367 results on '"Cuervas‐Mons, V"'
Search Results
102. EVIDENCE THAT TEMPORARY COMPLETE OCCLUSION OF SPLENIC VESSELS PREVENTS MASSIVE EMBOLIZATION AND SUDDEN DEATH ASSOCIATED WITH INTRASPLENIC HEPATOCELLULAR TRANSPLANTATION
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NIETO, J. A., primary, ESCANDON, J., additional, BETANCOR, c., additional, RAMOS, J., additional, CANTON, T., additional, and CUERVAS-MONS, v., additional
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- 1989
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103. Effect of colistin on reduction of biliary flow induced by endotoxin ofE. coli
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Escart�n, P., primary, Rodriguez-Montes, J. A., additional, Cuervas-Mons, V., additional, Rossi, I., additional, Alvarez-Cienfuegos, J., additional, Maganto, P., additional, and Castillo-Olivares, J. L., additional
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- 1982
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104. TIME-RELATED EFFICACY OF LIVER CELL ISOGRAFTS IN FULMINANT HEPATIC FAILURE
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CUERVAS-MONS, V., primary, CIENFUEGOS, J. A., additional, MAGANTO, P., additional, GOLITSIN, A., additional, EROLES, G., additional, CASTILLO-OLIVARES, J., additional, and SEGOVIA DE ARANA, J. M., additional
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- 1984
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105. TIMERELATED EFFICACY OF LIVER CELL ISOGRAFTS IN FULMINANT HEPATIC FAILURE
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CUERVAS-MONS, V., CIENFUEGOS, J. A., MAGANTO, P., GOLITSIN, A., EROLES, G., CASTILLO-OLIVARES, J., and ARANA, J. M. SEGOVIA DE
- Abstract
We and others have reported that dispersed liver cells transplanted into the spleen parenchyma of syngeneic rats remained functional and viable for a long time. This report describes our results with hepatocellular transplantation as a therapeutic method in a model of fulminant hepatic failure (FHF) in the rat.
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- 1984
106. Capítulo 45 - Trasplante clínico de hepatocitos
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Cuervas-Mons, V.
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107. Capítulo 15 - Inmunosupresión en el trasplante hepático
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Cuervas-Mons, V.
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108. Recurrence of primary sclerosing cholangitis after liver transplantation: Analysing the European Liver Transplant Registry and beyond
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Visseren, Thijmen, Erler, Nicole Stephanie, Polak, Wojciech Grzegorz, Adam, René, Karam, Vincent, Vondran, Florian Wolfgang Rudolf, Ericzon, Bo‐Goran, Thorburn, Douglas, IJzermans, Jan Nicolaas Maria, Paul, Andreas, Heide, Frans, Taimr, Pavel, Nemec, Petr, Pirenne, Jacques, Romagnoli, Renato, Metselaar, Herold Johnny, Darwish Murad, Sarwa, Vondran, Florian, Bergquist, Annika, Lindström, Lina, Snowdon, Victoria, van der Heide, Frans, Trunecka, Pavel, Salizzoni, Mauro, Arendtsen Rostved, Andreas, Arenga, Giuseppe, Berlakovich, Gabriela A, Candinas, Daniel, Markovic, Sasa, Troisi, Roberto, van Hoek, Bart, Kanmaz, Turan, Dayangac, Murat, Berney, Thierry, Sforza, Daniele, Gridelli, Bruno, Clavien, Pierre‐Alain, Hoppe‐Lotichius, Maria, Senninger, Norbert, Lorf, Thomas, Settmacher, Utz, Cuervas‐Mons, Valentín, Bacakoğlu, Aylin, Nadalin, Silvio, Serra, Valentina, Pacholczyk, Marek, Baccarani, Umberto, Dopazo Taboada, Cristina, Berenguer, Marina, San Juan, Fernando, Detry, Olivier, Stippel, Dirk, Evrard, Philippe, Gugenheim, Jean, Kiliç, Murat, Fernández Selles, Carlos, Norena, Luis Antonio Herrera, Melandro, Fabio, Gonzalez‐Pinto, Ignacio, Nicolini, Daniele, Pardo Sánchez, Fernando, Neumann‐Haefelin, Christoph, Gastroenterology & Hepatology, Surgery, Epidemiology, Visseren, T., Erler, N. S., Polak, W. G., Adam, R., Karam, V., Vondran, F. W. R., Ericzon, B. -G., Thorburn, D., Ijzermans, J. N. M., Paul, A., van der Heide, F., Taimr, P., Nemec, P., Pirenne, J., Romagnoli, R., Metselaar, H. J., Darwish Murad, S., Vondran, F., Bergquist, A., Lindstrom, L., Snowdon, V., Trunecka, P., Salizzoni, M., Arendtsen Rostved, A., Arenga, G., Berlakovich, G. A., Candinas, D., Markovic, S., Troisi, R., van Hoek, B., Kanmaz, T., Dayangac, M., Berney, T., Sforza, D., Gridelli, B., Clavien, P. -A., Hoppe-Lotichius, M., Senninger, N., Lorf, T., Settmacher, U., Cuervas-Mons, V., Bacakoglu, A., Nadalin, S., Serra, V., Pacholczyk, M., Baccarani, U., Dopazo Taboada, C., Berenguer, M., San Juan, F., Detry, O., Stippel, D., Evrard, P., Gugenheim, J., Kilic, M., Fernandez Selles, C., Norena, L. A. H., Melandro, F., Gonzalez-Pinto, I., Nicolini, D., Pardo Sanchez, F., and Neumann-Haefelin, C.
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Registrie ,IMPACT ,medicine.medical_treatment ,Medizin ,030230 surgery ,Liver transplantation ,DISEASE ,0302 clinical medicine ,Risk Factors ,Recurrence ,Retrospective Studie ,EPIDEMIOLOGY ,Registries ,POPULATION ,bayesian statistics ,OUTCOMES ,disease recurrence ,liver transplantation ,patient and graft survival ,primary sclerosing cholangitis ,surgical procedures, operative ,Cohort ,primary sclerosing cholangiti ,030211 gastroenterology & hepatology ,Registry data ,Life Sciences & Biomedicine ,Human ,bayesian statistic ,medicine.medical_specialty ,Cholangitis, Sclerosing ,Detailed data ,Primary sclerosing cholangitis ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Science & Technology ,Proportional hazards model ,business.industry ,Risk Factor ,Bayes Theorem ,Patient survival ,NATURAL-HISTORY ,medicine.disease ,RISK-FACTORS ,Graft survival ,Surgery ,business - Abstract
Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival. ispartof: TRANSPLANT INTERNATIONAL vol:34 issue:8 pages:1455-1467 ispartof: location:Switzerland status: published
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- 2021
109. Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study
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Christophe Duvoux, Dirk Ysebaert, Federica Invernizzi, Damiano Patrono, Fernando Diaz-Fontenla, Frederick Berrevoet, Jacques Pirenne, Bo Göran Ericzon, G. Magini, François Faitot, Laura Lladó, Sara Conti, Valentín Cuervas-Mons, Pablo Mart Cruchaga, René Adam, Constantino Fondevila, Jordi Colmenero, Sylvie Radenne, Oliver Detry, C. Morelli, Sherrie Bhooori, Giovanni Perricone, Audrey Coilly, Paolo Cortesi, M. Zambelli, Lluis Castells, Vincent Karam, Wojciech G. Polak, Luca S. Belli, Carmelo Loinaz, Luciano De Carlis, Herold J. Metselaar, Gonzalo Rodriguez, Gastroenterology & Hepatology, Surgery, ELITA-ELTR COVID-19 Registry, Belli, L, Fondevila, C, Cortesi, P, Conti, S, Karam, V, Adam, R, Coilly, A, Ericzon, B, Loinaz, C, Cuervas-Mons, V, Zambelli, M, Llado, L, Diaz, F, Invernizzi, F, Patrono, D, Faitot, F, Bhooori, S, Pirenne, J, Perricone, G, Magini, G, Castells, L, Detry, O, Cruchaga, P, Colmenero, J, Berrevoet, F, Rodriguez, G, Ysebaert, D, Radenne, S, Metselaar, H, Morelli, C, De Carlis, L, Polak, W, and Duvoux, C
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medicine.medical_specialty ,Liver transplantation ,Hepatology ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Gastroenterology ,COVID-19 ,Immunosuppression ,medicine.disease ,Comorbidity ,Tacrolimus ,Respiratory failure ,SDG 3 - Good Health and Well-being ,Tacrolimu ,Internal medicine ,Diabetes mellitus ,medicine ,Human medicine ,business ,Outcome ,Kidney disease - Abstract
BACKGROUND AND AIMS: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking. METHODS: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis. RESULTS: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose. ispartof: GASTROENTEROLOGY vol:160 issue:4 pages:1151-+ ispartof: location:United States status: published
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- 2021
110. COVID-19 in liver transplant recipients: preliminary data from the ELITA/ELTR registry
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Vincent Karam, Sara Conti, Luisa Pasulo, Lluis Castells, Olga Ciccarelli, Valentín Cuervas-Mons, Luca S. Belli, Victor Lopez-Lopez, René Adam, Federica Invernizzi, Damiano Patrono, C. Fondevila, Wojchiech Polak, Carmelo Loinaz, Christophe Duvoux, Maria Cristina Morelli, Sherrie Bhoori, Belli, L, Duvoux, C, Karam, V, Adam, R, Cuervas-Mons, V, Pasulo, L, Loinaz, C, Invernizzi, F, Patrono, D, Bhoori, S, Ciccarelli, O, Morelli, M, Castells, L, Lopez-Lopez, V, Conti, S, Fondevila, C, Polak, W, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, and Surgery
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Adult ,Male ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Adolescent ,medicine.medical_treatment ,Pneumonia, Viral ,MEDLINE ,Liver transplantation ,Article ,Betacoronavirus ,Immunocompromised Host ,Young Adult ,Risk Factors ,Internal medicine ,Pandemic ,medicine ,Humans ,liver transplant recipients ,Registries ,Young adult ,Child ,Pandemics ,Aged ,Aged, 80 and over ,biology ,Hepatology ,business.industry ,SARS-CoV-2 ,Gastroenterology ,COVID-19 ,Middle Aged ,medicine.disease ,biology.organism_classification ,Liver Transplantation ,Europe ,Pneumonia ,surgical procedures, operative ,Female ,business ,Coronavirus Infections ,Preliminary Data - Abstract
Whether liver transplant recipients are at a particularly high risk for critical COVID-19 needs clarification. To date, data are scarce1, 2, 3, 4 and results conflicting. On March 30, 2020, the European Liver and Intestine Transplantation Association (ELITA) sent out a call to establish a COVID-19 registry for liver transplant recipients to 149 liver transplant centres affiliated to the European Liver Transplant Registry (ELTR) located in 30 European countries. 114 (77%) centres responded to the call, with 56 (49%) of these having observed cases of COVID-19 in their liver transplant recipients. [...]
