An Association of Covert Hepatic Encephalopathy with Non-elderly and MASLD in Patients with Chronic Liver Disease: Data-mining Analyses.

Background and Aims Covert hepatic encephalopathy (CHE) worsens the quality of life and the prognosis of patients with chronic liver disease (CLD). CHE can be caused by various factors, including age and the etiology of CLD, such as metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate factors associated with CHE in patients with CLD. Methods This retrospective study included 195 patients with CLD. CHE was diagnosed using Stroop test. Hyperammonemia was defined as a plasma ammonia level ≥80 μg/dL. The factors associated with CHE were evaluated using logistic regression, decision trees, and random forest analyses. Results The prevalence of CHE was 36.4%. According to a multivariate analysis, age (<65 years), hepatocellular carcinoma (HCC), and MASLD were identified as independent factors for CHE, whereas hyperammonemia was not (age: OR 4.36, p<0.0001; HCC: OR 4.07, p=0.0070; MASLD: OR 1.94, p=0.0500). A decision tree analysis identified age as the initial classifier; CHE prevalence was 62.5% in patients aged <65 years and 25.9% in those aged ≥65 years. Among the patients aged <65 years, MASLD was the next most significant classifier with a CHE prevalence of 90.5%. A random forest analysis confirmed that age was the highest-ranking factor associated with CHE, followed by MASLD score. Conclusion Age <65 years is the most important factor associated with CHE. Among these patients, MASLD was the second most significant factor. Accordingly, non-elderly age and MASLD may be the main pathogenic drivers of CHE in this era of steatotic liver disease.