The occurrence of overt hepatic encephalopathy (OHE) in cirrhosis patients leads to a decrease in their health-related quality of life, along with a significant increase in the risk of hospitalization and death. At the 58th Annual Meeting of the European Association for the Study of the Liver (EASL 2023) and the EASL Congress 2023, Dr. María Pilar Ballester and her team from the Clinical Hospital of the University of Valencia in Spain introduced a new model for assessing the risk of OHE in outpatient cirrhosis patients – the AMMON-OHE model, which can effectively predict the risk of the first episode of OHE. Dr Huiguo Ding’s team from Capital Medical University Affiliated Beijing You’an Hospital, invited by Hepatology Digest, reviewed this research for readers to learn and reference.
Introduction to the Study
Minimal hepatic encephalopathy (MHE) is considered one of the clinical conditions that predispose to OHE and can occur in 80% of stable cirrhosis patients. The diagnosis of MHE is currently based on abnormalities in neurophysiological, neuropsychological, or psychophysical tests, and the results of these tests can be used to predict the risk of future overt hepatic encephalopathy and related mortality. Therefore, the European Association for the Study of the Liver (EASL) recommends that cirrhosis patients should undergo at least two (EASL) or one (AASLD) relevant test to assess the presence of MHE. However, the accuracy of neuropsychological and psychophysical tests recommended for risk assessment of overt hepatic encephalopathy is limited. High blood ammonia levels are a core pathogenic mechanism of hepatic encephalopathy, but their efficacy in predicting the occurrence of hepatic encephalopathy is unclear. This study aimed to determine the predictive roles of neuropsychological or psychophysical tests and blood ammonia and to develop the AMMON-OHE model for assessing the risk of subsequent overt hepatic encephalopathy in outpatient cirrhosis patients.
Ballester MP and colleagues prospectively observed data from 426 outpatient cirrhosis patients who were followed up for a median of 2.5 years from three different liver centers. Abnormalities in psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 were considered. Blood ammonia abnormalities were defined as above the upper limit of the respective laboratory reference range (AMM-ULN). The AMMON-OHE model, predicting the risk of future overt hepatic encephalopathy, was developed using multifactorial frailty competing risk analysis and rapid unified random forest models. External validation of the AMMON-OHE model was performed using two independent liver cohorts (267 and 381 patients, respectively).
The results showed that based on PHES and CFF tests and blood ammonia measurements, there were significant differences in the time to the occurrence of OHE in patients with different states (log-rank P<0.001). Patients with abnormal PHES and elevated blood ammonia (above normal upper limit) had the highest probability of developing overt hepatic encephalopathy (HR: 4.4; 95% CI: 2.4-8.1, compared to normal PHES and AMM-ULN, P<0.001) (Figure 1). Multivariate analysis results showed that high blood ammonia was an independent risk factor for the development of overt hepatic encephalopathy (HR: 1.4; 95% CI: 1.1-1.9; P=0.015), while PHES and CFF were not. The AMMON-OHE model (including gender, diabetes, albumin, creatinine, and AMM-ULN) outperformed PHES and CFF in predicting the first occurrence of overt hepatic encephalopathy in outpatient cirrhosis patients, with C-indices of 0.844 and 0.728 in the two validation cohorts, respectively.
Figure 1: Correlation Analysis of Parameters with OHE Occurrence and Survival
Therefore, the researchers concluded that this study developed and validated the AMMON-OHE model for identifying the risk of the first occurrence of overt hepatic encephalopathy in outpatient cirrhosis patients.
Expert Commentary
The role of blood ammonia, neuropsychological, and psychophysical tests in the diagnosis of MHE is crucial, but further research is needed to determine whether abnormalities in these indicators are correlated with the progression of overt hepatic encephalopathy.
This study evaluated the risk of the first occurrence of overt hepatic encephalopathy in cirrhosis patients based on blood ammonia measurements, neuropsychological, and psychophysical tests, in combination with common clinical and biochemical indicators. The researchers found that patients with abnormal PHES were more likely to develop OHE, but compared to abnormal PHES and CFF, blood ammonia levels could independently serve as a risk factor for OHE occurrence. Adding high AMM-ULN to the PHES test significantly improved its ability to stratify OHE and predict the risk of death.
Furthermore, the researchers developed a new app based on the AMMON-OHE model, which can help clinicians assess the likelihood of overt hepatic encephalopathy and the occurrence of related adverse events in outpatient cirrhosis patients. This provides a theoretical basis for further clinical intervention and is of significant clinical importance.
Reference
[1] Ballester MP, Tranah T, Balcar L, et al. Development and validation of the AMMON-OHE model to risk stratify cirrhosis outpatients for occurrence of overt hepatic encephalopathy. Journal of Hepatology 2023 vol. 78(S1) | S1–S99. EASL 2023. Abstract OS-035-YI.
Yangjie Li, Doctoral Student, Department of Gastroenterology, Capital Medical University.
Reviewed by Dr. Huiguo Ding, Director of the Hepatology and Digestive Center, Capital Medical University Affiliated Beijing You’an Hospital, Professor, and Doctoral Supervisor.