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- 2020
111. Utility of hepatocellular transplantation into spleen as a temporary liver support in cirrhotic dogs
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Benito, J.Martín, Colás, A., and Cuervas-Mons, V.
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- 1990
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112. Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations
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Álvaro Pascual, Domingo Hernández, Francisco López-Medrano, Pilar Martín-Dávila, Rafael Cantón, M.J. Goyanes, Belén Gutiérrez-Gutiérrez, Elisa Vidal, A. Solé-Jover, J. Fortún, Patricia Muñoz, Julián Torre-Cisneros, Rafael López-Andújar, Oscar Len, A. Román-Broto, Antonio Oliver, Valentín Cuervas-Mons, Miguel Montejo, Mario Fernández-Ruiz, Joan Gavaldà, Emilia Cercenado, Carlota Gudiol, A. Moreno, Elena Pérez-Nadales, Juan José Castón, Elisa Cordero, Rafael San-Juan, Daniel Serón, Carlos Cervera, J.T. Silva, María G. Crespo-Leiro, Luis Martínez-Martínez, Benito Almirante, José María Aguado, Luis Almenar, M.C. Fariñas, Maricela Valerio, J. Elizalde-Fernández, José Miguel Cisneros, Jordi Carratalà, Universidad de Cantabria, Universitat de Barcelona, [Aguado, J. M.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [Fernandez-Ruiz, M.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [Lopez-Medrano, F.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [San-Juan, R.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [Silva, J. T.] Univ Extremadura, Fdn Formac & Invest Profes Salud Extremadura Fund, Univ Hosp Badajoz, Dept Infect Dis, Badajoz, Spain, [Cordero, E.] Univ Seville, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville, IBiS,Univ Hosp Virgen Rocio,CSIC, Seville, Spain, [Cisneros, J. M.] Univ Seville, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville, IBiS,Univ Hosp Virgen Rocio,CSIC, Seville, Spain, [Fortun, J.] Univ Hosp Ramon & Cajal, Dept Infect Dis, Madrid, Spain, [Martin-Davila, P.] Univ Hosp Ramon & Cajal, Dept Infect Dis, Madrid, Spain, [Gudiol, C.] Univ Barcelona, Dept Infect Dis, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge IDIBELL, Barcelona, Spain, [Carratala, J.] Univ Barcelona, Dept Infect Dis, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge IDIBELL, Barcelona, Spain, [Martinez-Martinez, L.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Microbiol, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Vidal, E.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Caston, J. J.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Perez-Nadales, E.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Torre-Cisneros, J.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Almenar, L.] Hosp Univ La Fe, Cardiol Dept, Heart Failure & Heart Transplant Unit, Valencia, Spain, [Almirante, B.] Univ Autonoma Barcelona, Dept Infect Dis, Hosp Univ Vail Hebron, Barcelona, Spain, [Gavalda, J.] Univ Autonoma Barcelona, Dept Infect Dis, Hosp Univ Vail Hebron, Barcelona, Spain, [Len, O.] Univ Autonoma Barcelona, Dept Infect Dis, Hosp Univ Vail Hebron, Barcelona, Spain, [Canton, R.] Univ Hosp Ramon & Cajal, Microbiol Dept, IRYCIS, Madrid, Spain, [Cercenado, E.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Goyanes, M. J.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Valerio, M.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Munoz, P.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Cercenado, E.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Goyanes, M. J.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Valerio, M.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Munoz, P.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Cercenado, E.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Goyanes, M. J.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Valerio, M.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Munoz, P.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Cervera, C.] Univ Alberta, Div Infect Dis, Dept Med, Edmonton, AB, Canada, [Crespo-Leiro, M. G.] Complexo Hosp Univ A Coruna, Cardiol Dept, La Coruna, Spain, [Cuervas-Mons, V.] Hosp Clin Puerto Hierro, Liver Transplantat Internal Med, Madrid, Spain, [Elizalde-Fernandez, J.] Hosp Navarra, Intens Care Unit, Pamplona, Spain, [Farinas, M. C.] Univ Cantabria, Univ Hosp Marques Valdecilla, Unit Infect Dis, Santander, Spain, [Gutierrez-Gutierrez, B.] Univ Seville, Clin Unit Infect Dis & Microbiol, Unidad Gest Clin Enfermedades Infecciosas & Micro, Inst Biomed Sevilla,Hosp Univ Virgen Macarena,IBi, Seville, Spain, [Pascual, A.] Univ Seville, Clin Unit Infect Dis & Microbiol, Unidad Gest Clin Enfermedades Infecciosas & Micro, Inst Biomed Sevilla,Hosp Univ Virgen Macarena,IBi, Seville, Spain, [Hernandez, D.] Univ Malaga, Dept Nephrol, Carlos Haya Reg Univ Hosp, Inst Biomed Res Malaga IBIMA, Malaga, Spain, [Lopez-Andujar, R.] Hosp Univ & Politecn La Fe, Gen Surg Serv, Hepatobiliopancreat Surg & Transplantat Unit, Valencia, Spain, [Montejo, M.] Univ Hosp Cruces, Unit Infect Dis, Bilbao, Spain, [Moreno, A.] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain, [Oliver, A.] Hosp Son Espases, Inst Invest Sanitaria Palma IdISPa, Dept Microbiol, Palma de Mallorca, Spain, [Oliver, A.] Hosp Son Espases, Inst Invest Sanitaria Palma IdISPa, Res Unit, Palma de Mallorca, Spain, [Roman-Broto, A.] Univ Autonoma Barcelona, Hosp Univ Vall Hebron, Lung Transplant Unit, Barcelona, Spain, [Seron, D.] Hosp Univ Vall Hebron, Nephrol Dept, Barcelona, Spain, [Sole-Jover, A.] Hosp Univ La Fe, Dept Pneumol, Lung Transplant Unit, Valencia, Spain, Spanish Ministry of Economy and Competitiveness, Institute de Salud Carlos III, and Fundacion pars la Formacion e Investigacion de los Profesionales de la Salud de Extremadura (FundeSalud), Institute de Salud Carlos III
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0301 basic medicine ,medicine.medical_treatment ,Antibiotics ,Carbapenem-resistant enterobacteriaceae ,Communicable diseases ,Organ transplantation ,Lactamase-producing enterobacteriaceae ,Postoperative Complications ,Solid organ transplantation ,Medicine ,Blood-stream infections ,Kidney transplantation ,Transplantation of organs ,Carbapenem-resistant Gram-negative bacilli ,High-risk patients ,Multidrug resistant Gram-negative bacilli ,Disease Management ,Drug Resistance, Multiple ,Tissue Donors ,Anti-Bacterial Agents ,Pseudomonas-aeruginosa bacteremia ,medicine.medical_specialty ,medicine.drug_class ,030106 microbiology ,Urinary-tract-infections ,03 medical and health sciences ,Surgical prophylaxis ,Acinetobacter-baumannii infections ,Pseudomonas ,Ventilator-associated pneumonia ,Lung transplantation ,Humans ,Extended-spectrum β-lactamases ,Intensive care medicine ,Contraindication ,Transplantation ,business.industry ,Bacils ,Extensively-drug-resistant ,Organ Transplantation ,Malalties infeccioses ,medicine.disease ,Transplant Recipients ,Trasplantament d'òrgans ,Bacillus (Bacteria) ,Spectrum beta-lactamases ,Intensive-care-unit ,business ,Gram-Negative Bacterial Infections - Abstract
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection. J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.
