M Navasa

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcino, Catalonia, Spain

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Publications (208)1320.23 Total impact

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    ABSTRACT: Background Invasive aspergillosis (IA) has been considered an infrequent complication after renal transplantation. We aimed to evaluate the differences in clinical and epidemiologic characteristics of IA between renal and other types of transplantation.Methods We reviewed all cases of solid organ transplant (SOT) recipients from Hospital Clinic at Barcelona, who had proven and probable IA, according to the EORTC/MSG criteria, between June 2003 and December 2010.ResultsA total of 1762 transplants were performed. From this cohort, 27 cases of IA were diagnosed (1.5%): in 56% (15/27) liver, 33% (9/27) kidney, and 11% (3/27) combined transplant. The median onset time from renal and non-renal transplants to IA was 217 and 10 days, respectively (P < 0.001). There were 6 cases (22%) of late IA (>6 months), all in kidney recipients (P < 0.001). Renal transplant patients with IA more frequently had chronic lung disease (44% vs. 6%) and chronic heart failure (33% vs. 6%); they also had none of the classical risk factors for IA defined for liver transplantation (0% vs. 33%, P = 0.001), and therefore they did not receive antifungal prophylaxis (0% vs. 72%, P = 0.001). In 14/24 patients, serum galactomannan antigen was positive, and this related to higher mortality.Conclusions While classical risk factors described for IA in liver recipients are still valid, IA appears later in renal patients and is commonly associated with co-morbid conditions.
    Transplant Infectious Disease 10/2014; · 1.98 Impact Factor
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    ABSTRACT: Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ+ in CD4+CD69+ and in CD8+CD69+ and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2+ in CD8+CD69+ also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.
    Clinical Immunology 10/2014; · 3.99 Impact Factor
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    ABSTRACT: The incidence of candidemia by non-Candida albicans Candida species has been progressively increasing in recent years. The use of fluconazole as antifungal prophylaxis has been described as a risk factor for the development of infections by fluconazole resistant Candida strains. We report a case of Candida norvegensis bloodstream infection in a liver transplant recipient. A 61-year-old man, who received a third liver allograft that became worse with an ischemic cholangiopathy and recurrent episodes of cholangitis, was admitted to our hospital due to the development of intra-abdominal abscesses. He received multiple antibiotic schemes, and after 3 months he was discharged, maintaining parenteral antibiotic at home. While he was on fluconazole prophylaxis, a breakthrough candidemia by C. norvegensis occurred. In vitro susceptibilities of the isolate to several antifungal agents were as follows: amphotericin B MIC 0.5mg/l, flucytosine 64mg/l, fluconazole 64mg/l, itraconazole 4mg/l, voriconazole 0.75mg/l, and caspofungin 0.047mg/l. He was treated with anidulafungin with resolution of candidemia. The use of fluconazole for antifungal prophylaxis may lead to the emergence of fluconazole-resistant Candida infections, with C. norvegensis being a possible emerging pathogen in organ transplant recipients.
    Revista iberoamericana de micologia. 05/2014;
  • Journal of Hepatology 04/2014; 60(1):S410. · 10.40 Impact Factor
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    ABSTRACT: The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C-infected and 48 non-hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p < 0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM < 8.7 kPa (p < 0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p < 0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.
    American Journal of Transplantation 01/2014; · 6.19 Impact Factor
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    ABSTRACT: Antecedentes En los últimos años ha aumentado la incidencia de candidemia causada por especies del género Candida distintas de Candida albicans. Se ha descrito el uso de profilaxis antifúngica con fluconazol como factor de riesgo para el desarrollo de infecciones por cepas de Candida resistentes a este antifúngico. Se describe un caso de fungemia por Candida norvegensis en un receptor de un trasplante hepático. Caso clínico Un varón de 61 años, receptor de un tercer trasplante hepático que se complica con una colangiopatía isquémica y episodios de colangitis de repetición, ingresó en nuestro hospital por presentar abscesos intraabdominales. Recibió múltiples esquemas antibióticos y, tras tres meses de ingreso, se dio de alta manteniendo un tratamiento antibiótico parenteral en domicilio. Mientras recibía profilaxis con fluconazol, desarrolló una candidemia de brecha por C. norvegensis. Los valores de CMI in vitro del aislamiento para algunos antifúngicos fueron los siguientes: anfotericina B 0,5 mg/l, flucitosina 64 mg/l, fluconazol 64 mg/l, itraconazol 4 mg/l, voriconazol 0,75 mg/L y caspofungina 0,047 mg/l. El paciente recibió tratamiento con anidulafungina con resolución de la candidemia. Conclusiones El uso del fluconazol como profilaxis antifúngica puede conllevar la aparición de infecciones por especies de Candida resistentes a este antifúngico, siendo C. norvegensis un posible patógeno emergente en pacientes receptores de un órgano sólido.
