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Diagnosis of minimal hepatic encephalopathy (MHE) requires psychometric testing, which is time-consuming and often neglected in clinical practice. Elevated Interleukin-6 (IL-6) serum levels have been linked to MHE. The aim of this study was to investigate the usefulness of IL-6 as a biomarker in a stepwise diagnostic algorithm to detect MHE in patients with liver cirrhosis. A total of 197 prospectively recruited patients without clinical signs of hepatic encephalopathy (HE) served as the development cohort. Another independent cohort consisting of 52 patients served for validation purposes. Psychometric Hepatic Encephalopathy Score (PHES) was applied for the diagnosis of MHE. Fifty (25.4%) patients of the development cohort presented with MHE. Median IL-6 levels were more than twice as high in patients with MHE than in patients without HE (16 vs. 7 pg/mL; P < 0.001). On multivariable logistic regression analysis, higher IL-6 levels (odds ratio 1.036; 95% confidence interval [CI] 1.009-1.064; P = 0.008) remained independently associated with the presence of MHE. IL-6 levels ≥ 8pg/mL discriminated best between patients with and without MHE in receiver operating characteristic (ROC) analysis (area under the ROC 0.751). With a cutoff value of ≥7 pg/mL, further elaborate testing with PHES could be avoided in 38% of all patients with a sensitivity of 90% (95% CI 77%-96%) and a negative predictive value (NPV) of 93% (95% CI 84%-98%). This diagnostic accuracy was confirmed in the validation cohort (sensitivity 94%; NPV 93%). Conclusion: Using IL-6 serum levels as a biomarker in a stepwise diagnostic algorithm to detect MHE could substantially reduce the number of patients requiring testing with PHES and in turn the workload. IL-6 may have especially helped in patients who are unable to perform other screening tests., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: In contrast to overt hepatic encephalopathy (OHE), the diagnosis of minimal HE (MHE) is challenging in patients with cirrhosis requiring elaborate, specialized testing. The EncephalApp&#95;Stroop is a smartphone-based application established as screening tool for the diagnosis of MHE but has not yet been validated in a German cohort and country specific cut-offs are currently missing., Methods: 93 patients with cirrhosis were enroled into this study. Psychometric hepatic encephalopathy score (PHES) was used to detect MHE, and a subset of the patients was tested with critical flicker frequency (CFF). All patients underwent testing with EncephalApp&#95;Stroop. Cut-off thresholds for EncephalApp&#95;Stroop were calculated according to Youden's Index and a separate cut-off was determined with focus on sensitivity., Results: 24 (26%) patients had MHE according to PHES. EncephalApp&#95;Stroop had a strong correlation with PHES (r=-0.76, p<0.001), while there was only a modest correlation with CFF (r=-0.51, <0.001). On time as well as on+off time discriminated best between patients with and without MHE with AUROCS of 0.87 for both measures. According to Youden's index, a cut-off of >224.7 s (sec) (on+off time) discriminated best between patients with and without MHE with a sensitivity of 71% and a specificity of 88%. The adjusted cut-off value for on+off time with focus on sensitivity (sensitivity:specificity weighed 2:1) was 185.1 s, yielding an optimized sensitivity of 92% and a negative predictive value of 96%. By using this cut-off as a pre-screening test in a stepwise diagnosis algorithm, elaborate testing with PHES could have been avoided in 49% of all patients., Conclusion: EncephalApp&#95;Stroop may be useful in a stepwise diagnosis algorithm or even as a stand-alone screening tool to detect MHE in German patients with cirrhosis., Competing Interests: Declaration of Competing Interest The authors disclose no potential financial or non-financial conflicts of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Non-selective β-blockers (NSBB) are frequently used for the treatment of portal hypertension and gastroesophageal varices in patients with liver cirrhosis; however prospective studies investigating the potential association between NSBB use and hepatic encephalopathy (HE) are still scarce. We investigated the potential association between NSBB use and the presence of covert HE (CHE) as well as the development of overt HE (OHE)., Methods: 224 patients with liver cirrhosis were included into this cohort study at two German centers and followed for a median of 364 days. CHE was diagnosed by pathological results in the PHES. Predictors for the presence of CHE or the development of OHE were analyzed using logistic-regression or cox-regression models., Results: 39% of patients were treated with NSBB and CHE was detected in 34% of patients at study inclusion. In logistic regression analysis, NSBB use, higher MELD score and a history of OHE were independently associated with the presence of CHE. Cumulative incidence of OHE was considerably higher in NSBB users than in non-users (p<0.001). In Cox-regression models NSBB use, presence of CHE, lower albumin and higher MELD score were independently associated with the development of OHE in the whole cohort as well as in the subgroup of patients with decompensated liver cirrhosis. NSBB use was independently associated with higher risk of mortality or need for liver transplantation in decompensated patients but not in the total cohort., Conclusion: NSBB use seems to be associated with the presence of CHE as well as the development of OHE in patients with decompensated liver cirrhosis., (Copyright © 2020. Published by Elsevier B.V.)

Background: Diabetes mellitus may lead to increased serum ammonia and systemic inflammation thereby promoting hepatic encephalopathy (HE)., Aim: To investigate the potential association between diabetes mellitus/glycaemic control and the presence of covert HE as well as the development of overt HE in a prospective setting., Methods: A total of 240 patients with liver cirrhosis were included into this prospective cohort study and followed for a median of 17 months. Covert HE was diagnosed by pathological results in the Portosystemic Hepatic Encephalopathy Score. Predictors for the presence of covert HE or the development of overt HE were analysed using logistic regression or Cox-regression models., Results: At study inclusion, 65 patients (27.1%) presented with diabetes mellitus and covert HE was detected in 33.3%. Patients with diabetes mellitus had a more preserved liver function as compared to patients without diabetes mellitus (MELD 9 vs 10; P = 0.043). In regression analyses after adjustment for confounders, diabetes mellitus was independently associated with the presence of covert HE at study inclusion and the development of overt HE during follow-up. These associations were confirmed in separate propensity-score-weighted regression models. In subgroup analyses, patients with worse glycaemic control (HbA1c >= 6.5%) had a pronounced risk for covert HE (OR 2.264, 95% CI 1.002-5.118) and overt HE (HR 4.116, 95% CI 1.791-9.459)., Conclusions: Diabetes mellitus may associate with higher risk for the presence of covert HE and the development of overt HE in patients with liver cirrhosis. Adequate glycaemic control may be a potential target to attenuate this important complication., (© 2020 John Wiley & Sons Ltd.)