Value of Six Minimal Hepatic Encephalopathy Tests in Predicting Clinical Outcome in Patients With Liver Cirrhosis

Introduction: The development of overt hepatic encephalopathy (oHE) is a dreaded complication in patients with liver cirrhosis. Additionally, advanced liver disease is associated with increased risk of rehospitalization and mortality. The evaluation and comparison of prognostic values of different minimal hepatic encephalopathy (mHE) tests regarding these outcomes is an unmet need. We evaluated 6 widely used mHE tests regarding their predictive value for oHE, rehospitalization and death. Patients and Methods: In this prospective study, we recruited 132 patients with liver cirrhosis between August 2021 and April 2022. All patients performed a mHE assessment consisting of PSE-Syndrome Test (PHES), Animal Naming Test (ANT), Critical Flicker Frequency (CFF), Inhibitory Control Test (ICT), EncephalApp (Stroop) and Continuous Reaction Time Test (CRT). Patients were monitored for 365 days regarding development of oHE, rehospitalization and death. We performed competing risk analyses (treating death/liver transplantation as competitor) for oHE and rehospitalization and cox regression for death. Results: At baseline, median age was 57, median MELD 12 and Child Pugh Score 7. The majority of patients were male (69%) and had an alcohol-related liver cirrhosis (52%). 30% of patients had a history of oHE and approximately half of patients had evidence of mHE. During follow up, 24 (18%) patients developed oHE, 58 (44%) were re-admitted to hospital and 32 (24%) patients died. Pathological PHES was significantly linked to oHE development in competing risk analysis during follow up, ANT only with cut-off uncorrected for age and education (Figure 1). Regarding rehospitalization, only pathological PHES results showed a significant correlation in the competing risk analysis (HR: 1.801; P=0.031). Pathological uncorrected ANT results (<23 animals) but not normalized ANT Z-scores were significantly associated with mortality in cox regression (HR: 2.397; P=0.032). Pathological results in CRT, ICT, Stroop and CFF were not significantly linked to any endpoint (oHE, rehospitalization, death). Of note, all test parameters had inferior prognostic value than the standard laboratory test results assessed in liver patients. Conclusion: This study underlines the frequency of poor outcome in patients with cirrhosis and mHE. PHES was the most reliable prognostic value among the mHE tests in predicting oHE and rehospitalization.Figure 1.: Competing risk analyses for the prediction of oHE.