    Revista Iberoamericana de Micología 01/2014; · 0.97 Impact Factor
  • Journal of Hepatology 04/2013; 58:S70. · 10.40 Impact Factor
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    ABSTRACT: Opportunistic pulmonary infections (OPI) represent common life-threatening complications after solid organ transplantation. Our objective was to describe pulmonary infections caused by opportunistic pathogens in solid-organ transplant patients. We analyzed all adult solid organ recipients (liver, heart, kidney, and pancreas) between July 2003 and June 2010, reporting all episodes of pulmonary opportunistic infection. During the study period, 1656 solid organ transplants were performed and 188 opportunistic infections were diagnosed in 163 patients (incidence 10%). In 40 cases, the site of infection was the lung (21%) with 57.5% occurring between the first and sixth month posttransplantation. The most frequently isolated microorganism was Aspergillus spp (n = 25, 63%), followed by Pneumocystis jirovecii (n = 6 cs, 15%). Twenty-five patients with an opportunistic pulmonary infections died during the follow-up including, 16 related to the infection (40%). The causative organism responsible for the highest mortality was Aspergillus spp (n = 12; 48%). Twenty-one patients with an opportunistic nonrespiratory infection died, five of them related to it (4%). Opportunistic pulmonary infection was associated with an increased mortality rate (P < .001). There was a trend toward a higher mortality among patients who developed OPI during the first 6 months after transplantation. Opportunistic pulmonary infections after solid organ transplantation are not infrequent. The period of risk for developing this infectious complications goes beyond the first 6 months posttransplantation. Mortality due to these infections was high in comparison to that of opportunistic nonrespiratory infections. It is important to keep a high index of suspicion for infectious complications during all posttransplant periods, as this is the first step toward a rapid diagnosis and adequate treatment.
    Transplantation Proceedings 11/2012; 44(9):2673-5. · 0.95 Impact Factor
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    ABSTRACT: Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.
    American Journal of Transplantation 09/2012; · 6.19 Impact Factor
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    ABSTRACT: Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.
    American Journal of Transplantation 11/2011; 12(1):162-70. · 6.19 Impact Factor
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    X Forns, M Navasa
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    ABSTRACT: Prospective studies analyzing the potential influence of cyclosporine A versus tacrolimus following liver transplant for hepatitis C virus on the new anti‐viral protease and polymerase inhibitors might help address the perennial debate of the best calcineurin inhibitor for this indication. See article by Irish et al on page 1676.
    American Journal of Transplantation 08/2011; 11(8):1559-60. · 6.19 Impact Factor
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    ABSTRACT: Despite recent advances in prevention and treatment, cytomegalovirus (CMV) is still a major complication in transplant patients. This study sought to analyze the incidence of CMV disease and its impact on patient and graft survival. Between June 2003 and December 2009, we included all kidney, liver, heart, and double transplant patients who underwent solid organ transplantation. They had 1-year posttransplant follow-up. Among the 1427 patients who received kidney (n = 661), liver (n = 494), heart (n = 89), or double (n = 183) transplants, 103 (7.2%) displayed CMV disease. The incidence by type of transplant was: heart (n = 17, 19%), liver (n = 35, 7%), kidney (n = 41, 6.2%), or double transplant (n = 10, 5.5%; P < .001). In 59% of cases, the infection developed during the first 3 months after transplantation. CMV infections ranged from viral syndrome (n = 47, 45%) to tissue-invasive disease (n = 56, 55%), including 38% with gastrointestinal involvement. Relapsing episodes occurred in 12 patients (11%). Discordant donor/recipient CMV serology was present in 151 patients (donor positive/receptor negative), including 34 (22.5%) who developed primary CMV disease (P < .001). Coinfections mostly bacterial, were diagnosed in 38% of patients. An acute rejection episode was present in 31% of patients with CMV disease compared to 20% without this complication (P = .017). Crude mortality was significantly higher among patients with CMV disease (n = 18 patients [18%] vs 92 patients [7%]; P < .001). Our data confirmed that CMV disease was associated with worse transplant outcomes, with higher incidences of acute rejection episodes and mortality.
