors or CVE. 1, 3, 5 and 10 years cumulative rates of CVE and de novo tumors since baseline were 2%, 5%, 10% and 17%, and 1%, 3%, 6% and 13%, respectively. Chronic renal impairment was independently associated with survival and development of CVE since baseline. The medium-term survival of 'long-term survivors', i.e. patients alive 10 years after LT is good, but metabolic complications and CRD are common and continue to increase afterwards. Cardiovascular events and de novo tumors increase gradually over time and represent a major cause of late mortality.
    Transplant International 04/2013; · 3.16 Impact Factor
  • Carmen Vinaixa, Victoria Aguilera, Marina Berenguer
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    ABSTRACT: Recent approval of new protease inhibitors (boceprevir and telaprevir) for the treatment of chronic hepatitis C, genotype 1, has meant a significant increase in the sustained viral response both in naive and previously treated patients. However, such efficacy increase has been accompanied by an increase in adverse events, sometimes serious, and new practical issues including different approaches to stop treatment and drug interactions that recommend a close follow-up of patients. The efficacy and safety of triple therapy in special populations such as cirrhotic and transplanted patients is less known and has some particulars, meaning that its administration requires an exhaustive monitoring.
    Medicina Clínica 04/2013; · 1.40 Impact Factor
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    ABSTRACT: BACKGROUND: Chronic renal impairment is an emerging problem in the management of patients after liver transplantation (LT). METHODS: We prospectively analyzed predictors of chronic kidney disease (CKD) after LT in 179 patients followed for a median of 63 months. Diagnosis of CKD was based on an estimated glomerular filtration rate (GFR) of less than 60 mL/min according to the current position statement from the Kidney Disease Improving Global Outcome. Pretransplantation risk factors were evaluated. A Cox regression analysis, with time-dependent variables evaluated during follow-up, was applied to realize a prognostic model for CKD, and a prognostic index was also calculated. The validity of the model was tested in 149 independent LT patients with a median follow-up of 46 months. RESULTS: The cumulative incidence of CKD was 45% at 5 years after LT. Estimated GFR at LT was the only pretransplantation independent risk factor (beta, 0.33; standard error (beta), 0.07; 95% confidence interval, 0.95-0.98). Development of arterial hypertension (hazards ratio [HR], 1.83), episodes of severe infection (HR, 2.15), and estimated GFR (HR, 0.89) after LT were identified as independent prognostic factors at the Cox regression time-dependent analysis. The model was able to identify the patients at higher risk for the development of CKD in the validation set. CONCLUSIONS: Lower renal function at transplantation is associated with a higher risk of CKD after transplantation. A predictive model based on the variation of posttransplantation variables during the course of follow-up can help the clinicians to estimate the probability of CKD in the next 12 months.
    Transplantation 03/2013; · 3.78 Impact Factor
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    ABSTRACT: Introduction. Combined liver-kidney transplantation (LKT) is the best therapeutic option for patients with end-stage liver and kidney disease. Objectives. To analyze baseline characteristics and clinical outcome of LKT compared to isolated liver transplantation (LT). Material and methods. The study included 16 LKT performed between 1998 and 2006 and 32 LT matched by age, sex, date and indication for transplantation. Demographic, pretransplant, post-transplant and survival variables were analyzed. Results. As planned by the study design, mean age, distribution by sex and indication for LT were similar between groups. The most common indication for LT was HCV- and/or alcohol-induced cirrhosis. The most common indication for KT was renal failure, in most cases secondary to glomerulonephritis. Twelve patients (69%) were on dialysis before LKT. Hepatocellular carcinoma and diabetes mellitus pre-transplantation were similar between groups. However pretransplant arterial hypertension (AHT) was higher in LKT than LT (50% vs. 19%; p = 0.02). In the post-transplant: reoperation due to bleeding, bacterial infections, liver rejection, AHT and median creatinine levels at 1st and 3rd years were similar in LKT and LT. In contrast, early post-transplant dialysis was higher in LKT than LT (31% vs. 3%; p = 0.01). Survival rates at 1st, 3rd, 5th and 7th years were similar in both groups (87.5%, 74%, 74% and 66% vs. 81%, 75%, 75% and 75% in LT and LKT, respectively). Conclusions. LKT is an effective therapeutic option in patients with end-stage liver and kidney disease. Most early and late complications and long-term survival are similar to those observed with LT.
