A Proof‐of‐Concept Study of Language‐Stratified Assessment for Minimal Hepatic Encephalopathy: Integrating the Animal Naming Test and Serum IL‐6

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ABSTRACT 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 (ANT 1 ) 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 ANT 1 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 ANT 1 , simplified ANT 1 (S‐ANT 1 ), 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‐ANT 1 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), ANT 1 demonstrated an AUROC of 0.760, while serum IL‐6 showed an AUROC of 0.841. The composite model combining ANT 1 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 ANT 1 showed a lower AUROC of 0.679. The exploratory Taiwanese‐calibrated S‐ANT 1 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 ANT 1 performance in MHE assessments. Integrating ANT 1 with serum IL‐6 showed numerically improved discrimination in Mandarin speakers, whereas exploratory demographic calibration of S‐ANT 1 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.

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