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Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis

Ballester, Maria Pilar; Tranah, Thomas H; Balcar, Lorenz; Fiorillo, Alessandra; Ampuero, Javier; Kerbert, Annarein JC; Thomsen, Karen L; ... Jalan, Rajiv; + view all (2023) Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis. Journal of Hepatology , 79 (4) pp. 967-976. 10.1016/j.jhep.2023.05.022.

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Abstract

BACKGROUND AND AIMS: Neuropsychological and psychophysical tests are recommended for the risk assessment for overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. This study aimed to determine the role of neuropsychological or psychophysical tests and ammonia and to develop the AMMON-OHE model for risk stratification regarding subsequent OHE development in outpatients with cirrhosis.// METHODS: This observational, prospective study included 426 outpatients without previous OHE from 3 liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk analyses and random survival forest were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units. // RESULTS: Significant differences were found in time-to-OHE (log-rank p<0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (HR: 4.4; 95% CI: 2.4-8.1, p<0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor for development of OHE (HR: 1.4; 95%CI: 1.1-1.9; p=0.015). The AMMON-OHE model included sex, diabetes, albumin, creatinine and AMM-ULN, and showed a C-index of 0.844 and 0.728 in the two external validation cohorts. // CONCLUSIONS: This study developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at highest risk for developing a first episode of OHE.

Type: Article
Title: Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis
Location: Netherlands
DOI: 10.1016/j.jhep.2023.05.022
Publisher version: https://doi.org/10.1016/j.jhep.2023.05.022
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Ammonia, Cirrhosis, Critical flicker frequency, Overt hepatic encephalopathy, Psychometric hepatic encephalopathy score
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10171989
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