    Annals of hepatology: official journal of the Mexican Association of Hepatology 03/2013; 12(2):274-81. · 1.67 Impact Factor
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    ABSTRACT: Recurrence of hepatitis C virus (HCV) infection following liver transplantation is a major source of morbidity and mortality. The natural history of hepatitis C in the transplant setting is shortened. Overall, one third of HCV-infected recipients have developed allograft cirrhosis due to HCV recurrence by the 5(th)-7(th) year post-transplantation. The most significant variables which determine disease progression are the use of organs from old donors, the use of an inadequate immunosuppression (too low, inducing treatment rejection episodes, too potent or too rapidly changing), and the presence of comorbid conditions that also impact the quality of the graft (biliary complications, metabolic syndrome). The only factor consistently shown to modify the natural history of recurrent disease is antiviral therapy. A sustained viral response, achieved by one third of those treated with dual therapy, is associated with improved histology, reduced liver-related complications and increased survival. Variables associated with enhanced viral response with dual therapy include an adequate genetic background (IL28B C/C of both donor and recipient), good treatment adherence (full doses of ribavirin, treatment duration), lack of graft cirrhosis at baseline, and viral genotype non-1. Data with triple therapy are encouraging. Response rates of about 60% at end-of-therapy have been described. Drug-drug interactions with calcineurin inhibitors are present but easily manageable with strict trough levels monitoring. Side effects are frequent and severe, particularly anemia, infections and acute renal insufficiency. In the future new oral antivirals will likely prevent viral reinfection. In this review, we will cover the most significant but also controversial aspects regarding recurrent HCV infection, including the natural history, retransplantation, antiviral therapy, and outcome in HIV-HCV patients.
    Annals of Gastroenterology 01/2013; 26(4):304-313.
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    ABSTRACT: AbstractA sustained virological response (SVR) is achieved by 30% of naive liver transplantation (LT) recipients treated with pegylated interferon (PEG‐IFN) and ribavirin (RBV). Almost no data are available about retreatment. The aim of this study was to assess the efficacy, tolerability, and SVR predictors of retreatment. Data were collected from 4 centers on the retreatment of prior nonresponders to standard therapy or PEG‐IFN (with or without RBV) and relapsers. Seventy‐nine of 301 treatment‐experienced LT patients (26%), who had a median age of 59 years (range = 35‐77 years) and were mostly male (72%) and infected with genotype 1 (87%), were retreated with PEG‐IFN and RBV at a median of 6.9 years after LT. During the first course of therapy, 35% were treated with interferon, 49% received tacrolimus, 52% received steroids, and 49.5% were relapsers. Retreatment was started at a median of 1.9 years (range = 45 days to 8.2 years) after the end of the first course. The proportion of patients with cirrhosis increased from 10% to 37% (P P = 0.03), growth factors [erythropoietin (P P = 0.048)], and transfusions (P = 0.03) were used more frequently, and the treatment duration was longer (P = 0.03). An end‐of‐treatment response was achieved in 61%, whereas SVR, which was associated with improved survival, occurred in 28 (35%). The variables predicting SVR were age (P = 0.04), disease severity [fibrosis (50% with F0‐F2 versus 26% with F3‐4), P = 0.03; bilirubin, P = 0.006; platelet count, P = 0.03], adherence, and viral kinetics. None of the patients without an early virological response achieved SVR. There was a trend of prior relapsers achieving higher SVR rates than prior nonresponders. In conclusion, SVR, which was achieved by approximately one‐third of the retreated patients, can be predicted with the same variables used for naive LT recipients (age, disease severity, adherence, and viral kinetics) and is associated with enhanced survival. Liver Transpl 19:69–77, 2013. © 2012 AASLD.