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- 2017
113. Reversibility of fibrosis
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TARANTINO, Giuseppe, CRAXI, Antonio, MORENO-OTERO R, ALBILLOS A, BANARES R, CUERVAS-MONS V, MEDINA J, TARANTINO G, and CRAXI' A
- Published
- 2006
114. Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.
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Dongelmans E, Erler N, Adam R, Nadalin S, Karam V, Yilmaz S, Kelly C, Pirenne J, Acarli K, Allison M, Hakeem A, Dhakshinamoorthy V, Fedaruk D, Rummo O, Kilic M, Nordin A, Fischer L, Parente A, Mirza D, Bennet W, Tokat Y, Faitot F, Antonelli BB, Berlakovich G, Patch D, Berrevoet F, Ribnikar M, Gerster T, Savier E, Gruttadauria S, Ericzon BG, Valdivieso A, Cuervas-Mons V, Perez Saborido B, Croner RS, De Carlis L, Magini G, Rossi R, Popescu I, Razvan L, Schneeberger S, Blokzijl H, Llado L, Gomez Bravo MA, Duvoux C, Mezjlík V, Oniscu GC, Pearson K, Dayangac M, Lucidi V, Detry O, Rotellar F, den Hoed C, Polak WG, and Darwish Murad S
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- Humans, Male, Female, Europe epidemiology, Adult, Middle Aged, Treatment Outcome, Young Adult, Adolescent, Retrospective Studies, Budd-Chiari Syndrome surgery, Liver Transplantation statistics & numerical data, Registries statistics & numerical data, Graft Survival
- Abstract
Background and Aims: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe., Approach and Results: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%)., Conclusions: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes., (Copyright © 2024 American Association for the Study of Liver Diseases.)
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- 2024
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115. Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.
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Martin-Mateos R, Martínez-Arenas L, Carvalho-Gomes Á, Aceituno L, Cadahía V, Salcedo M, Arias A, Lorente S, Odriozola A, Zamora J, Blanes M, Len Ó, Benítez L, Campos-Varela I, González-Diéguez ML, Lázaro DR, Fortún J, Cuadrado A, Carrasco NM, Rodríguez-Perálvarez M, Álvarez-Navascues C, Fábrega E, Serrano T, Cuervas-Mons V, Rodríguez M, Castells L, Berenguer M, Graus J, and Albillos A
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- Humans, Male, Middle Aged, Female, Risk Factors, Retrospective Studies, Prevalence, Spain epidemiology, Postoperative Complications epidemiology, Postoperative Complications microbiology, Enterococcus faecium isolation & purification, Aged, Incidence, Anti-Bacterial Agents therapeutic use, Urinary Tract Infections epidemiology, Urinary Tract Infections microbiology, Urinary Tract Infections etiology, Liver Transplantation adverse effects, Drug Resistance, Multiple, Bacterial, Bacterial Infections epidemiology, Bacterial Infections etiology
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Background & Aims: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT)., Methods: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT., Results: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates., Conclusion: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors., Impact and Implications: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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- 2024
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116. COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.
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Moreno-Torres V, Martínez-Urbistondo M, Calderón-Parra J, Mills P, Muñoz-Serrano A, Arias-Milla A, Benítez L, Aguilar-Pérez M, Múñez-Rubio E, Ramos-Martínez A, Fernández-Cruz A, Cuervas-Mons V, and de Mendoza C
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- Adult, Humans, Retrospective Studies, Transplant Recipients, Registries, COVID-19 epidemiology, Organ Transplantation adverse effects
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Objectives: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19., Methods: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list., Results: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98)., Conclusion: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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117. Long term SARS-CoV-2-specific cellular immunity after COVID-19 in liver transplant recipients.
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Citores MJ, Caballero-Marcos A, Cuervas-Mons V, Alonso-Fernández R, Graus-Morales J, Arias-Milla A, Valerio M, Muñoz P, and Salcedo M
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- Humans, SARS-CoV-2, COVID-19 Testing, Leukocytes, Mononuclear, Immunity, Cellular, Immunoglobulin G, Antibodies, Viral, COVID-19, Liver Transplantation
- Abstract
Purpose: Long-term immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunosuppressed patients is not well characterized. We aimed to explore the long-term natural immunity against SARS-CoV-2 in liver transplant (LT) recipients compared to the non-transplanted population (control group)., Methods: Fifteen LT recipients and 15 controls matched according to variables associated with disease severity were included at 12 months following the coronavirus disease 2019 (COVID-19) onset. Peripheral blood mononuclear cells were stimulated with peptide pools covering spike (S), nucleocapside (N), and membrane (M) proteins. Reactive CD4+ and CD8+ T cells were identified using flow cytometry, and cytokine production was evaluated in the culture supernatants using cytometric bead array. Serum anti-N and anti-S IgG antibodies were detected with chemiluminescence., Results: The percentage of patients with a positive response in both CD4+ and CD8+ T cells against each viral protein and IL2, IL10, TNF-α, and IFN-γ levels was similar between LT recipients and controls. IFN-γ levels were positively correlated with the percentage of reactive CD4+ (p = 0.022) and CD8+ (p = 0.043) T cells to a mixture of M + N + S peptide pools. The prevalence and levels of anti-N and anti-S IgG antibodies were slightly lower in the LT recipients, but the difference was not statistically significant., Conclusion: LT recipients exhibited a similar T cell response compared to non-transplanted individuals one year after COVID-19 diagnosis., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)
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- 2023
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118. Usefulness of Systemic Venous Ultrasound Protocols in the Prognosis of Heart Failure Patients: Results from a Prospective Multicentric Study.
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Torres-Arrese M, Mata-Martínez A, Luordo-Tedesco D, García-Casasola G, Alonso-González R, Montero-Hernández E, Cobo-Marcos M, Sánchez-Sauce B, Cuervas-Mons V, and Tung-Chen Y
- Abstract
Mortality and re-admission rates for decompensated acute heart failure (AHF) is increasing overall and risk stratification might be challenging. We sought to evaluate the prognostic role of systemic venous ultrasonography in patients hospitalized for AHF. We prospectively recruited 74 AHF patients with a NT-proBNP level above 500 pg/mL. Then, multi-organ ultrasound assessments (lung, inferior vena cava (IVC), pulsed-wave Doppler (PW-Doppler) of hepatic, portal, intra-renal and femoral veins) were performed at admission, discharge, and follow-up (for 90 days). We also calculated the Venous Excess Ultrasound System (VExUS), a new score of systemic congestion based on IVC dilatation and pulsed-wave Doppler morphology of hepatic, portal and intra-renal veins. An intra-renal monophasic pattern (area under the curve (AUC) 0.923, sensitivity (Sn) 90%, specificity (Sp) 81%, positive predictive value (PPV) 43%, and negative predictive value (NPV) 98%), a portal pulsatility > 50% (AUC 0.749, Sn 80%, Sp 69%, PPV 30%, NPV 96%) and a VExUS score of 3 corresponding to severe congestion (AUC 0.885, Sn 80%, Sp 75%, PPV 33%, and NPV 96%) predicted death during hospitalization. An IVC above 2 cm (AUC 0.758, Sn 93.l% and Sp 58.3) and the presence of an intra-renal monophasic pattern (AUC 0. 834, sensitivity 0.917, specificity 67.4%) in the follow-up visit predicted AHF-related re-admission. Additional scans during hospitalization or the calculation of a VExUS score probably adds unnecessary complexity to the assessment of AHF patients. In conclusion, VExUS score does not contribute to the guidance of therapy or the prediction of complications, compared with the presence of an IVC greater than 2 cm, a venous monophasic intra-renal pattern or a pulsatility > 50% of the portal vein in AHF patients. Early and multidisciplinary follow-up visits remain necessary for the improvement of the prognosis of this highly prevalent disease.
