Elevación de los niveles de transaminasas y bilirrubina total como marcadores pronósticos de mortalidad en adultos hospitalizados por COVID-19. Un estudio de cohorte
DOI:
https://doi.org/10.52787/agl.v54i1.390Palabras clave:
COVID-19, mortalidad, pruebas de función hepática, transaminasas, bilirrubina, pronósticoResumen
Introducción. El hígado es un órgano que se ve afectado por múltiples mecanismos en presencia de COVID-19. El objetivo de este estudio fue determinar si los niveles elevados de alanina aminotransferasa, aspartato aminotransferasa y bilirrubina total son predictores de mortalidad en adultos con COVID-19.
Materiales y métodos. Estudio de cohorte retrospectivo de adultos hospitalizados entre 2020 y 2022 en un hospital universitario de Bogotá por COVID-19 e hipoxemia. La mortalidad por todas las causas fue el resultado primario. Y se construyó un modelo multivariado independiente para cada uno de los siguientes marcadores de lesión hepática: alanina aminotransferasa, aspartato aminotransferasa y bilirrubina total. Cada modelo se ajustó por edad, presencia de diabetes mellitus, presencia de fiebre durante la hospitalización, recuento de linfocitos, dímero D y lactato deshidrogenasa.
Resultados. Se incluyó a un total de 704 pacientes. La tasa de mortalidad fue del 38%. Los niveles elevados de alanina aminotransferasa, aspartato aminotransferasa y bilirrubina total al ingreso se registraron en el 64%, 64% y 8,3% de los pacientes, respectivamente. Según el análisis multivariado, la elevación de los niveles de aspartato aminotrasferasa (OR = 1.06; IC 95%: 1.02 - 1.11 por cada aumento de 40 U/L, valor de p = 0.009) y de bilirrubina total (OR = 1.26, IC 95%: 1.08 -1.47 por cada aumento de 1mg/dl, valor de p = 0.003) se asociaron de forma independiente con la muerte. El nivel de bilirrubina total también se asoció con el ingreso en la unidad de cuidados intensivos, la necesidad de ventilación mecánica invasiva y la duración de la estancia hospitalaria. Los resultados de la alanina aminotransferasa no permitieron concluir una asociación independiente con la muerte. La edad, la fiebre y el recuento más bajo de linfocitos durante la hospitalización también se asociaron con la muerte.
Conclusión. Los niveles elevados de transaminasas y bilirrubina total son hallazgos frecuentes en pacientes con COVID-19 e hipoxemia. La aspartato aminotransferasa y la bilirrubina total fueron predictoras de mortalidad en estos pacientes, por lo que su medición al ingreso es una práctica razonable. Es necesario avanzar en la incorporación de estos marcadores en modelos predictivos de mortalidad y en reglas de decisión clínica.
Citas
-1. Haldane V, De Foo C, Abdalla SM, Jung AS, Tan M, Wu S, et al. Health systems resilience in managing the COVID-19 pandemic: lessons from 28 countries. Nat Med. 2021 May 17; 27(6):964-80. Available from: https://www.nature.com/articles/s41591-021-01381-y
-2. Burn E, Tebé C, Fernandez-Bertolin S, Aragon M, Recalde M, Roel E, et al. The natural history of symptomatic COVID-19 during the first wave in Catalonia. Nat Commun. 2021 Feb 3;12 (1). Available from: https://pubmed.ncbi.nlm.nih.gov/33536436/
-3. Hundt MA, Deng Y, Ciarleglio MM, Nathanson MH, Lim JK. Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network. Hepatology. 2020 Oct;72(4). Available from: https://pubmed.ncbi.nlm.nih.gov/32725890/
-4. Berenguer J, Ryan P, Rodríguez-Baño J, Jarrín I, Carratalà J, Pachón J, et al. Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain. Clin Microbiol Infect. 2020 Nov;26(11). Available from: https://pubmed.ncbi.nlm.nih.gov/32758659/
-5. Marjot T, Webb GJ, Barritt AS, Moon AM, Stamataki Z, Wong VW, et al. COVID-19 and liver disease: mechanistic and clinical perspectives. Nat Rev Gastroenterol Hepatol. 2021 May;18(5). Available from: https://pubmed.ncbi.nlm.nih.gov/33692570/
-6. Halina Cichoż-Lach AM. Liver injury in the era of COVID-19. World J Gastroenterol. 2021 Feb 7;27(5):377. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856845/