    Liver Transplantation 01/2013; 19(1). · 3.94 Impact Factor
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    ABSTRACT: Increased blood pressure (BP) is common after liver transplantation. However, there is scarce information on its control. In this prospective, cross-sectional, multicenter study, we determined BP according to the recommended international standards in 921 liver transplant patients during one routine outpatient visit to assess their grade of control of BP. At the time of the study, 490 patients had been previously diagnosed with arterial hypertension and were receiving antihypertensive treatment, and 431 were not previously diagnosed as hypertensive. In the hypertensive group, arterial hypertension was uncontrolled (BP >140/90 mm Hg [>130/80 in diabetics]) in 158 (32%) patients and controlled in 332 (68%) patients. In a multivariate analysis, only diabetes was identified as a significant predictor of uncontrolled hypertension. Among patients not previously diagnosed as hypertensive, BP was increased in 106 (25%) and normal in 325 (75%). On multivariate analysis, the only variable independently associated with increased BP in this group was metabolic syndrome. BP is not adequately controlled in a noticeable percentage of liver transplant patients, especially in subjects with diabetes or metabolic syndrome.
    Transplantation 03/2012; 93(10):1031-7. · 3.78 Impact Factor
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    ABSTRACT: Predictors of sustained virological response (SVR) to antiviral therapy post-liver transplantation (LT) for chronic hepatitis C are needed. In non-transplanted patients, viral kinetics can predict SVR. To determine the early viral kinetics in LT recipients with different immunosuppression (tacrolimus - Tac- vs. cyclosporine - CsA-) during treatment with peg-IFN+RBV. Prospective pilot study in HCV-1b infected patients: (LT CsA n=8; Tac n=8; non-LT n=4), treated with IFN α-2a vs. α-2b (180 μg or 1.5 μg/kg, respectively) once weekly plus weight-based RBV. Median CsA or Tac baseline trough levels were 141 and 7.70 ng/mL, respectively. HCV-RNA was quantified before treatment and after 3, 6, 12h; days 1-6; and weeks 4, 12, 24, 48 and 78 (follow-up). Different kinetics were observed: early viral load declines with shoulder phase (n=12), delayed monophasic without first phase (n=5, all CsA), and biphasic (n=1) or flat (n=1), without influence of IL28B rs12979860 donor/recipient alleles. In LT, median declines (log(10)UI/mL) at week 4 were -3.62 and -1.49 for Tac vs. CsA; and -2.10 vs.-1.50 for IFN α-2a vs. α-2b (NS), with a trend for faster declines in Tac patients. Generalized additive models suggested a cut-off for predicting response in LT patients of 30 days for Tac, but beyond day 40 for CsA. In LT, the viral kinetics during peg-IFN+RBV treatment is delayed. HCV-RNA at 48 h. may not be predictive of response, and CsA-immunosupressed patients with delayed monophasic declines may potentially achieve ETVR and SVR despite unfavourable or absent early viral load declines.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2012; 53(3):231-8. · 3.12 Impact Factor
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    ABSTRACT: In a previous study, advanced fibrosis was associated with worsening efficacy of antiviral therapy in HCV-transplant patients. We aimed at assessing whether changes in treatment policy, that is starting therapy at lesser stages of fibrosis, have resulted in improved efficacy. Efficacy (rapid, early, end-of-treatment, and sustained viral response (SVR)) and tolerability (peginterferon (pIFN)/ribavirin (RBV) doses, premature discontinuation, dose reductions, anemia, growth factors, transfusions) were compared between two non-contemporaneous cohorts of post-LT naïve patients treated with pIFN-RBV: Group 1 (n=44), a historical cohort of patients treated during the period 2005-2007 and Group 2 (n=70), patients treated more recently (2007-2010), where treatment was started once there was evidence of fibrosis. SVR increased from 25% to 54% (p=0.002) due to a reduction in relapse rate. Comparing both cohorts, a decrease in the number of cirrhotic patients together with an increase in platelet count was observed in recent years. Additional non-intentional changes included: (i) an increase of patients treated under cyclosporine immunosuppression, (ii) treatment-related factors with an increase in patients treated with initial full pIFN and RBV doses, who developed anemia and hence required dose modifications and erythropoietin. Baseline factors associated with SVR were younger donor age, lack of cirrhosis or severe necroinflammation and the use of RBV at full doses at initiation while on-treatment variables were adherence and viral kinetics. Treatment in the absence of cirrhosis is associated with higher SVR warranting strict disease progression monitoring. A more aggressive approach, particularly regarding RBV dosage, is also associated with improved efficacy. Further studies are required to assess whether switching to cyclosporine will result in improved SVR.