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- 2023
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119. Role of TGF-β1 +869T>C polymorphism in renal dysfunction one year after heart transplantation.
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López-Ibor JV, Citores MJ, Portoles J, Gómez-Bueno M, Sánchez-Sobrino B, Muñoz A, Cuervas-Mons V, and Segovia-Cubero J
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- Female, Humans, Male, Calcineurin Inhibitors, Genetic Predisposition to Disease, Genotype, Polymorphism, Genetic, Adult, Middle Aged, Heart Transplantation, Renal Insufficiency, Chronic genetics, Transforming Growth Factor beta1 genetics
- Abstract
Background: Chronic kidney disease is a major complication after heart transplantation with wide inter-individual variability. Calcineurin inhibitor nephrotoxicity, mediated by transforming growth factor-beta1 (TGF-β1), is an important contributing factor. Our objective was to evaluate the association between TGF-β1 polymorphisms and renal dysfunction 1-year after heart transplantation., Methods: Single-center observational study that included patients who received a first heart transplant between 1990-2013. According to the 1-year eGFR decline, patients were classified as "Stable" (decrease in eGFR<10% or eGFR>60 ml/min/1.73m2) or "Progressors" (decrease in eGFR>10% and eGFR<60 ml/min/1.73m2). "Progressors" were then subdivided by the degree of eGFR decrease in "Mild progressors" (10-30%) or "Rapid progressors" (>30%). The association between TGF-β1 +869T>C polymorphism and other risk factors with the eGFR outcome was analysed., Results: A total of 355 patients (78% male; 50.7 ± 11.8 years) were included. According to the 1-year eGFR decline, 220 patients (62%) were classified as "Stable" and 135 (38%) as "Progressors". TGF-β1+869CC genotype was more prevalent in "Stable" vs "Progressors" group (20% vs 8%, p = 0.009). In the multivariate analysis, female sex (p 0.02) and eGFR<60 ml/min/1.73 m2 at first month post-heart transplant (p = 0.004) remained as risk factors of eGFR decline, and TGF-β1 + 869CC genotype (p = 0.001) and renal dysfunction pre-heart transplant (p = 0.04) as protective factors. TGF-β1 + 869CC genotype was less frequently found in "Mild progressors" compared to "Rapid progressors" [p = 0.019; OR (95%CI) = 0.19 (.05-.76)]., Conclusions: The TGF-β1 +869CC genotype is associated with a lower risk of calcineurin inhibitor nephrotoxicity after heart transplant. This genetic susceptibility could enable a more personalized patient treatment., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2022
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120. Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study.
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Gómez-Bravo M, Prieto Castillo M, Navasa M, Sánchez-Antolín G, Lladó L, Otero A, Serrano T, Jiménez Romero C, García González M, Valdivieso A, González-Diéguez ML, de la Mata M, Pons JA, Salcedo M, Rodrigo JM, Cuervas-Mons V, González Rodríguez A, Caralt M, Pardo F, Varo Pérez E, Crespo G, Rubin Á, Guilera M, Aldea A, and Santoyo J
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- Drug Therapy, Combination, Everolimus adverse effects, Graft Rejection etiology, Graft Rejection prevention & control, Graft Survival, Humans, Immunosuppressive Agents adverse effects, Kidney, Mycophenolic Acid adverse effects, Prospective Studies, Liver Transplantation adverse effects, Tacrolimus adverse effects
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Background and Aim: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain., Methods: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated., Results: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups., Conclusion: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.
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- 2022
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121. Decreased Long-Term Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Immunity in Liver Transplantation Recipients 12 Months After Coronavirus Disease 2019.
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Caballero-Marcos A, Citores MJ, Alonso-Fernández R, Rodríguez-Perálvarez M, Valerio M, Graus Morales J, Cuervas-Mons V, Cachero A, Loinaz-Segurola C, Iñarrairaegui M, Castells L, Pascual S, Vinaixa-Aunés C, González-Grande R, Otero A, Tomé S, Tejedor-Tejada J, Fernández-Yunquera A, González-Diéguez L, Nogueras-Lopez F, Blanco-Fernández G, Díaz-Fontenla F, Bustamante FJ, Romero-Cristóbal M, Martin-Mateos R, Arias-Milla A, Calatayud L, Marcacuzco-Quinto AA, Fernández-Alonso V, Gómez-Gavara C, Muñoz P, Bañares R, Pons JA, and Salcedo M
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- Antibodies, Viral blood, COVID-19 Vaccines, Humans, Immunoglobulin G blood, Prospective Studies, SARS-CoV-2, COVID-19 immunology, Immunity, Humoral, Liver Transplantation
- Abstract
Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients., (© 2021 by the American Association for the Study of Liver Diseases.)
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- 2022
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122. Emergency department frequentation and unscheduled readmissions within the first year after liver transplantation, and their impact on survival.
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Molina Ávila P, Citores Sánchez MJ, Arias Milla A, Benítez L, Montero Herández E, and Cuervas Mons V
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- Emergency Service, Hospital, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Liver Transplantation, Patient Readmission
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The aim of this study was to assess emergency room frequentation, visit causes, and unscheduled readmissions within the first year after discharge from hospital following liver transplantation. Their impact on graft and patient survival was also assessed. This was a retrospective study of the medical records of 98 patients (mean age, 55.6 ± 8.59 years, 77.6 % males) who were consecutively discharged from hospital after undergoing a first liver transplant in our institution during 2012-2015. All visits to the emergency room during the first years after transplantation were analyzed, and survival at two years after transplantation was calculated. Fifty-six of the 98 patients (57.15 %) visited the emergency room on 117 occasions within the first year post-transplantation. Fever (n = 34; 29.05 %) and digestive symptoms (n = 32; 27.35 %) were the most common causes of consultation, and resulted in over half of visits. Thirty-five of these 56 patients (62.5 %) required an urgent readmission during 50 of the 117 (42.7 %) visits. This was primarily due to infectious complications (44 %) of diverse causes (bacterial pneumonia, cholangitis, Clostridium difficile colitis) and biliary tract-related issues. The likelihood of readmission increased from 11.22 % at 30 days after discharge to 22.4 % at 90 days after discharge. Patient survival at 1 and 2 years after transplantation was lower for patients who were readmitted (88.4 % and 80.7 %, respectively) when compared to those who were not readmitted (95.56 % and 91.17 %, respectively, p = 0.002).
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- 2022
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123. Bacterial infections in patients hospitalized with COVID-19.
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Moreno-Torres V, de Mendoza C, de la Fuente S, Sánchez E, Martínez-Urbistondo M, Herráiz J, Gutiérrez A, Gutiérrez Á, Hernández C, Callejas A, Maínez C, Royuela A, and Cuervas-Mons V
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- Humans, Pandemics, SARS-CoV-2, Bacterial Infections epidemiology, COVID-19 complications, Respiratory Distress Syndrome
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Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of bacterial infections were examined in patients consecutively admitted with COVID-19 at one tertiary hospital in Madrid between March 1st and April 30th, 2020. Among 1594 hospitalized patients with COVID-19, 135 (8.5%) experienced bacterial infectious events, distributed as follows: urinary tract infections (32.6%), bacteremia (31.9%), pneumonia (31.8%), intra-abdominal infections (6.7%) and skin and soft tissue infections (6.7%). Independent predictors of bacterial infections were older age, neurological disease, prior immunosuppression and ICU admission (p < 0.05). Patients with bacterial infections who more frequently received steroids and tocilizumab, progressed to lower Sap02/FiO2 ratios, and experienced more severe ARDS (p < 0.001). The mortality rate was significantly higher in patients with bacterial infections as compared to the rest (25% vs 6.7%, respectively; p < 0.001). In multivariate analyses, older age, prior neurological or kidney disease, immunosuppression and ARDS severity were associated with an increased mortality (p < 0.05) while bacterial infections were not. Conversely, the use of steroids or steroids plus tocilizumab did not confer a higher risk of bacterial infections and improved survival rates. Bacterial infections occurred in 8.5% of patients hospitalized with COVID-19 during the first wave of the pandemic. They were not independently associated with increased mortality rates. Baseline COVID-19 severity rather than the incidence of bacterial infections seems to contribute to mortality. When indicated, the use of steroids or steroids plus tocilizumab might improve survival in this population., (© 2021. The Author(s).)
