Prediction and prevention of the first episode of overt hepatic encephalopathy in patients with cirrhosis

Abstract

Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients’ quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.

PHES scores have limited impact on the risk of overt HE in patients with minimal HE

“…Identification of high-risk patients for OHE development is important for the management of patients with cirrhosis 4 and MHE is a well-known risk factor for OHE; however, our study demonstrates that within the group of patients with MHE, worse results in PHES cannot be taken to reflect a higher OHE risk. This may relate to the fact that cognitive function varies from patient to patient, and PHES results are not only affected by MHE.…”

“… 3 Therefore, identifying high-risk patients in the subgroup of patients with MHE could be beneficial to establishing strategies to prevent OHE in routine clinical practice and for purposes of future interventional trials. 4 This study aimed to investigate whether there is a stepwise increase in OHE risk with worse PHES results in patients with PHES-MHE.…”

Use of bee venom in preventive medicine: An experimental hepatic encephalopathy study in rats

“…In hepatic encephalopathy, ammonia removal has been identified as the main mechanism for prevention and prophylaxis (Butterworth, 2021 ). A recent review aimed at preventing and predicting hepatic encephalopathy revealed two recommendations, energy and protein intake, and pharmacological prevention, which only included two studies, one on lactulose study, the other on probiotics, and the authors stated that no other studies were found as primary prevention goals (Gairing et al., 2023 ).…”

EncephalApp Stroop Test as a Screening Tool for the Detection of Minimal Hepatic Encephalopathy in Patients with Cirrhosis—Single-Center Experience

“…OFF time (total time for five correct runs in the "OFF" state), 2. ON time (total time for five correct runs in the "ON" state), 3. time difference (ON time minus OFF time), and 4. total time (ON time plus OFF time) [11,14,15].…”

“…From the several studies performed by Bajaj et al, as well as from the results of studies from other countries, it can be concluded that various socio-demographic factors, such as the level of education and smartphone use experience, can significantly influence the test results [14]. Even though official recommendations cannot be made regarding the primary prophylaxis of OHE, given its importance and significance, the EncephalApp Stroop test has been increasingly (although externally) used not only for MHE identification but also for the prediction of the first OHE episode as well [15]. Therefore, there is a justified need to validate this test for different populations.…”