Association Between Laboratory Values and Covert Hepatic Encephalopathy in Patients with Liver Cirrhosis: A Multicenter, Retrospective Study

Background/Objective: Recently, there has been an increasing need to implement the diagnosis of the presence of covert hepatic encephalopathy (CHE) in patients with cirrhosis. The aim of this study was to identify novel factors associated with CHE in clinical practice. Methods: This retrospective study enrolled a total of 402 patients with cirrhosis at 17 institutions. The Stroop test was performed to diagnose CHE at each center. Results: The patients comprised 233 males and 169 females, with a median age of 69 (IQR, 61–75) years. The median albumin and 25(OH)D3 levels were 3.9 (3.5–4.3) g/dL and 15.4 (11.0–21.0) ng/mL, respectively. This cohort included 181 patients with esophageal varices (EV). Multivariate analysis revealed that low 25(OH)D3 (p < 0.05) and EV (p < 0.05) were independent risk factors for CHE. When limited to only laboratory factors, low albumin (p < 0.01) and low 25(OH)D3 (p < 0.05) were independent factors for CHE. The optimal cut-off values of albumin and 25(OH)D3 for predicting CHE were 3.7 g/dL and 16.5 ng/mL, respectively. The prevalence of CHE was 59.2% for 25(OH)D3 < 16.5 ng/mL and EV, 53.8% for albumin < 3.7 g/dL and 25(OH)D3 < 16.5 ng/mL, and 66.7% for albumin < 3.7 g/dL, EV, and 25(OH)D3 < 16.5 ng/mL. Conclusions: Low 25(OH)D3 and albumin levels, and the EV were positively associated with CHE in patients with cirrhosis. Specifically, the prevalence of CHE increased with a decrease in 25(OH)D3 levels. Patients with such risk factors should be actively and carefully examined for the presence of CHE.