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Selenium is an essential trace element to maintain good health. This retrospective study investigated the prevalence of selenium deficiency and its effect on overt hepatic encephalopathy (OHE) in patients with chronic liver disease (CLD). Patients who underwent serum selenium level measurement between January 2021 and April 2022 were enrolled. The factors associated with selenium deficiency (≤10 µg/dL) and the association between selenium deficiency and OHE were analyzed. Among 98 eligible patients, 24% were observed to have selenium deficiency, with a median serum selenium level of 11.8 µg/dL. The serum selenium levels were significantly lower in patients with cirrhosis than in those with chronic hepatitis (10.9 µg/dL vs. 12.4 µg/dL; p = 0.03). The serum selenium levels were negatively correlated with mac-2 binding protein glycan isomer, the FIB-4 index, albumin-bilirubin (ALBI) score, and Child–Pugh score. The ALBI score remained significantly associated with selenium deficiency (odds ratio, 3.23; 95% confidence interval [CI], 1.56–6.67). During a median follow-up period of 2.9 months, nine patients experienced OHE. Selenium deficiency was associated with OHE (hazard ratio, 12.75; 95% CI, 2.54–70.22). Selenium deficiency is highly prevalent in patients with CLD and is associated with an increased risk of OHE development. [ABSTRACT FROM AUTHOR]

Circulating albumin structures, including their oxidized and reduced forms, are involved in hepatic encephalopathy (HE) development. However, the effects of rifaximin, a key drug in HE treatment, on the circulating albumin structure in patients with liver cirrhosis remain unclear. In this multicenter prospective study, eight patients with hyperammonemia (≥80 μg/dL) were enrolled. The circulating albumin structure was evaluated using the ratio of oxidized albumin (human nonmercaptalbumin, HNA). Patients were administered 400 mg rifaximin 3 times/day for 3 months, and laboratory data were assessed at baseline and during observation. Among the eight patients, three were men; the median age and body mass index were 70 years and 26.4 kg/m2, respectively. The median HNA and serum ammonia levels at baseline were 41% and 143 μg/dL, respectively. After rifaximin therapy, HNA showed a decreasing tendency (median; from 41% to 36%, p = 0.321), but serum albumin levels showed no significant change (from 3.5 g/dL to 3.5 g/dL, p = 1.00); serum ammonia levels significantly reduced (median: 143 μg/dL to 76 μg/dL, p = 0.015). Thus, rifaximin reduces serum ammonia levels and may improve circulating albumin structure in patients with cirrhosis. Further large-scale studies are required to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Background: Covert hepatic encephalopathy (CHE) adversely affects the clinical outcomes of patients with cirrhosis but remains largely undiagnosed and untreated. Although the Stroop test is a useful method for CHE detection, a faster, simpler, and more accurate test is required to diagnose CHE. This prospective study aimed to develop a new shortened Stroop test that can detect CHE and predict overt hepatic encephalopathy (OHE) in Japanese patients with cirrhosis. Methods: Patients who underwent neuropsychological tests (NPT) and the Stroop test between November 2018 and December 2021 were enrolled and followed until OHE occurrence or March 2022. The discriminative ability of various run combinations in the off and on states to detect CHE was evaluated using the area under the receiver-operating characteristic curve (AUC) and compared with that of the total Stroop test time. Results: Among the 227 eligible patients, the On1–2Time cutoff value of 44.4 s had a comparable discriminative ability with the total Stroop test time to detect CHE, with an AUC of 0.791, a sensitivity of 0.827, and a specificity of 0.685. During a median follow-up period of 16 months, 37 patients developed OHE. On1–2Time ≥ 44.4 s (hazard ratio [HR], 3.93; 95% confidence interval [CI] 1.36–11.36) and serum albumin levels (HR, 0.28; 95% CI 0.11–0.67) were independently associated with OHE occurrence. Conclusions: The shortened Stroop test (On1–2Time) is equivalent to the total Stroop test not only for identifying CHE but also for estimating the risk of progression to OHE. [ABSTRACT FROM AUTHOR]