-7. Hundt MA, Deng Y, Ciarleglio MM, Nathanson MH, Lim JK. Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network. Hepatology. 2020 Oct;72(4). Available from: https://pubmed.ncbi.nlm.nih.gov/32725890/
-8. Ma GG, Shen YX, Wu L, Luo Z, Zhu CW, Chen SY, et al. Effect of liver injury on prognosis and treatment of hospitalized patients with COVID-19 pneumonia. Annals of translational medicine. 2021 Jan;9(1). Available from: https://pubmed.ncbi.nlm.nih.gov/33553303/
-9. Zhang L, Hou J, Ma FZ, Li J, Xue S, Xu ZG. The common risk factors for progression and mortality in COVID-19 patients: a meta-analysis. Arch Virol;1. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017903/
-10. Hundt MA, Deng Y, Ciarleglio MM, Nathanson MH, Lim JK. Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network. Hepatology. 2020 Oct;72(4). Available from: https://pubmed.ncbi.nlm.nih.gov/32725890/
-11. Gutiérrez HA. Estrategias de muestreo: diseño de encuestas y estimación de parámetros. Facultad de Estadística, Universidad Santo Tomás; 2009. Available from: https://books.google.com/books/about/Estrategias_de_muestreo.html?id=AXrUswEACAAJ
-12. Textor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT. Robust causal inference using directed acyclic graphs: the R package “dagitty.” Int J Epidemiol. 2016 Dec 1;45(6). Available from: https://pubmed.ncbi.nlm.nih.gov/28089956/
-13. Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J Epidemiol. 2020 Dec;35(12). Available from: https://pubmed.ncbi.nlm.nih.gov/33289900/
-14. Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr. 2020 Jul;14(4). Available from: https://pubmed.ncbi.nlm.nih.gov/32408118/
-15. Schlesinger S, Neuenschwander M, Lang A, Pafili K, Kuss O, Herder C, et al. Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis. Diabetologia. 2021 Jul; 64(7). Available from: https://pubmed.ncbi.nlm.nih.gov/33907860/
-16. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13). Available from: https://pubmed.ncbi.nlm.nih.gov/32091533/
-17. Tharakan S, Nomoto K, Miyashita S, Ishikawa K. Body temperature correlates with mortality in COVID-19 patients. Crit Care. 2020 Jun 5;24(1). Available from: https://pubmed.ncbi.nlm.nih.gov/32503659/
-18. Choron RL, Butts CA, Bargoud C, Krumrei NJ, Teichman AL, Schroeder ME, et al. Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients. J Intensive Care Med. 2021 Apr;36(4). Available from: https://pubmed.ncbi.nlm.nih.gov/33317374/
-19. Henry B, Cheruiyot I, Vikse J, Mutua V, Kipkorir V, Benoit J, et al. Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis. Acta Biomed. 2020 Sep 7;91(3). Available from: https://pubmed.ncbi.nlm.nih.gov/32921706/
-20. Melo AKG, Milby KM, Alma C, Acpn P, Santos RRP, Rocha AP, et al. Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis. PLoS One. 2021 Jun 29;16(6). Available from: https://pubmed.ncbi.nlm.nih.gov/34185801/
-21. Zhang L, Hou J, Ma FZ, Li J, Xue S, Xu ZG. The common risk factors for progression and mortality in COVID-19 patients: a meta-analysis. Arch Virol;1. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017903/
-22. Gungor B, Atici A, Baycan OF, Alici G, Ozturk F, Tugrul S, et al. Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: A systematic review and meta-analysis. Am J Emerg Med. 2021 Jan;39. Available from: https://pubmed.ncbi.nlm.nih.gov/33069541/
-23. Henry BM, Aggarwal G, Wong J, Benoit S, Vikse J, Plebani M, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis. Am J Emerg Med. 2020 Sep;38(9). Available from: https://pubmed.ncbi.nlm.nih.gov/32738466/
-24. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Ann Intern Med. 2007 Oct 16;147(8). Available from: https://pubmed.ncbi.nlm.nih.gov/17938389/
-25. Cho J, Lee J, Sia CH, Koo CS, Tan BY, Hong W, et al. Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus 2 infection: a systematic review. Singapore Med J. 2021 Sep 21; Available from: https://pubmed.ncbi.nlm.nih.gov/34544216/