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- 2022
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124. Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry.
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Calderón-Parra J, Cuervas-Mons V, Moreno-Torres V, Rubio-Rivas M, Blas PA, Pinilla-Llorente B, Helguera-Amezua C, Jiménez-García N, Pesqueira-Fontan PM, Méndez-Bailón M, Artero A, Gilabert N, Ibánez-Estéllez F, Freire-Castro SJ, Lumbreras-Bermejo C, and Antón-Santos JM
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- Adrenal Cortex Hormones adverse effects, Hospital Mortality, Humans, Registries, Retrospective Studies, SARS-CoV-2, Calcineurin Inhibitors adverse effects, COVID-19 Drug Treatment
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Objectives: The aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19., Methods: The study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality., Results: Out of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43-2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43-3.82)., Conclusions: Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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125. Risk Factors for Clostridioides Difficile Diarrhea In Solid Organ Transplantation Recipients.
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Ortiz-Balbuena J, Royuela A, Calderón-Parra J, Martínez-Ruiz R, Asensio-Vegas Á, Múñez E, Valencia-Alijo Á, Gutiérrez-Rojas Á, Ussetti P, Cuervas-Mons V, Segovia-Cubero J, Portolés-Pérez J, and Ramos-Martínez A
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- Adult, Aged, Case-Control Studies, Clostridioides, Diarrhea, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Transplant Recipients, Clostridioides difficile, Clostridium Infections diagnosis, Clostridium Infections epidemiology, Organ Transplantation adverse effects
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Background: There is limited knowledge about risk factors for Clostridioides difficile infection (CDI) and recurrent CDI in solid organ transplant (SOT) recipients., Methods: A case-control study of CDI in SOT recipients compared with controls (SOT recipients who did not present CDI)., Results: Sixty-seven patients from 1089 SOT recipients (6.2%) suffered at least one episode of CDI. The mean age was 55 ± 12 years and 20 cases (69%) were men. The accumulated incidence was 8% in liver transplantation, 6.2% in lung transplantation, 5.4% in heart transplantation, and 4.7% in kidney transplantation. Twenty-nine cases (43.3%) were diagnosed during the first 3 months after SOT. Forty-one cases (61.2%) were hospital acquired. Thirty-one patients with CDI presented with mild-moderate infection (46.3%), 30 patients with severe infection (44.8%), and 6 patients with severe-complicated disease (9%). Independent variables found to be related with CDI were hospitalization in the previous 3 months (odds ratio: 2.99; [95% confidence interval 1.21-7.37]) and the use of quinolones in the previous month (odds ratio: 3.71 [95% confidence interval 1.16-11.8]). Eleven patients (16.4%) had at least one recurrence of CDI. Previous treatment with amoxicillin-clavulanate, severe-complicated index episode, and high serum creatinine were associated with recurrent CDI in the univariant analysis CONCLUSIONS: Liver transplant recipients presented the highest incidence of CDI among SOT recipients. Risk factors for CDI were hospitalization in the previous 3 months and the use of quinolones in the previous month., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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126. Coronavirus Disease 2019 (COVID-19) in Solid Organ Transplant Recipients: A Case-Control Study.
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Muñoz Serrano A, Arias A, Moreno-Torres V, Calderón J, Vicente N, and Cuervas-Mons V
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- Case-Control Studies, Humans, Retrospective Studies, SARS-CoV-2, Transplant Recipients, COVID-19, Organ Transplantation adverse effects
- Abstract
BACKGROUND It is unclear whether solid organ transplant (SOT) patients have more severe coronavirus disease 2019 (COVID-19) and worse outcome than the general population. MATERIAL AND METHODS We conducted a case-control study on 32 SOT recipients and 84 non-SOT controls matched for age and sex admitted for confirmed COVID-19. The primary endpoint was in-hospital all-cause mortality rate. Secondary endpoints included severe acute respiratory distress syndrome (ARDS), use of high-flow oxygen therapy, and length of hospital stay. RESULTS The median (IQR) Charlson comorbidity index (CCI) at admission was significantly higher in SOT recipients (6 (3-8) vs 3 (2-4); P<0.01). Fever was less frequent in SOT recipients (78% vs 94%, P=0.01). SOT recipients had a higher median SaO2/FiO2 at admission (452 [443-462] vs 443 [419-452], P<0.01) and reached the worst SaO2/FiO2 value later during hospitalization 15 (10-21) vs 11 (9-14) days, P=0.01). Both groups had a similar severe ARDS rate during hospitalization (33% vs 28%) (p=0.59). There were no significant differences during hospitalization in terms of highest level of respiratory support needed, or length of hospital stay: 8.5 (5.5-21) vs 11.5 (6.5-16.5) days; P=0.34) in SOT recipients when compared to controls. In-hospital all-cause mortality rates were significantly higher in SOT recipients (21.9% vs 4.7%, P<0.01; OR 1.08; 95% CI 0.10-10.98), but among patients who died, median CCI was similar between groups (8 [6-8] vs 7 [6-8]). CONCLUSIONS In our experience, hospitalized SOT recipients for COVID-19 had higher in-hospital mortality compared to non-SOT patients, probably due to the greater number of underlying comorbidities, and not directly related to chronic immunosuppression.
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- 2021
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127. Autoimmune Extrahepatic Disorders in Patients With Autoimmune Liver Disease.
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Contreras GV, Marugan MT, and Cuervas-Mons V
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- Adult, Female, Humans, Retrospective Studies, Severity of Illness Index, Cholangitis, Sclerosing complications, Cholangitis, Sclerosing surgery, End Stage Liver Disease, Hepatitis, Autoimmune complications, Hepatitis, Autoimmune diagnosis, Inflammatory Bowel Diseases
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Background: Autoimmune liver diseases (ALDs) (primary biliary cholangitis, primary sclerosing cholangitis [PSC], autoimmune hepatitis [AIH]) can present extrahepatic autoimmune manifestations, the most frequent being inflammatory bowel disease (IBD), autoimmune thyroid disease, and Sjögren syndrome (SS)., Methods: Retrospective study of patients who have undergone liver transplant (LT) with post-LT follow-up of at least 2 years. Descriptive analysis of clinical variables and overall and graft survival., Results: ALD was an infrequent indication for LT (68 of 835, 8%), 39 primary biliary cholangitis, 17 AIH, and 12 PSC; 56 were women. The mean (standard deviation [SD]) pre-LT Model for End-Stage Liver Disease score was 17 (5.4). The mean (SD) age of LT recipients at LT was 40 (21) years. A total of 27 patients presented extrahepatic autoimmune diseases. The most frequent was IBD in 7 patients, preferentially in patients with PSC (10/12), followed by Sjögren syndrome and autoimmune thyroid disease. IBD was present in 12 patients: 8 ulcerative colitis (6 PSC and 2 AIH overlap syndrome), 2 Crohn disease both PSC, and another 2 PSC and IBD without conclusive diagnosis (neither for ulcerative colitis nor Crohn disease). Five presented IBD de novo post-LT; the other 7 debuted before LT. In 3 of these 7 patients with pre-LT IBD, the disease went into remission after LT. Colectomy was necessary in 3 patients. No statistically significant findings were found in the survival analysis., Conclusions: ALD is an infrequent reason for LT. Extrahepatic autoimmune diseases are associated in these patients, with IBD being the most frequent. IBD presents a torpid course but does not impact overall survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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128. Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients.
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Caballero-Marcos A, Salcedo M, Alonso-Fernández R, Rodríguez-Perálvarez M, Olmedo M, Graus Morales J, Cuervas-Mons V, Cachero A, Loinaz-Segurola C, Iñarrairaegui M, Castells L, Pascual S, Vinaixa-Aunés C, González-Grande R, Otero A, Tomé S, Tejedor-Tejada J, Álamo-Martínez JM, González-Diéguez L, Nogueras-Lopez F, Blanco-Fernández G, Muñoz-Bartolo G, Bustamante FJ, Fábrega E, Romero-Cristóbal M, Martin-Mateos R, Del Rio-Izquierdo J, Arias-Milla A, Calatayud L, Marcacuzco-Quinto AA, Fernández-Alonso V, Gómez-Gavara C, Colmenero J, Muñoz P, and Pons JA
- Subjects
- Female, Humans, Immunity, Humoral, Prospective Studies, SARS-CoV-2, Transplant Recipients, COVID-19, Liver Transplantation
- Abstract
The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2021
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129. Major determinants of death in patients hospitalized with COVID-19 during the first epidemic wave in Madrid, Spain.