Aim: Covert hepatic encephalopathy (CHE) adversely affects clinical outcomes in patients with liver cirrhosis, although its diagnosis is difficult. This study aimed to establish a simple CHE screening model based on blood-related biochemical parameters. Methods: This retrospective study enrolled 439 patients who were assessed for CHE using a neuropsychiatric test between January 2011 and June 2019. A simple CHE (sCHE) score was calculated with hypoalbuminemia (≤ 3.5 g/dL) and hyperammonemia (≥ 80 μg/dL) as 1 point each. The association between sCHE score and CHE or overt hepatic encephalopathy (OHE) was assessed using logistic regression and Fine-Gray competing risk regression models. Results: Of 381 eligible patients, 79 (21%) were diagnosed with CHE. The distribution of sCHE scores was 48% with 0 point, 33% with 1 point, and 19% with 2 points. Patients with sCHE score ≥ 1 point had a higher prevalence of CHE than those with sCHE score of 0 (27% vs. 14%, P = 0.002). A cut-off value of 1 point showed high discriminative ability for identifying CHE, with a sensitivity of 0.67, specificity of 0.56, positive predictive value of 0.27, and negative predictive value of 0.86. During the median follow-up period of 2.2 years, 58 (15%) patients developed OHE. Multivariate analysis showed that sCHE score ≥ 1 (sub-distribution hazard ratio [SHR], 2.69; 95% confidence interval [CI], 1.41–5.15) and CHE (SHR, 2.17; 95% CI, 1.26–3.73) independently predicted OHE. Conclusions: The sCHE score is a useful screening model for identifying patients with CHE and for predicting OHE occurrence. [ABSTRACT FROM AUTHOR]

Aim: Minimal hepatic encephalopathy (MHE) is associated with poor outcomes and the development of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis (LC). Zinc plays a key role in the detoxification of ammonia, a risk factor of hepatic encephalopathy. This study aimed to investigate whether zinc deficiency predicts OHE occurrence and mortality in LC patients with MHE. Method: This retrospective study included 100 LC patients with MHE. MHE was diagnosed using a computer‐aided neuropsychiatric test. Predictors associated with the development of OHE were analyzed using the Fine–Gray competing risk regression model. Cox proportional hazards regression analysis was carried out to evaluate the risk factors of mortality. Survival rates were analyzed using the Kaplan–Meier method and log‐rank test. Results: Of the 100 LC patients with MHE, 41% had zinc deficiency (<60 μg/dl). Zinc deficiency was observed more frequently in the patients with reduced liver function reserve. During the median follow‐up period of 9.9 months, 16% of the patients with MHE developed OHE. The patients with zinc deficiency had a higher risk of OHE than those without zinc deficiency (p = 0.03). Zinc deficiency was also associated with poor survival (p = 0.004). Multivariate analyses showed that zinc predicts the development of OHE (subdistribution hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.92–0.99; p = 0.008) and mortality (HR, 0.96; 95% CI, 0.93–0.99; p = 0.02), independently of liver function reserves. Conclusion: Zinc deficiency is likely to be a predictor of both OHE development and mortality in LC patients with MHE. [ABSTRACT FROM AUTHOR]

Background and Aim: Minimal hepatic encephalopathy (MHE) represents the mildest form of the hepatic encephalopathy spectrum. This study aimed to clarify the prognostic significance of MHE in cirrhotic patients. Methods: This retrospective study evaluated 357 consecutive patients with liver cirrhosis. MHE was diagnosed using a neuropsychiatric test. A propensity score‐matching analysis was employed to adjust significant differences in the baseline characteristics between patients with and without MHE. Results: Of 269 eligible patients, 56 patients (21%) were diagnosed as having MHE. The Child–Pugh score, model for end‐stage liver disease score, and serum ammonia levels were significantly increased, while serum albumin levels were reduced in patients with MHE. By contrast, no significant difference was found between the two groups in matched patients. During the median follow‐up period of 13.4 months, 67 patients (24.9%) died. Overall survival rates were significantly lower in patients with MHE (median, 25.4 vs 48.8 months; P < 0.001). Multivariate analysis revealed that male sex (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.03–3.18; P = 0.038), stage III/IV hepatocellular carcinoma (HR, 6.32; 95% CI, 3.30–12.79; P < 0.001), the Child–Pugh score (HR, 1.35; 95% CI, 1.12–1.62; P = 0.002), and MHE (HR, 1.92; 95% CI, 1.09–3.29; P = 0.024) were independently associated with mortality in all patients as well as in matched patients. Conclusion: Minimal hepatic encephalopathy is associated with an increased risk of mortality in patients with liver cirrhosis, independent of hepatocellular carcinoma stage or Child–Pugh score. [ABSTRACT FROM AUTHOR]