    Journal of Hepatology 02/2012; 56(6):1310-6. · 9.86 Impact Factor
  • A Rubín, V Aguilera, M Berenguer
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    ABSTRACT: Hepatitis C virus (HCV)-related end-stage cirrhosis with/without hepatocellular carcinoma is the primary indication for liver transplantation in many countries. Unfortunately, HCV is not eliminated by transplantation and graft re-infection is the rule, resulting in HCV-related graft disease. The natural history of recurrent hepatitis is variable; overall, progression to cirrhosis occurs in 20-30% and allograft failure in 10% after 5-10 years from transplantation. The use of poor quality organs, particularly from old donors, has a significant negative impact on disease severity and transplant outcome. In contrast, antiviral therapy, particularly if it results in permanent eradication of the virus, is associated with improved histology, reduced rate of graft decompensation and enhanced outcome. Disease monitoring, through protocol liver biopsies and new non-invasive tools, is essential to select patients at need of antiviral therapy. Peginterferon with ribavirin, used similarly to what is done in the non-transplant setting, is currently the treatment of choice; sustained viral response is achieved in about 35% of cases. Side effects, particularly anemia, are extremely frequent and sometimes severe (rejection, de novo autoimmune hepatitis). Retransplantation (RT) is the last option for the small subset of patients with allograft failure due to HCV recurrence who fulfil minimum criteria based on RT survival models.
    Gastroentérologie Clinique et Biologique 09/2011; 35(12):805-12. · 0.80 Impact Factor
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    ABSTRACT: In the immunocompetent setting, antiviral therapy-related anemia has recently been shown to be associated with a sustained virological response (SVR). Our goal was to assess whether this is also true for liver transplantation (LT). We included 160 LT patients with recurrent hepatitis C virus (HCV) who were treated with pegylated interferon and ribavirin (RBV) between 2002 and 2010; 76% of the patients were men, the median age of the patients was 56 years (range = 33-75 years), 63% had advanced fibrosis, and 86% were infected with HCV genotype 1a or 1b. The baseline immunosuppression was tacrolimus in 56% of the patients. Mycophenolate mofetil (MMF) was used in 15%. Anemia was defined as a hemoglobin (Hb) level < 10 g/dL. Significant anemia was present when the Hb decline was >5 g/dL. Anemia and significant anemia developed in 67% and 41% of the patients, respectively. Erythropoietin was used in 60%. Factors independently associated with significant anemia included low estimated creatinine clearance [relative risk (RR) = 0.951, 95% confidence interval (CI) = 0.925-0.978, P = 0.0001], a longer time from LT to therapy (RR = 1.001, 95% CI = 1.000-1.001, P = 0.002), high baseline viremia (RR = 3.2, 95% CI = 1.3-8.1, P = 0.01), cyclosporine A (CSA)-based immunosuppression (RR: 3.472, 95% CI: 1.386-8.695; P = 0.008), and the use of MMF (RR: 5.346, 95% CI: 1.398-20.447; P = 0.014). An SVR occurred in 43% of the patients; the factors associated with an SVR included baseline variables (younger recipient age, younger donor age, infections with non-1 HCV genotypes, body mass index, and mild fibrosis) and on-treatment factors related to adherence or viral kinetics. Anemia resulted in RBV dose reductions but was not associated with the virological response at any time. In conclusion, anemia is a very frequent complication in LT patients during antiviral therapy and is associated with increased RBV dose reduction but not with an SVR. Predictors of anemia include MMF or CSA immunosuppression, high viremia, and renal insufficiency.