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Moreno-Torres V, de la Fuente S, Mills P, Muñoz A, Muñez E, Ramos A, Fernández-Cruz A, Arias A, Pintos I, Vargas JA, Cuervas-Mons V, and de Mendoza C
- Subjects
- Age Factors, Aged, COVID-19 therapy, Critical Care methods, Female, Hospitalization statistics & numerical data, Humans, Length of Stay, Male, Middle Aged, Quarantine, Retrospective Studies, SARS-CoV-2, Spain epidemiology, COVID-19 mortality, Hospital Mortality, Pandemics
- Abstract
Abstract: Spain is one of the European countries most largely affected by COVID-19, being Madrid the epicenter. A good knowledge of the main features of hospitalized patients during the complete lockdown should improve the management of new COVID-19 surges.All patients hospitalized at one large tertiary hospital in Madrid for suspected COVID-19 pneumonia from March 1 to May 31 were retrospectively identified.A total of 1752 patients were admitted with suspected pneumonia due to SARS-CoV-2 infection during the 3-month study period. The peak of daily admissions (n = 84) was reached on March 24, whereas the maximal cumulative number of hospitalized patients (n = 626) occurred on March 30. Overall, 85.3% had a positive PCR test for SARS-CoV-2 at least once during admission. Their median age was 65 (54-77) and 59.9% were male. The median length of hospitalization was of 7 (4-13) days. Roughly 6.5% were admitted at the intensive care unit.Death occurred in 242 (13.8%). Overall, 75% of deaths occurred in patients older than 75 years-old. It was 38.2% in patients hospitalized older than 80 years-old versus 2.2% in patients younger than 60 years-old (p < 0.001). Up to 94 (38.8%) of deceased patients had been transferred from nursing homes. The median Charlson co-morbidity score was 6 in deceased patients.The in-hospital mortality rate during the first wave of COVID-19 in Madrid was 14%. It was largely driven by older age, the presence of underlying chronic conditions (≥2) and living at nursing homes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2021
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130. Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.
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Belli LS, Fondevila C, Cortesi PA, Conti S, Karam V, Adam R, Coilly A, Ericzon BG, Loinaz C, Cuervas-Mons V, Zambelli M, Llado L, Diaz-Fontenla F, Invernizzi F, Patrono D, Faitot F, Bhooori S, Pirenne J, Perricone G, Magini G, Castells L, Detry O, Cruchaga PM, Colmenero J, Berrevoet F, Rodriguez G, Ysebaert D, Radenne S, Metselaar H, Morelli C, De Carlis LG, Polak WG, and Duvoux C
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- Adult, Age Factors, Aged, Comorbidity, Female, Hospitalization, Humans, Liver Transplantation mortality, Male, Middle Aged, Proportional Hazards Models, Thrombosis prevention & control, COVID-19 complications, Immunosuppressive Agents therapeutic use, Liver Transplantation adverse effects, SARS-CoV-2, Tacrolimus therapeutic use
- Abstract
Background and Aims: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking., Methods: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis., Results: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2021
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131. COVID-19 in liver transplant recipients: preliminary data from the ELITA/ELTR registry.
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Belli LS, Duvoux C, Karam V, Adam R, Cuervas-Mons V, Pasulo L, Loinaz C, Invernizzi F, Patrono D, Bhoori S, Ciccarelli O, Morelli MC, Castells L, Lopez-Lopez V, Conti S, Fondevila C, and Polak W
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Betacoronavirus, COVID-19, Child, Europe, Female, Humans, Immunocompromised Host, Male, Middle Aged, Pandemics, Preliminary Data, Registries, Risk Factors, SARS-CoV-2, Young Adult, Coronavirus Infections diagnosis, Liver Transplantation, Pneumonia, Viral diagnosis
- Published
- 2020
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132. Mast cell-mediated splanchnic cholestatic inflammation.
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Aller MÁ, Martínez V, Arias A, Nava MP, Cuervas-Mons V, Vergara P, and Arias J
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- Animals, Male, Rats, Rats, Wistar, Cholestasis etiology, Inflammation etiology, Mast Cells physiology, Viscera
- Abstract
Introduction: Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver diseases. We administered Ketotifen, a mast cell stabilizer, and measured the mast cells in the splanchnic organs of cholestatic rats., Material and Methods: These groups were studied: sham-operated rats (S; n = 15), untreated microsurgical cholestasic rats (C; n = 20) and rats treated with Ketotifen: early (SK-e; n = 20 and CKe; n = 18), and late (SK-l; n = 15 and CK-l; n = 14)., Results: The cholestatic rats showed systemic and splanchnic impairments, such as ascites, portal hypertension, and biliary proliferation and fibrosis. The rats also showed a splanchnic increase of TNF-α, IL-1β and MCP-1, and a reduction of IL-4, IL-10 and antioxidants. An increase of VEGF in the ileum and mesenteric lymphatic complex was associated with a liver reduction of TGF-β1. Ketotifen reduces the degree of hepatic insufficiency and the splanchnic inflammatory mediators, as well as VEGF and TGF-ß1 levels. Ketotifen also reduces the connective tissue mast cells in the mesenteric lymphatic complex of cholestatic rats, while increases the hepatic mucosal mast cells., Conclusions: In cholestatic rats, Ketotifen improves liver function and ascites, and also reduces pro-inflammatory mediators in the splanchnic area. The decrease in connective tissue mast cells in the mesenteric lymphatic complex due to the administration of Ketotifen would lead to the improvement of the inflammatory splanchnic response, and consequently the abovementioned complications., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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133. TLR9 -1486C/T polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation.
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de la Fuente S, Citores MJ, Lucena JL, Muñoz P, and Cuervas-Mons V
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- Adult, Aged, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular surgery, Female, Humans, Liver Neoplasms metabolism, Liver Neoplasms surgery, Liver Transplantation, Male, Middle Aged, Neoplasm Recurrence, Local metabolism, Polymorphism, Single Nucleotide, Retrospective Studies, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics, Neoplasm Recurrence, Local genetics, Toll-Like Receptor 9 genetics
- Abstract
Aim: To determine whether TLR9 polymorphisms are associated with tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC). Patients & methods: All patients who underwent liver transplantation, and had viable HCC in the explanted liver were included. TLR9 -1237C/T and -1486C/T polymorphisms were analyzed by real-time PCR and melting curves analysis. Results: 20 of 159 patients (12.6%) developed post-transplant HCC recurrence. Tumors exceeding Milan criteria, moderately-to-poorly differentiated tumors and microvascular invasion on explants, and pretransplant α-fetoprotein level (all p < 0.01) were associated with an increased risk, while TLR9 -1486TT genotype was associated with a decreased risk of HCC recurrence (p = 0.03). Conclusion: TLR9 -1486C/T might help to preoperatively identify patients at low risk of post-transplant HCC recurrence.
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- 2019
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134. Benefits of hepatitis C cure with antivirals: why test and treat?
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Lledó G, Benítez-Gutiérrez L, Arias A, Requena S, Cuervas-Mons V, and de Mendoza C
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- Hepacivirus classification, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Liver Cirrhosis drug therapy, Liver Cirrhosis virology, Liver Neoplasms drug therapy, Liver Neoplasms virology, Antiviral Agents therapeutic use, Hepacivirus isolation & purification, Hepatitis C, Chronic drug therapy
- Abstract
Chronic hepatitis C virus (HCV) infection is one of the major causes of death worldwide due to infectious agents. The advent of direct-acting antivirals has dramatically improved the chance of HCV elimination, even for patients with decompensated cirrhosis. Along with HCV cure, benefits are recognized in terms of regression of liver fibrosis and risk of hepatocellular carcinoma. Furthermore, beyond hepatic outcomes, several extrahepatic benefits may result from sustained HCV eradication, including improvements in the neurocognitive function and reduced cardiovascular disease risk. Finally, there is no doubt that the individual success of direct-acting antivirals is largely contributing to halt HCV transmission globally, in the absence of an effective HCV prophylactic vaccine.
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- 2019
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135. Preface.
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Cuervas-Mons V and López-Hoyos M
- Published
- 2019
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136. Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation.
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Citores MJ, Lucena JL, de la Fuente S, and Cuervas-Mons V
- Abstract
Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT., Competing Interests: Conflict-of-interest statement: All of the authors declare no conflicts of interest related to this article.
- Published
- 2019
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137. Regression of liver fibrosis after curing chronic hepatitis C with oral antivirals in patients with and without HIV coinfection.
