A Proof-of-Concept Study of Language-Stratified Assessment for Minimal Hepatic Encephalopathy: Integrating the Animal...

Minimal hepatic encephalopathy (MHE) involves subtle cognitive dysfunction and systemic inflammation and is associated with an increased risk of overt hepatic encephalopathy. The Animal Naming Test (ANT₁) is a rapid semantic fluency tool for MHE assessment, but its performance across different primary spoken languages remains unclear. We conducted a prospective proof-of-concept study to evaluate the diagnostic performance of ANT₁ and serum interleukin-6 (IL-6) in Mandarin- and Taiwanese Hokkien-speaking cirrhotic patients. A total of 65 cirrhotic patients and 34 healthy controls were enrolled. Patients completed ANT₁, simplified ANT₁ (S-ANT₁), and standard psychometric assessments. MHE was defined by abnormal PHES and/or visually assessed EEG slowing. Diagnostic discrimination was evaluated using AUROC analyses stratified by primary spoken language. A post hoc exploratory Taiwanese-calibrated S-ANT₁ was also assessed in Taiwanese Hokkien-speaking patients. Sixteen cirrhotic patients (24.6%) were diagnosed with MHE. Patients with MHE had lower ANT1 scores and higher serum IL-6 levels than those without MHE. In Mandarin-speaking patients (n = 44), ANT₁ demonstrated an AUROC of 0.760, while serum IL-6 showed an AUROC of 0.841. The composite model combining ANT₁ and serum IL-6 showed a numerically higher AUROC of 0.895, but this improvement was not statistically significant in pairwise DeLong comparisons. In Taiwanese Hokkien-speaking patients (n = 21), standard ANT₁ showed a lower AUROC of 0.679. The exploratory Taiwanese-calibrated S-ANT₁ showed a numerically higher AUROC of 0.776; however, this post hoc finding was based on a small subgroup with 7 MHE events and requires external validation. This study suggests that primary spoken language may be associated with ANT₁ performance in MHE assessments. Integrating ANT₁ with serum IL-6 showed numerically improved discrimination in Mandarin speakers, whereas exploratory demographic calibration of S-ANT₁ showed a numerically higher AUROC in Taiwanese Hokkien speakers. These findings are exploratory and hypothesis-generating, necessitating validation in larger independent cohorts before clinical implementation.