-26. Bzeizi K, Abdulla M, Mohammed N, Alqamish J, Jamshidi N, Broering D. Effect of COVID-19 on liver abnormalities: a systematic review and meta-analysis. Sci Rep. 2021 May 19;11(1). Available from: https://pubmed.ncbi.nlm.nih.gov/34012016/
-27. Chen Z, Peng Y, Wu X, Pang B, Yang F, Zheng W, et al. Comorbidities and complications of COVID-19 associated with disease severity, progression, and mortality in China with centralized isolation and hospitalization: A systematic review and meta-analysis. Frontiers in public health. 2022 Aug 16;10. Available from: https://pubmed.ncbi.nlm.nih.gov/36052001/
-28. Laali A, Tabibzadeh A, Esghaei M, Yousefi P, Soltani S, Ajdarkosh H, et al. Liver Function Tests Profile in COVID-19 Patients at the Admission Time: A Systematic Review of Literature and Conducted Researches. Adv Biomed Res. 2020 Dec 23;9. Available from: https://pubmed.ncbi.nlm.nih.gov/33912490/
-29. Cattelan AM, Di Meco E, Trevenzoli M, Frater A, Ferrari A, Villano M, et al. Clinical characteristics and laboratory biomarkers changes in COVID-19 patients requiring or not intensive or sub-intensive care: a comparative study. BMC Infect Dis. 2020 Dec 9;20(1). Available from: https://pubmed.ncbi.nlm.nih.gov/33297986/
-30. Snipelisky D, Johnson R, Prasad R, Lakhani B, Ellington J. Characteristics and Outcomes Based on Perceived Illness Severity in SARS-CoV-2. South Med J. 2020 Dec;113(12). Available from: https://pubmed.ncbi.nlm.nih.gov/33263129/
-31. Galiero R, Pafundi PC, Simeon V, Rinaldi L, Perrella A, Vetrano E, et al. Impact of chronic liver disease upon admission on COVID-19 in-hospital mortality: Findings from COVOCA study. PLoS One. 2020 Dec 10;15(12). Available from: https://pubmed.ncbi.nlm.nih.gov/33301529/
-32. Radivojevic A, Aa AJ, Ravanavena A, Ravindra C, Igweonu-Nwakile EO, Ali S, et al. A Systematic Review of SARS-CoV-2-Associated Hepatic Dysfunction and the Impact on the Clinical Outcome of COVID-19. Cureus. 2022 Jul 14;14(7). Available from: https://pubmed.ncbi.nlm.nih.gov/35974857/
-33. Cao B, Jing X, Liu Y, Wen R, Wang C. Comparison of laboratory parameters in mild vs. severe cases and died vs. survived patients with COVID-19: systematic review and meta-analysis. J Thorac Dis. 2022 May;14(5). Available from: https://pubmed.ncbi.nlm.nih.gov/35693606/
-34. Harapan H, Fajar JK, Supriono S, Soegiarto G, Wulandari L, Seratin F, et al. The prevalence, predictors and outcomes of acute liver injury among patients with COVID-19: A systematic review and meta-analysis. Rev Med Virol. 2022 May;32(3). Available from: https://pubmed.ncbi.nlm.nih.gov/34643006/
-35. Mohammed SA, Eid KM, Anyiam FE, Wadaaallah H, Muhamed MAM, Morsi MH, et al. Liver injury with COVID-19: laboratory and histopathological outcome-systematic review and meta-analysis. Egyptian liver journal. 2022;12(1). Available from: https://pubmed.ncbi.nlm.nih.gov/35096428/
-36. Sotgia S, Mangoni AA, Mellino S, Cangemi M, Paliogiannis P, Fois AG, et al. A meta-regression study of the clinical significance of serum aminotransferases in COVID-19. Eur Rev Med Pharmacol Sci. 2021 Nov;25(21). Available from: https://pubmed.ncbi.nlm.nih.gov/34787885/
-37. Zahedi M, Yousefi M, Abounoori M, Malekan M, Tajik F, Heydari K, et al. The Interrelationship between Liver Function Test and the Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. Iran J Med Sci. 2021 Jul;46(4). Available from: https://pubmed.ncbi.nlm.nih.gov/34305236/
-38. Kariyawasam JC, Jayarajah U, Abeysuriya V, Riza R, Seneviratne SL. Involvement of the Liver in COVID-19: A Systematic Review. Am J Trop Med Hyg. 2022 Feb 24;106(4). Available from: https://pubmed.ncbi.nlm.nih.gov/35203056/
-39. Morris AH, Ioannidis JPA. Limitations of Medical Research and Evidence at the Patient-Clinician Encounter Scale. Chest. 2013 Apr;143(4):1127. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616682/
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2024 Andrés Fernando Rodríguez-Gutiérrez, Camilo Andrés Duarte-Calderón, Sergio Mauricio Moreno López
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.
