Outcome prediction of covert hepatic encephalopathy in liver cirrhosis: comparison of four testing strategies

Question:

Despite the negative impact of covert hepatic encephalopathy (CHE) on the outcome of patients with liver cirrhosis, data regarding the ability of different testing strategies to predict overt hepatic encephalopathy (OHE) development and mortality are limited. This study aimed to compare the ability of Psychometric Hepatic Encephalopathy Score (PHES), critical flicker frequency (CFF), simplified animal naming test (S-ANT1) and Clinical CHE (CCHE) score to predict OHE development and mortality.

Methods:

367 patients with liver cirrhosis were screened for this prospective study between March 2017 and December 2018 at the University Medical Center in Mainz and the Diakonie Klinikum Siegen. Patients were excluded if they fulfilled one of the following criteria: previous episode of OHE during the last three months, the presence of malignancies, chronic alcohol consumption or neurological comorbidities. All patients were tested with the different testing strategies and prospectively followed regarding clinically relevant outcomes (OHE or death/liver transplantation).

Results:

A total of 252 patients with liver cirrhosis were enrolled in Mainz and Siegen. Follow-up data were available for 224 patients with a median follow-up time of 364 days (IQR 202; 508). During follow-up, 39 patients (17.0%) developed an episode of OHE and 45 patients died or received a liver transplantation. The majority of the patients were male (56.7%) with a median MELD score of 10 (7; 14). Prevalence of pathological results varied among the testing strategies: PHES 33.9%, CFF 17.9%, S-ANT1 41.5%, and CCHE score 33.9%. All testing strategies were independent predictors of OHE development after adjusting for MELD score and history of OHE. The predictive performances of PHES (AUROC, 0.742) and CCHE (AUROC, 0.785) regarding OHE development during the next 180 days were significantly better than of CFF and S-ANT1. In multivariable analysis, pathological results in PHES, S-ANT1 and CCHE were independently associated with higher mortality. CFF did not correlate with mortality in the whole cohort. In the subgroup of patients with a MELD score < 15, pathological results in PHES, CFF or CCHE were independent predictors of higher mortality.

Conclusion:

PHES and CCHE score predict OHE development and mortality in patients with liver cirrhosis. In particular, in patients with low MELD score both testing strategies could help to identify patients who may benefit from liver transplantation.