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Lledó GM, Carrasco I, Benítez-Gutiérrez LM, Arias A, Royuela A, Requena S, Cuervas-Mons V, and de Mendoza C
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- Elasticity Imaging Techniques, Female, HIV Infections complications, Humans, Liver pathology, Male, Middle Aged, Treatment Outcome, Antiviral Agents therapeutic use, Coinfection drug therapy, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Liver Cirrhosis pathology
- Abstract
Background: Treatment with direct-acting antivirals (DAA) eradicates hepatitis C virus (HCV) from most chronic carriers. Information on regression of liver fibrosis and the influence of HIV is scarce in cured patients., Methods: All consecutive HCV-infected individuals treated with DAA at our institution were examined. Hepatic elastography was performed at baseline and at the time of SVR12. Liver fibrosis regression was defined as a shift from advanced fibrosis (Metavir F3-F4) to null-mild fibrosis (F0-F2) and/or a reduction greater than 30% kPa. AST to platelet ratio index (APRI) and fibrosis 4 (FIB-4) scores were calculated in parallel., Results: A total of 260 patients were treated with DAA. All but 14 achieved SVR12 and represented the study population. HIV confection was present in 42%. At baseline, 57.2% had advanced liver fibrosis with a median of 11 kPa, FIB-4 of 2.4, and APRI of 0.95. At the time of SVR12, a median reduction of 2.1 kPa (P < 0.001) was recognized using elastography. A significant fibrosis regression was seen in 40%, being more frequent in patients with baseline advanced fibrosis than in those with null-mild fibrosis (52.3 vs. 22.5%; P < 0.001). Even so, 41.2% of patients with baseline F3-F4 kept within cirrhotic scores. In multivariable analysis, only baseline stiffness was significantly associated with the extent of liver fibrosis regression., Conclusion: HCV cure with DAA is associated with regression of liver fibrosis in most patients treated with DAA, as measured using elastography, FIB-4 and APRI. This benefit is more pronounced in patients with baseline advanced fibrosis and cirrhosis. The dynamics of liver fibrosis regression are not influenced by HIV coinfection.
- Published
- 2018
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138. Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study.
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Manzardo C, Londoño MC, Castells L, Testillano M, Luis Montero J, Peñafiel J, Subirana M, Moreno A, Aguilera V, Luisa González-Diéguez M, Calvo-Pulido J, Xiol X, Salcedo M, Cuervas-Mons V, Manuel Sousa J, Suarez F, Serrano T, Ignacio Herrero J, Jiménez M, Fernandez JR, Giménez C, Del Campo S, Esteban-Mur JI, Crespo G, Moreno A, de la Rosa G, Rimola A, and Miro JM
- Subjects
- Coinfection virology, Drug Therapy, Combination, Female, Follow-Up Studies, HIV Infections virology, Hepatitis C virology, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Recurrence, Transplant Recipients, Antiviral Agents therapeutic use, Coinfection drug therapy, HIV drug effects, HIV Infections drug therapy, Hepacivirus drug effects, Hepatitis C drug therapy, Liver Transplantation methods
- Abstract
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/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (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 12 weeks 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., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2018
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139. Prevalence and progression of chronic kidney disease after liver transplant: a prospective, real-life, observational, two-year multicenter study.
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Herrero JI, Cuervas-Mons V, Gómez-Bravo MÁ, Fabregat J, Otero A, Bilbao I, Salcedo MM, González-Diéguez ML, Fernández JR, Serrano MT, Jiménez M, Rodrigo JM, Narváez I, and Sánchez G
- Subjects
- Adult, Aged, Disease Progression, Female, Humans, Kidney Function Tests, Male, Middle Aged, Postoperative Complications epidemiology, Prevalence, Prospective Studies, Liver Transplantation, Renal Insufficiency, Chronic epidemiology
- Abstract
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 m2. The mean glomerular filtration rate increased from 72.3 to 75.6 ml/min/1.73 m2 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.
- Published
- 2018
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140. Baseline NS5A resistance associated substitutions may impair DAA response in real-world hepatitis C patients.
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Carrasco I, Arias A, Benítez-Gutiérrez L, Lledó G, Requena S, Cuesta M, Cuervas-Mons V, and de Mendoza C
- Subjects
- Adult, Aged, Amino Acid Substitution, Coinfection virology, Female, Genotype, HIV Infections virology, Hepacivirus drug effects, Hepacivirus genetics, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Treatment Outcome, Antiviral Agents therapeutic use, Drug Resistance, Viral genetics, Hepatitis C, Chronic drug therapy, Treatment Failure, Viral Nonstructural Proteins genetics
- Abstract
Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3-F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA-naïve HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
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141. Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.
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Aguado JM, Silva JT, Fernández-Ruiz M, Cordero E, Fortún J, Gudiol C, Martínez-Martínez L, Vidal E, Almenar L, Almirante B, Cantón R, Carratalá J, Caston JJ, Cercenado E, Cervera C, Cisneros JM, Crespo-Leiro MG, Cuervas-Mons V, Elizalde-Fernández J, Fariñas MC, Gavaldà J, Goyanes MJ, Gutiérrez-Gutiérrez B, Hernández D, Len O, López-Andujar R, López-Medrano F, Martín-Dávila P, Montejo M, Moreno A, Oliver A, Pascual A, Pérez-Nadales E, Román-Broto A, San-Juan R, Serón D, Solé-Jover A, Valerio M, Muñoz P, and Torre-Cisneros J
- Subjects
- Humans, Postoperative Complications, Anti-Bacterial Agents therapeutic use, Disease Management, Drug Resistance, Multiple, Gram-Negative Bacterial Infections drug therapy, Gram-Negative Bacterial Infections etiology, Gram-Negative Bacterial Infections microbiology, Organ Transplantation, Tissue Donors, Transplant Recipients
- Abstract
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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142. High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.
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Mariño Z, Pascasio-Acevedo JM, Gallego A, Diago M, Baliellas C, Morillas R, Prieto M, Moreno JM, Sánchez-Antolín G, Vergara M, Forné M, Fernández I, Castro MA, Pascual S, Gómez A, Castells L, Montero JL, Crespo J, Calleja JL, García-Samaniego J, Carrión JA, Arencibia AC, Blasco A, López-Núñez C, Sánchez-Ruano JJ, Gea-Rodríguez F, Giráldez Á, Cabezas J, Hontangas V, Torras X, Castellote J, Romero-Gómez M, Turnes J, de Artaza T, Narváez I, Cuervas-Mons V, and Forns X
- Subjects
- Adult, Aged, Aged, 80 and over, Drug Therapy, Combination, Female, Hepacivirus genetics, Hepatitis C genetics, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Hepatitis C drug therapy, Registries, Simeprevir therapeutic use, Sofosbuvir therapeutic use
- Abstract
Background and Aims: Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients., Methods: This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed., Results: Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×10
9 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%., Conclusions: In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2017
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143. Efficacy and safety of daclatasvir-based antiviral therapy in hepatitis C virus recurrence after liver transplantation. Role of cirrhosis and genotype 3. A multicenter cohort study.
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Salcedo M, Prieto M, Castells L, Pascasio JM, Montero Alvarez JL, Fernández I, Sánchez-Antolín G, González-Diéguez L, García-Gonzalez M, Otero A, Lorente S, Espinosa MD, Testillano M, González A, Castellote J, Casafont F, Londoño MC, Pons JA, Molina Pérez E, Cuervas-Mons V, Pascual S, Herrero JI, Narváez I, Vinaixa C, Llaneras J, Sousa JM, and Bañares R
- Subjects
- Adult, Aged, Aged, 80 and over, Carbamates, Female, Hepatitis C mortality, Hepatitis C virology, Humans, Immunosuppression Therapy, Male, Middle Aged, Pyrrolidines, Recurrence, Retrospective Studies, Spain epidemiology, Sustained Virologic Response, Valine analogs & derivatives, Antiviral Agents therapeutic use, Hepatitis C drug therapy, Imidazoles therapeutic use, Liver Transplantation, Postoperative Complications drug therapy
- Abstract
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., (© 2017 Steunstichting ESOT.)
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- 2017
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144. Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis.
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de la Fuente S, Citores MJ, Duca A, Cisneros E, Baños I, Vilches C, and Cuervas-Mons V
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular epidemiology, Female, Gene Frequency, Genotype, Genotyping Techniques, Hepatitis C, Chronic complications, Humans, Interferons, Liver Cirrhosis complications, Liver Cirrhosis epidemiology, Liver Neoplasms epidemiology, Male, Middle Aged, Polymorphism, Single Nucleotide, Retrospective Studies, Young Adult, Carcinoma, Hepatocellular genetics, Genetic Predisposition to Disease, Interleukins genetics, Liver Cirrhosis genetics, Liver Neoplasms genetics
- Abstract
Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11-17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42-3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03-3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5-4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02-1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24-5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.