    Transplantation Proceedings 07/2011; 43(6):2145-8. · 0.95 Impact Factor
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    ABSTRACT: Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the first 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identified. Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio [HR] [per year] 1.0; 95% confidence interval [CI]: 1.0-1,0), female gender (HR 1.7; 95%CI: 1.1-2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1-3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7-6.1), early CMV disease (HR 2.2; 95%CI 1.2-4.1), and early bacterial infection (HR 2.5; 95%CI 1.6-3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMV disease (HR 6.5; 95%CI: 1.7-24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1-1.0). Cox model selected anti-HCV positive serostatus (adjusted HR [aHR] 2.67; 95%CI: 1.27-5.59), age (aHR [per year] 1.06; 95%CI: 1.02-1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90-21.33) as independent factors for mortality. LI did not constitute an uncommon complication in our cohort, and patients at risk may benefit from close clinical monitoring.
    Transplant Infectious Disease 04/2011; 13(6):598-607. · 1.98 Impact Factor
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    ABSTRACT: IL28B gene polymorphisms are associated with the response to antiviral therapy in hepatitis C patients. We investigated the influence of IL28B polymorphisms on the response to therapy before and after liver transplantation (LT). Genotyping of SNPs rs8099917 and rs12979860 was performed in 128 HCV-infected liver transplant recipients and in their donors; all patients underwent antiviral treatment after LT. The prevalence of genotypes rs12979860CC and rs8099917TT was higher in donors than in recipients (50% vs.19%, p < 0.001 and 67% vs. 38%, p < 0.001, respectively). Response to antiviral therapy was significantly higher for recipient genotype rs12979860CC as compared to rs12979860CT/TT both before (100% vs. 48% p = 0.013) and after LT (59% vs. 25% p = 0.002). The figures were almost identical for SNP rs8099917. Sustained virological response after LT was particularly high in patients with favorable recipient and donor genotypes (p < 0.01 for both SNPs). In a subgroup of 34 patients treated while awaiting LT, a favorable donor IL28B genotype was associated with an improved virological response after LT. Our results support a major role of recipient IL28B genotype in the response to antiviral treatment for hepatitis C recurrence. Interestingly, donor genotype also seems to influence the response pattern, especially in recipients who have a favorable IL28B genotype.
    American Journal of Transplantation 04/2011; 11(5):1051-7. · 6.19 Impact Factor
  • Journal of Hepatology 03/2011; 54. · 10.40 Impact Factor
  • Journal of Hepatology 03/2011; 54. · 10.40 Impact Factor
  • Journal of Hepatology 03/2011; 54. · 10.40 Impact Factor
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    ABSTRACT: Neutralizing antibody (nAb) activity during the course of natural infection is believed to be crucial to combating virus propagation. The aim of this study was to measure the impact of nAb response on HCV early kinetics and genetic evolution in the liver transplantation (LT) setting. A cohort of 28 patients undergoing LT for HCV-related cirrhosis was included in the study. Viral load, nAb titers and hypervariable region 1 (HVR1) sequences were determined in serum samples obtained before and at different time points after LT. Serum nAb titers were assessed using HCV pseudoparticles (HCVpp). HVR1 sequences were obtained by direct sequencing. Patients were classified according to viral kinetic patterns (plateau or increasing), during the first week after LT. All patients demonstrated high titers of nAbs before LT, although this was not associated with early kinetic patterns or HVR1 evolution during the first week after LT. We found that in patients with plateau HCV early kinetics, the virus required adaptive mutations, while in those with increasing viral loads, the HVR1 region remained largely conserved (p = 0.015). These data suggest that HCV adaptation via selection of the best-fitted variants may account for early viral kinetics following LT.
    American Journal of Transplantation 03/2011; 11(4):767-74. · 6.19 Impact Factor
  • Journal of Hepatology 03/2011; 54. · 10.40 Impact Factor
  • Journal of Hepatology 03/2011; 54. · 10.40 Impact Factor

Publication Stats

6k Citations
1,320.23 Total Impact Points

Institutions

  • 2011–2014
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
  • 1993–2014
    • Hospital Clínic de Barcelona
      • • Servicio de Hepatología
      • • Servicio de Reumatología
      Barcino, Catalonia, Spain
  • 1987–2011
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2005
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
  • 1999–2004
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2001
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 1997
    • Hospital Universitari Germans Trias i Pujol
      Badalona, Catalonia, Spain