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dc.creatorTranah, Thomas H.es
dc.creatorBallester, María Pilares
dc.creatorCarbonell-Asins, Juan Antonioes
dc.creatorAmpuero Herrojo, Javieres
dc.creatorAlexandrino, Gonçaloes
dc.creatorCaracostea, Andraes
dc.creatorRomero Gómez, Manueles
dc.creatorShawcross, Debbie L.es
dc.date.accessioned2023-05-29T15:54:37Z
dc.date.available2023-05-29T15:54:37Z
dc.date.issued2022-07-22
dc.identifier.citationTranah, T.H., Ballester, M.P., Carbonell-Asins, J.A., Ampuero Herrojo, J., Alexandrino, G., Caracostea, A.,...,Shawcross, D.L. (2022). Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis. Journal of Hepatology, 77 (6), 1554-1563. https://doi.org/10.1016/j.jhep.2022.07.014.
dc.identifier.issn1600-0641; 0168-8278es
dc.identifier.urihttps://hdl.handle.net/11441/146758
dc.description.abstractBackground & Aims Hyperammonaemia is central in the pathogenesis of hepatic encephalopathy. It also has pleiotropic deleterious effects on several organ systems, such as immune function, sarcopenia, energy metabolism and portal hypertension. This study was performed to test the hypothesis that severity of hyperammonaemia is a risk factor for liver-related complications in clinically stable outpatients with cirrhosis. Methods We studied 754 clinically stable outpatients with cirrhosis from 3 independent liver units. Baseline ammonia levels were corrected to the upper limit of normal (AMM-ULN) for the reference laboratory. The primary endpoint was hospitalisation with liver-related complications (a composite endpoint of bacterial infection, variceal bleeding, overt hepatic encephalopathy, or new onset or worsening of ascites). Multivariable competing risk frailty analyses using fast unified random forests were performed to predict complications and mortality. External validation was carried out using prospective data from 130 patients with cirrhosis in an independent tertiary liver centre. Results Overall, 260 (35%) patients were hospitalised with liver-related complications. On multivariable analysis, AMM-ULN was an independent predictor of both liver-related complications (hazard ratio 2.13; 95% CI 1.89–2.40; p <0.001) and mortality (hazard ratio 1.45; 95% CI 1.20–1.76; p <0.001). The AUROC of AMM-ULN was 77.9% for 1-year liver-related complications, which is higher than traditional severity scores. Statistical differences in survival were found between high and low levels of AMM-ULN both for complications and mortality (p <0.001) using 1.4 as the optimal cut-off from the training set. AMM-ULN remained a key variable for the prediction of complications within the random forests model in the derivation cohort and upon external validation. Conclusion Ammonia is an independent predictor of hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis and performs better than traditional prognostic scores in predicting complications. Lay summary We conducted a prospective cohort study evaluating the association of blood ammonia levels with the risk of adverse outcomes in 754 patients with stable cirrhosis across 3 independent liver units. We found that ammonia is a key determinant that helps to predict which patients will be hospitalised, develop liver-related complications and die; this was confirmed in an independent cohort of patients.es
dc.formatapplication/pdfes
dc.format.extent11 p.es
dc.language.isoenges
dc.publisherElsevieres
dc.relation.ispartofJournal of Hepatology, 77 (6), 1554-1563.
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titlePlasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosises
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0168827822029476?via%3Dihubes
dc.identifier.doi10.1016/j.jhep.2022.07.014es
dc.journaltitleJournal of Hepatologyes
dc.publication.volumen77es
dc.publication.issue6es
dc.publication.initialPage1554es
dc.publication.endPage1563es

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