Admission Serum Metabolites and Thyroxine Predict Advanced Hepatic Encephalopathy in a Multicenter Inpatient Cirrhosis Cohort.
Clin Gastroenterol Hepatol
; 21(4): 1031-1040.e3, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-35436625
ABSTRACT
BACKGROUND & AIMS:
Grades 3 to 4 hepatic encephalopathy (advanced HE), also termed brain failure, is an organ failure that defines acute-on-chronic liver failure. It is associated with poor outcomes in cirrhosis but cannot be predicted accurately. We aimed to determine the admission metabolomic biomarkers able to predict the development of advanced HE with subsequent validation.METHODS:
Prospective inpatient cirrhosis cohorts (multicenter and 2-center validation) without brain failure underwent admission serum collection and inpatient follow-up evaluation. Serum metabolomics were analyzed to predict brain failure on random forest analysis and logistic regression. A separate validation cohort also was recruited.RESULTS:
The multicenter cohort included 602 patients, of whom 144 developed brain failure (105 only brain failure) 3 days after admission. Unadjusted random forest analysis showed that higher admission microbially derived metabolites and lower isoleucine, thyroxine, and lysophospholipids were associated with brain failure development (area under the curve, 0.87 all; 0.90 brain failure only). Logistic regression area under the curve with only clinical variables significantly improved with metabolites (95% CI 0.65-0.75; P = .005). Four metabolites that significantly added to brain failure prediction were low thyroxine and maltose and high methyl-4-hydroxybenzoate sulfate and 3-4 dihydroxy butyrate. Thyroxine alone also significantly added to the model (P = .05). The validation cohort including 81 prospectively enrolled patients, of whom 11 developed brain failure. Admission hospital laboratory thyroxine levels predicted brain failure development despite controlling for clinical variables with high specificity.CONCLUSIONS:
In a multicenter inpatient cohort, admission serum metabolites, including thyroxine, predicted advanced HE development independent of clinical factors. Admission low local laboratory thyroxine levels were validated as a predictor of advanced HE development in a separate cohort.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encefalopatia Hepática
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Gastroenterol Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2023
Tipo de documento:
Article