Liver status and outcomes in patients without previous known liver disease receiving anticoagulant therapy for venous thromboembolism

Diego Martínez-Urbistondo, Rocío G de la Garza, Paula Villares-Fernández, Carme Font, Sebastian Schellong, Juan José López-Núñez, Aída Gil-Díaz, María Del Carmen Díaz-Pedroche, Jana Hirmerova, Manuel Monreal, RIETE Investigators, M D Adarraga, J Aibar, J Alonso, C Amado, J I Arcelus, A Asuero, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón-Andrés, A Blanco-Molina, F Beddar Chaib, E Botella, J Castro, L Chasco, J Criado, C de Ancos, J Del Toro, P Demelo-Rodríguez, A M Díaz-Brasero, M C Díaz-Pedroche, J A Díaz-Peromingo, M V Di Campli, A Dubois-Silva, J C Escribano, F Espósito, A I Farfán-Sedano, C Fernández-Capitán, J L Fernández-Reyes, M A Fidalgo, K Flores, C Font, L Font, I Francisco, C Gabara, F Galeano-Valle, M A García, F García-Bragado, M García de Herreros, R G de la Garza, C García-Díaz, A Gil-Díaz, C Gómez-Cuervo, E Grau, L Guirado, J Gutiérrez, L Hernández-Blasco, L Jara-Palomares, M J Jaras, D Jiménez, R Jiménez, C Jiménez-Alfaro, M D Joya, S Lainez-Justo, A Lalueza, A Latorre, J Lima, J L Lobo, L López-Jiménez, P López-Miguel, J J López-Núñez, R López-Reyes, J B López-Sáez, A Lorenzo, O Madridano, A Maestre, P J Marchena, M Martín Del Pozo, F Martín-Martos, D Martínez-Urbistondo, C Mella, M I Mercado, J Moisés, M Monreal, A Muñoz-Blanco, J A Nieto, E Nofuentes-Pérez, M J Núñez-Fernández, M Olid-Velilla, M C Olivares, J Osorio, S Otalora, R Otero, D Paredes, J M Pedrajas, J A Porras, J Portillo, I Redondo, C Rodríguez-Matute, V Rosa, P Ruiz-Artacho, J Ruiz-Ruiz, G Salgueiro, R Sánchez-Martínez, J F Sánchez-Muñoz-Torrero, T Sancho, S Soler, B Suárez-Rodríguez, J M Suriñach, M I Torres, A Torres-Sánchez, C Tolosa, J Trujillo-Santos, F Uresandi, B Valero, R Valle, J F Varona, L Vela, J R Vela, G Vidal, A Villalobos, P Villares, C Zamora, C Ay, S Nopp, I Pabinger, M M Engelen, T Vanassche, P Verhamme, J Hirmerova, R Malý, S Accassat, N Ait Abdallah, L Bertoletti, A Bura-Riviere, J Catella, F Couturaud, B Crichi, P Debourdeau, O Espitia, D Farge-Bancel, C Grange, H Helfer, K Lacut, R Le Mao, I Mahé, P Morange, F Moustafa, G Poenou, G Sarlon-Bartoli, P Suchon, I Quere, S Schellong, A Braester, B Brenner, G Kenet, I Tzoran, M Basaglia, F Bilora, C Bortoluzzi, B Brandolin, M Ciammaichella, A De Angelis, P Di Micco, E Imbalzano, S Merla, R Pesavento, P Prandoni, C Siniscalchi, A Tufano, A Visonà, N Vo Hong, B Zalunardo, Y Nishimoto, Y Sato, K Make, A Skride, S Strautmane, S Fonseca, F Martins, J Meireles, M Bosevski, H Bounameaux, L Mazzolai, J A Caprini, H M Bui, Diego Martínez-Urbistondo, Rocío G de la Garza, Paula Villares-Fernández, Carme Font, Sebastian Schellong, Juan José López-Núñez, Aída Gil-Díaz, María Del Carmen Díaz-Pedroche, Jana Hirmerova, Manuel Monreal, RIETE Investigators, M D Adarraga, J Aibar, J Alonso, C Amado, J I Arcelus, A Asuero, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón-Andrés, A Blanco-Molina, F Beddar Chaib, E Botella, J Castro, L Chasco, J Criado, C de Ancos, J Del Toro, P Demelo-Rodríguez, A M Díaz-Brasero, M