Aim: The inability to quickly react to an external event can lead to an increased risk for accidents (e.g., falls, car crashes) in patients with cirrhosis. The aim of this study was to determine whether a novel clinically feasible measure of simple reaction time (SRT) and reaction accuracy (RA)—a go/no‐go task occurring within 400 ms—could differentiate patients with cirrhosis from controls. Methods: This retrospective study included 160 patients with cirrhosis and 160 controls assessed between January 2010 and October 2022. SRT and RA were evaluated using a ruler drop paradigm and compared using propensity score matching. Factors distinguishing patients with cirrhosis from controls were assessed using logistic regression and receiver operating characteristics curve (ROC) analyses. Results: Propensity score matching identified 112 participants in each group with comparable baseline characteristics. As compared with controls, patients with cirrhosis exhibited significantly prolonged SRT (200 vs. 174 ms; P < 0.001) and diminished total RA (63% vs. 73%; P < 0.001). After adjustment for confounding factors, SRT and RA independently identified patients with cirrhosis. ROC analyses showed that SRT more effectively identified patients with cirrhosis than did the number‐connection test/trail‐making test‐B (area under the curve, 0.87 vs. 0.60; P < 0.001). Conclusions: Patients with cirrhosis demonstrated impairments in short‐latency cognitive function. Given that SRT and RA are associated with balance, falls, and response to perturbation, these parameters may present a task‐specific method to identify patients with cirrhosis at high risk of falls and motor vehicle crashes. Geriatr Gerontol Int 2024; 24: 25–31. [ABSTRACT FROM AUTHOR]

Aim: Sleep disorder is common in patients with chronic liver disease (CLD). Liver‐related silent complications, including muscle cramps, covert hepatic encephalopathy (HE), and sarcopenia, often reduce the quality of life of patients with CLD and have been reported to cause sleep disorders. In this study, we clarified the prevalence of liver‐related complications associated with sleep disorders in patients with CLD. Methods: We conducted a multicenter cohort study of 271 patients with CLD. The Athens Insomnia Scale, muscle cramps questionnaires, and Stroop test were used to assess insomnia, muscle cramps, and covert HE, respectively. In addition, sarcopenia, dynapenia, and myopenia were diagnosed according to the guidelines of the Japan Society of Hepatology. Results: In total, 136 patients (50.2%) had sleep disorders. Serum albumin and hemoglobin levels and prothrombin time activity were significantly lower in patients with sleep disorders than in those without sleep disorders. On univariate and multivariate analyses adjusted with inverse probability weighting, muscle cramps, covert HE, and dynapenia were associated with a sleep disorder. Sleep disorder was categorized as follows: cramp, covert HE, dynapenia, multiple complications, and others. In total, 106 of 136 patients (77.9%) with sleep disorder had at least one liver‐related complication, whereas 75 patients had multiple liver‐related complications. Conclusion: Sleep disorder in patients with CLD was classified into four categories (muscle cramp, covert HE, dynapenia, and others). Questionnaire for sleep disorder might be an easy primary step for surveillance of high‐risk patients with silent complications associated CLD. [ABSTRACT FROM AUTHOR]

Aim: Despite its relevant clinical impact and high prevalence, covert hepatic encephalopathy (HE) still remains underdiagnosed. As patients with liver cirrhosis tend to be older in Japan, more suitable tests for the elderly and cut‐off values based on this attribute are needed. Recently, a Stroop test has been developed and validated for the screening and diagnosis of covert HE in the United States. The present study aims to establish the cut‐off values of the Stroop test to screen covert HE. Methods: This study was a prospective multicenter cross‐sectional endeavor. We undertook a survey of 311 cirrhotic patients, administering the number connection test (NCT)‐A and ‐B and the Stroop‐off and ‐on test. Results: We determined the cut‐off values of Stroop test results for cirrhotic patients in a variety of age ranges. The cut‐off value of the Stroop test was strongly correlated with age. There was a significant correlation between the results of NCT‐B and age, and Stroop‐on test results showed a correlation with serum albumin (Alb) levels. Serum Alb ≤3.2 g/dl could have the potential to be an objective biomarker of covert HE. In addition, stepwise logistic regression analysis revealed a relationship between the results of the Stroop‐on test and plasma ammonia levels. Conclusions: We established the cut‐off values of Stroop test results and confirmed the efficacy of the Stroop test as a simple tool for assessing cognitive alterations. The Stroop test could be suitable as a necessary minimum for the diagnosis of covert HE. [ABSTRACT FROM AUTHOR]