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- 2017
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145. Preface.
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Sampaio S, Manfro RC, and Cuervas-Mons V
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- 2017
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146. Cardiovascular morbidity and mortality after liver transplantation: The protective role of mycophenolate mofetil.
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D'Avola D, Cuervas-Mons V, Martí J, Ortiz de Urbina J, Lladó L, Jimenez C, Otero E, Suarez F, Rodrigo JM, Gómez MA, Fraga E, Lopez P, Serrano MT, Rios A, Fábrega E, and Herrero JI
- Subjects
- Adult, Age Factors, Aged, Cardiovascular Diseases etiology, Cyclosporine adverse effects, Cyclosporine therapeutic use, Diabetes Mellitus, Type 1 complications, Dyslipidemias complications, End Stage Liver Disease surgery, Female, Follow-Up Studies, Graft Rejection prevention & control, Humans, Hypertension complications, Immunosuppressive Agents therapeutic use, Male, Metabolic Syndrome complications, Middle Aged, Postoperative Complications etiology, Prevalence, Prospective Studies, Risk Factors, Severity of Illness Index, Spain epidemiology, Survival Analysis, Tacrolimus adverse effects, Tacrolimus therapeutic use, Transplant Recipients, Cardiovascular Diseases epidemiology, Immunosuppressive Agents adverse effects, Liver Transplantation adverse effects, Mycophenolic Acid therapeutic use, Postoperative Complications epidemiology
- Abstract
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., (© 2017 by the American Association for the Study of Liver Diseases.)
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- 2017
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147. Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials.
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Arias A, Aguilera A, Soriano V, Benítez-Gutiérrez L, Lledó G, Navarro D, Treviño A, Otero E, Peña JM, Cuervas-Mons V, and de Mendoza C
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- Administration, Oral, Adult, Aged, Benzimidazoles therapeutic use, Coinfection, Female, Fluorenes therapeutic use, Genotype, HIV drug effects, HIV genetics, HIV isolation & purification, HIV Infections pathology, HIV Infections virology, Hepacivirus classification, Hepacivirus genetics, Hepacivirus isolation & purification, Hepatitis C, Chronic pathology, Hepatitis C, Chronic virology, Humans, Liver Cirrhosis pathology, Liver Cirrhosis virology, Male, Middle Aged, Prognosis, RNA, Viral antagonists & inhibitors, RNA, Viral metabolism, Recurrence, Ribavirin therapeutic use, Risk Factors, Sofosbuvir, Treatment Failure, Uridine Monophosphate analogs & derivatives, Uridine Monophosphate therapeutic use, Antiviral Agents therapeutic use, HIV Infections drug therapy, Hepacivirus drug effects, Hepatitis C, Chronic drug therapy, Liver Cirrhosis drug therapy, RNA, Viral genetics
- Abstract
Background: Cure rates above 90% have been reported in most Phase III clinical trials using distinct all-oral direct-acting antivirals (DAAs) in chronic hepatitis C patients. Preliminary results in real-world patients have confirmed this, although efficacy tends to be lower., Methods: All consecutive chronic hepatitis C patients treated with all-oral DAA regimens at three hepatitis clinics in Spain were retrospectively examined. Host and viral factors were tested as predictors of treatment failure., Results: A total of 363 chronic hepatitis C patients had completed a course of all-oral DAA therapy outside clinical trials up to the end of 2015. All but 14 (4%) patients achieved sustained virological response. There were 10 failures that occurred after 12 weeks of sofosbuvir-ledipasvir, despite 5 of them being on ribavirin. All failures but one were relapses. The only patient with viral breakthrough selected NS5B L159F and NS5A Y93H. In multivariate analyses, only advanced liver fibrosis (Metavir F3-F4) and HIV coinfection were significantly associated with treatment failure. A trend towards lower response was seen for HCV genotype 4., Conclusions: Treatment failures outside clinical trials are roughly seen in 4% of chronic hepatitis C patients who complete a course of all-oral DAA therapy, resembling what is seen in registration trials. In our series, outcomes were not significantly influenced by ribavirin addition, IL28B polymorphisms, HCV genotype, high baseline HCV RNA or prior interferon failure. However, advanced liver fibrosis and HIV coinfection were significantly associated with treatment failure. Our findings support that there is still room for individualization of current DAA therapy.
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- 2017
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148. Impact of ITPA gene polymorphisms on the risk of ribavirin-induced haemolytic anaemia using interferon-free antivirals for chronic hepatitis C.
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Esposito I, Benítez-Gutiérrez L, Treviño A, Arias A, Citores MJ, Requena S, Soriano V, Cuervas-Mons V, and de Mendoza C
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- Adult, Aged, Alleles, Antiviral Agents therapeutic use, Female, Genotype, Hepatitis C, Chronic drug therapy, Humans, Male, Middle Aged, Retrospective Studies, Ribavirin therapeutic use, Anemia, Hemolytic etiology, Antiviral Agents adverse effects, Disease Susceptibility, Hepatitis C, Chronic complications, Polymorphism, Single Nucleotide, Pyrophosphatases genetics, Ribavirin adverse effects
- Abstract
Background: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with haemolytic anaemia in chronic hepatitis C patients treated with pegylated interferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce., Methods: Median haemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic., Results: Median Hb drop in 55 patients was greater in rs1127354-CC than -CA/AA (1.8 versus 0.7 g/dl; P=0.029), and in rs6051702-AA than -AC/CC carriers (2.2 versus 1.1 g/dl; P=0.016). Eleven (20%) patients experienced severe anaemia, defined as Hb drop >3 g/dl or to <10 g/dl. All of them were rs6051702-AA., Conclusions: Baseline testing of rs6051702 may identify the subset of patients at greatest risk for RBV-induced anaemia using interferon-free hepatitis C therapies.
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- 2017
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149. Prevalence and outcome of portal thrombosis in a cohort of cirrhotic patients undergoing liver transplantation.
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Hernández Conde M, Llop Herrera E, de la Revilla Negro J, Pons Renedo F, Fernández Puga N, Martínez Porras JL, Trapero Marugan M, Cuervas-Mons V, Sánchez Turrión V, and Calleja Panero JL
- Subjects
- Adult, Aged, Cohort Studies, Female, Humans, Male, Middle Aged, Portal Vein, Prevalence, Retrospective Studies, Treatment Outcome, Young Adult, Liver Cirrhosis complications, Liver Cirrhosis surgery, Liver Transplantation adverse effects, Venous Thrombosis epidemiology, Venous Thrombosis therapy
- Abstract
Introduction: The prevalence of portal vein thrombosis (PVT) in patients that have undergone liver transplantation (LT) is 9.7% (SD 4.5). The aim of our study was to determine the prevalence, assess the factors that are associated with PVT and clarify their association with prognosis in patients with liver cirrhosis (LC) and LT., Aims and Methods: From 2005 to 2014, laboratory, radiological and surgical data were collected from patients with LC in our center who had undergone LT for the first time., Results: One hundred and ninety-one patients were included. The mean age was 55 (SD 9), 75.4% of patients were male and 48.7% had HCV. The Child-Pugh scores were A/B/C 41.9%/35.9%/25.5% and the MELD score was 15 (SD 6). Previous decompensations were: ascites (61.4%), hepatic encephalopathy (34.4%), variceal bleeding (25.4%), hepatocellular carcinoma (48.9%) and spontaneous bacterial peritonitis (SPB) (14.3%). The mean post-transplant follow-up was 42 months (0-113). PVT was diagnosed at LT in 18 patients (9.4%). Six patients were previously diagnosed using imaging tests (33.3%): 2 patients (11.1%) by DU and 4 patients (22.2%) by CT scan. All patients with PVT had DU in a mean time of 6 months before LT (0-44) and 90 patients (47.1%) had a CT scan in a median time of 6 months before LT (0-45). PVT was significantly related to the presence of SBP (33.3% vs 12.6%; p = 0.02) and lower levels of albumin (3.1g/dl vs 3.4g/dl; p = 0.05). MELD was higher in patients with PVT (16.6 vs 14.9; p = 0.3). There were no significant differences with regard to the need for transfusion of blood components. Moreover, the surgery time was similar in both groups. PVT correlated with a higher mortality in the first 30 days (8.8% vs 16.7%; p = 0.2)., Conclusion: Prior history of SBP and lower levels of albumin were identified as factors associated with PVT. The pre-transplant diagnosis rate is very low and the presence of PVT may have implications for short-term mortality.
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- 2016
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150. Preface.
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Cuervas-Mons V and López-Hoyos M
- Published
- 2016
- Full Text
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