C Díaz-Pedroche, J A Díaz-Peromingo, M V Di Campli, A Dubois-Silva, J C Escribano, F Espósito, A I Farfán-Sedano, C Fernández-Capitán, J L Fernández-Reyes, M A Fidalgo, K Flores, C Font, L Font, I Francisco, C Gabara, F Galeano-Valle, M A García, F García-Bragado, M García de Herreros, R G de la Garza, C García-Díaz, A Gil-Díaz, C Gómez-Cuervo, E Grau, L Guirado, J Gutiérrez, L Hernández-Blasco, L Jara-Palomares, M J Jaras, D Jiménez, R Jiménez, C Jiménez-Alfaro, M D Joya, S Lainez-Justo, A Lalueza, A Latorre, J Lima, J L Lobo, L López-Jiménez, P López-Miguel, J J López-Núñez, R López-Reyes, J B López-Sáez, A Lorenzo, O Madridano, A Maestre, P J Marchena, M Martín Del Pozo, F Martín-Martos, D Martínez-Urbistondo, C Mella, M I Mercado, J Moisés, M Monreal, A Muñoz-Blanco, J A Nieto, E Nofuentes-Pérez, M J Núñez-Fernández, M Olid-Velilla, M C Olivares, J Osorio, S Otalora, R Otero, D Paredes, J M Pedrajas, J A Porras, J Portillo, I Redondo, C Rodríguez-Matute, V Rosa, P Ruiz-Artacho, J Ruiz-Ruiz, G Salgueiro, R Sánchez-Martínez, J F Sánchez-Muñoz-Torrero, T Sancho, S Soler, B Suárez-Rodríguez, J M Suriñach, M I Torres, A Torres-Sánchez, C Tolosa, J Trujillo-Santos, F Uresandi, B Valero, R Valle, J F Varona, L Vela, J R Vela, G Vidal, A Villalobos, P Villares, C Zamora, C Ay, S Nopp, I Pabinger, M M Engelen, T Vanassche, P Verhamme, J Hirmerova, R Malý, S Accassat, N Ait Abdallah, L Bertoletti, A Bura-Riviere, J Catella, F Couturaud, B Crichi, P Debourdeau, O Espitia, D Farge-Bancel, C Grange, H Helfer, K Lacut, R Le Mao, I Mahé, P Morange, F Moustafa, G Poenou, G Sarlon-Bartoli, P Suchon, I Quere, S Schellong, A Braester, B Brenner, G Kenet, I Tzoran, M Basaglia, F Bilora, C Bortoluzzi, B Brandolin, M Ciammaichella, A De Angelis, P Di Micco, E Imbalzano, S Merla, R Pesavento, P Prandoni, C Siniscalchi, A Tufano, A Visonà, N Vo Hong, B Zalunardo, Y Nishimoto, Y Sato, K Make, A Skride, S Strautmane, S Fonseca, F Martins, J Meireles, M Bosevski, H Bounameaux, L Mazzolai, J A Caprini, H M Bui

Abstract

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10-2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04-2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation.

Trial registration: ClinicalTrials.gov NCT02832245.

Keywords: Anticoagulation adverse events; Clinical VTE; Healthy individuals; Non-invasive liver assessment; VTE risk assessment.

Conflict of interest statement

All the authors Diego Martínez-Urbistondo, Rocío G de la Garza, Paula Villares-Fernández, Carme Font, Sebastian Schellong, Juan José López-Núñez Aída Gil-Díaz, María del Carmen Díaz-Pedroche, Jana Hirmerova and Manuel Monreal declare no conflicts of interest.

© 2021. Società Italiana di Medicina Interna (SIMI).

Figures

Fig. 1
Fig. 1
Flow chart of selection of patients for final analysis
Fig. 2
Fig. 2
Adjusted Cox regression analysis for all-cause mortality during anticoagulation, according to elevated vs. normal liver enzymes
Fig. 3
Fig. 3
Adjusted Cox regression analysis for major bleeding during anticoagulation according to risk for liver fibrosis

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