In this multicenter study, EncephalApp, using adjusted population norms or in the context of existing gold standard tests, had good sensitivity for MHE diagnosis and predictive capability for OHE development.

Background Hypovitaminosis D is common in obesity and insulin resistant states. Increased fat mass in patients with non-alcoholic fatty liver disease (NAFLD) may contribute to hypovitaminosis D. Aims To determine the relation between plasma vitamin D concentration, severity of disease and body composition in NAFLD. Methods Plasma vitamin D concentration was quantified in 148 consecutive biopsy proven patients with NAFLD (non alcoholic steatohepatitis-NASH: n=81; and hepatic steatosis n=67) and healthy controls (n=39). NAFLD was scored using the NASH CRN criteria. Body composition was quantified by bioelectrical impedance analysis and abdominal CT image analysis. Results Plasma vitamin D concentration was significantly lower in NAFLD (21.2±10.4 ng/ml) compared to healthy controls (35.7±6.0 ng/ml). Higher NAFLD activity scores were associated with lower plasma concentration of vitamin D (r2=0.29; p<0.001). Subgroup analysis among patients with NAFLD showed that patients with NASH had significantly lower (p<0.01) vitamin D levels than those with steatosis alone (18.1±8.4 vs. 25.0±11.3 ng/ml). Low concentrations of vitamin D were associated with greater severity of steatosis, hepatocyte ballooning and fibrosis (p<0.05). On multivariate regression analysis, only severity of hepatocyte ballooning was independently associated (p=0.02) with low vitamin D concentrations. Plasma vitamin D (p=0.004) and insulin concentrations (p=0.03) were independent predictors of the NAFLD activity score on biopsy. Patients with NAFLD had higher fat mass that correlated with low vitamin D (r2=0.26; p=0.008). Conclusions Low plasma vitamin D concentration is an independent predictor of the severity of NAFLD. Further prospective studies demonstrating the impact of vitamin D replacement in NAFLD patients are required.

Background & Aims: Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Methods: Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. Results: We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT+StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k=0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33-45% range. CHE diagnosis by PHES

Background & Aims In patients with cirrhosis, cognitive dysfunction most often results from covert hepatic encephalopathy (HE). These patients are not routinely tested for cognitive dysfunction, despite single-center evidence that it could be associated with poor socio-economic status (SES). We investigated the association between SES and cognition in a multi-center study of cirrhosis. Methods In a cross-sectional study, 236 cirrhotic patients from 3 centers (84 subjects from Virginia, 102 from Ohio, and 50 from Rome, Italy; age 57.7±8.6 y; 14% with prior overt HE) were given recommended cognitive tests and a validated SES questionnaire, which included questions about employment, personal and family income, and overall financial security. Comparisons were made among centers and between subjects who were employed or not. Regression analysis was performed using employment and personal income as outcomes. Results Only 37% of subjects had been employed in the last year. Subjects had substantial financial insecurity—their yearly personal income ranged from $16,000 to $24,999 and their family income ranged from $25,000 to $49,999. They were only able to maintain a residence for 3–6 months if their income stopped, and their current liquid assets were $500–$4999 (<$500 if debt was subtracted). Cognition and SES were worst in Ohio and best in Virginia. Cognition correlated with personal and family income, within and between centers. On regression analysis, cognitive performance (digit symbol, lures, and line tracing) was associated with personal yearly income, after controlling for demographics, country, employment, and overt HE. Unemployed subjects had a higher rate of overt HE, worse cognition, and lower personal income than employed subjects. On regression analysis, performance on digit symbol, line tracing, inhibitory control test lures, and serial dotting tests remained associated with income, similar to employment. Conclusions In an international, multi-center study of patients with cirrhosis, socio-economic condition, based on employment and personal income, was strongly associated with cognitive performance, independent of age, education, and country.

In this multicenter study, prior HE patients showed persistent significant learning impairment compared to those without prior HE, despite adequate medical therapy. This persistent change should increase efforts to reduce the first HE episode.

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Ever since the advent of liver transplantation, there has been great interest in how effectively this procedure reverses hepatic encephalopathy (HE). Most clinicians believe that the majority of the clinical features recognized as HE are reversed by successful liver transplantation. 1 However, in this issue of Liver Transplantation, there is a report showing an incomplete reversal of certain cognitive defects in patients who had bouts of overt HE before they underwent liver transplantation. 2 Interestingly, abnormal electroencephalographic patterns that were noted in all these patients completely normalized after transplantation, whereas previously abnormal domains of cognition improved over a 12-month period but still were not normal in patients with a pretransplant history of overt HE.There have been a number of studies suggesting that once patients have had a bout of overt HE, they may be at risk for a less-than-full recovery of brain function even after liver transplantation. 3-5 Perhaps we might accept this lack of recovery in patients who have not received a new liver if they still appear to be normal on the surface. After all, HE therapy in patients with cirrhosis does appear to control overt HE, but a substantial number of patients treated with lactulose or rifaximin may still have minimal HE. Traditionally, in many contemporary studies of minimal HE, patients with previous overt HE have been excluded. It would be interesting to see whether the responses to HE therapy for minimal HE in patients with previous bouts of overt HE and patients without that history are different. Be that as it may, on the basis of the findings of the current study, we can conclude a few points. First, even though 23 of the patients (the total sample was 65) had histories of overt HE, it appears that none had overt HE around the time of transplantation. We assume that the patients were placed on therapy as is usual after bouts of overt HE. The domains of attention and executive function were more impaired in those patients who had previous bouts of overt HE even though they were treated for HE (we assume), and importantly, after liver transplantation, the performance on these domains remained lower than the performance of patients who had not experienced overt HE previously. In contrast, memory, which was also impaired before liver transplantation in patients who previously had overt HE, returned to a virtually normal state. Trail Making Test B seemed to be particularly sensitive for picking up the less reversible aspects of the domain of attention. This is well illustrated in Fig. 3 of the article. It must be admitted that the number of patients at the end of the study may have been insufficient to completely prove the lack of recovery in these patients.As mentioned earlier, if we accept that patients with a previous bout of overt HE may be unable to recover from a defect in the cognitive domain of attention or executive function even with a liver transplant, a more serious issue is raised. Should all patients undergo transpla...

Background/Aim: Most endoscopies performed in the United States utilize sedation. Anesthesia provides patient comfort and improved procedural quality but adds to the complexity of scheduling routine outpatient procedures. We aimed to assess the return of cognitive function after propofol administration in patients undergoing outpatient endoscopies. Patients and Methods: Cognitive recovery for patients undergoing endoscopy under monitored anesthesia care was evaluated using EncephalApp. Patients were tested before and after procedure and healthy controls were tested twice, 30 min apart. Results were tabulated in on state (on time) and off state (off time) and total time (on time + off time). The time difference between pre- and post-tests, “delta,” was calculated for on, off, and total times. Wilcoxon rank test was used to check the difference in mean delta of all three test times between cases and controls and to check for statistical significance. Results: The difference in mean time between cases and controls was significant for off ( P < 0.0001) and total ( P = 0.0002) times. No statistically significant difference was noted in mean time for on time ( P = 0.013) between cases and controls. Cognitive flexibility, a measure of on time, returned to baseline after procedural sedation even though psychomotor speed, a measure of off time and total time, had not. Conclusion: Cognitive flexibility returns to baseline within 30–45 min after propofol sedation despite delayed return of psychomotor speed and reaction time.