    Liver Transplantation 07/2011; 17(11):1318-27. · 3.94 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
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    ABSTRACT: There is a paucity of good studies evaluating the impact of calcineurin inhibitors on posttransplantation outcome in hepatitis C virus (HCV)-infected liver transplant (LT) recipients. We sought to determine whether there are differences on posttransplantation survival and histologic recurrence in HCV-LT recipients based on initial immunosuppression (IS) by conducting a prospective study comparing tacrolimus (Tac) versus cyclosporine-based IS in patients undergoing LT between 2001 and 2007. Protocol liver biopsies were performed. Baseline characteristics (demographics, liver function at LT, genotype distribution, donor, surgery, and IS except for the type of calcineurin inhibitor) did not differ between groups. Severe disease (defined as bridging fibrosis, cirrhosis, cholestatic hepatitis, or allograft loss or death because of recurrent disease in the first year) was present in 67 of 253 (26.5%) and was equally distributed in the CsA and Tac groups (27% vs. 26%; P=0.68). Two thirds of protocol biopsies performed at 1 year showed some fibrosis without differences between CsA and Tac groups (75% vs. 70%). Advanced fibrosis (bridging fibrosis and cirrhosis) was diagnosed in 30% CsA and 24.5% Tac patients (P=NS). No differences in survival at 1 and 7 years were observed (83% and 67% vs. 78% and 64%, respectively, P=0.4). In summary, in patients undergoing LT for HCV-related liver disease, posttransplantation outcome is not related to the calcineurin inhibitor used.
    Transplantation 11/2010; 90(11):1204-9. · 3.78 Impact Factor
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    ABSTRACT: Liver retransplantation (LrT) is the only therapeutic option for irreversible failure of a hepatic graft and accounts for 2.9%-24.0% of all liver transplantations (LT). It is technically difficult and has a high level of immediate morbidity and a lower survival than primary LT. Our aim was to determine the rate of LrT and its indications, morbidity, post-operative mortality and actuarial survival in the retransplanted patient. A historical cohort study of 1181 patients transplanted between 1991 and 2006. Of the 1260 LT performed, 79 were LrT. At the time of the first LT there were no differences between those patients and those that did not require an LrT. The LrT rate was 6.3% and the most frequent causes were: hepatic artery thrombosis (31.6%), recurrence of cirrhosis due the HVC (30.4%) and primary graft (21.5%). The ischemia times, perfusion syndrome and hepatic congestion were no different between the primary LT and the LrT. On the other hand, red cell transfusions were higher in LrT (6.3+/-4.9 vs. 3.5+/-3.0 units, P<0.001). The post-operative morbidity and morbidity (up to 30 days after the LT) was higher in retransplanted patients (68.4% vs. 57.0%, P=0.04 and 25.3% vs. 10.9%, P<0.001; respectively). The actuarial survival at 1 and 5 years was 83% and 69% in those without LrT, 71% and 61% in early LrT and 64% and 34% in delayed LrT (P<0.001). Despite the increased morbidity and mortality of LrT, it appears that this treatment alternative is still valid in those patients with an early loss of the liver graft. On the other hand, when the graft loss is delayed, it needs to be defined, what would be the minimum acceptable results to indicate LrT and which patients could benefit from this treatment.
    Cirugía Española 06/2010; 87(6):356-63. · 0.87 Impact Factor

Publication Stats

796 Citations
141.76 Total Impact Points

Institutions

  • 2001–2014
    • Hospital Universitari i Politècnic la Fe
      • HepatoGastroenterology Service
      Valenza, Valencia, Spain
  • 2013
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
  • 2011
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2010
    • University of Concepción
      • Facultad de Medicina
      Concepción, Region del Biobio, Chile
  • 2006
    • Hospital la Magdalena
      Castellón, Valencia, Spain
  • 2000
    • Colegio Oficial de Médicos de Valencia
      Valenza, Valencia, Spain