Development and clinical evaluation of the modified Hepatic Encephalopathy Staging Tool.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a serious complication of advanced cirrhosis, requiring accurate and consistent diagnosis and staging. The commonly used West Haven criteria have substantial inter-observer variability. This study aimed to develop the modified Hepatic Encephalopathy Staging Tool (mHEST) as a more objective and reproducible HE-assessment method for regulated clinical trials. METHODS: This study consisted of two parts. In Part 1, 49 healthcare professionals from six countries evaluated six video vignettes depicting different HE-stages. After viewing a mHEST training video, participants assessed the vignettes twice (5-10 days apart). Inter- and intra-rater agreement were analyzed. In Part 2, a prospective single-center study enrolled 128 hospitalized patients with decompensated cirrhosis. Trained professionals independently assessed HE using both West Haven and mHEST. Diagnostic consistency, prognostic performance, and impact on established scoring systems were compared. RESULTS: In Part 1, inter-rater concordance ranged from 83.3% to 100%, and intra-rater agreement from 81.0% to 100%. In Part 2, inter-rater reliability was significantly higher for mHEST than West Haven (κ= 0.934 vs. 0.367). mHEST improved the performance of HE-containing scores, including Child-Pugh and CLIF-C Organ Failure. Plasma ammonia levels increased stepwise with mHEST grades, but not with West Haven. mHEST grades correlated with one-year mortality, and low mHEST grades (0-1) independently predicted improved one-year survival. CONCLUSION: MHEST is a user-friendly, reliable, and prognostically accurate HE-assessment tool that outperforms West Haven and has been accepted by the U.S. Food and Drug Administration as a clinical trial endpoint.