Portosystemic Encephalopathy Syndrome Research Articles

The prevalence and risk factors for cognitive impairment in obesity and NAFLD.

Severe obesity may be accompanied by cognitive dysfunction and NAFLD, but the associations remain unclear. We describe the prevalence and features of cognitive dysfunction and examine the associations between cognitive dysfunction and the presence and severity of NAFLD, and the associations between cognitive dysfunction and signs of other obesity-related comorbidities and neuronal damage. A cross-sectional study of patients with a body mass index of 35kg/m2 underwent evaluation for bariatric surgery. They were screened for adiposity-related comorbidity and underwent a liver biopsy and basic cognitive testing with the Continuous Reaction Time test, the Portosystemic Encephalopathy Syndrome test, and the Stroop Test. A representative subgroup also underwent the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The primary study outcome was "cognitive impairment," defined as ≥2 abnormal basic cognitive tests and/or an abnormal RBANS. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) served as a biomarker for neuronal damage. We included 180 patients; 72% were women, age 46 ± 12 years, 78% had NAFLD, and 30% with NASH without cirrhosis. 8% were cognitively impaired by the basic tests and 41% by RBANS results. Most impaired were executive and short-time memory functions. There were no associations between cognitive impairment and BMI, NAFLD presence or severity, or metabolic comorbidities. Male sex (OR: 3.67, 95% CI, 1.32-10.27) and using 2 or more psychoactive medications (5.24, 95% CI, 1.34-20.4) were associated with impairment. TREM2 was not associated with cognitive impairment. Nearly half of this severely obese study cohort exhibited measurable multidomain cognitive impairment. This was not dependent on NAFLD or another adiposity comorbidity.

Predicting overt hepatic encephalopathy after TIPS: Value of three minimal hepatic encephalopathy tests

Hepatic encephalopathy (HE) is a frequent and severe complication in patients after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for post-TIPS HE remain poorly defined. Minimal HE (mHE) is a well-known risk factor for overt HE in patients with cirrhosis without TIPS. We aimed to evaluate three tools frequently used for diagnosing mHE for their dynamic changes and their predictive value for overt HE after TIPS. We prospectively recruited 84 consecutive patients before TIPS insertion and monitored them for 180 days for post-TIPS HE. Before TIPS insertion, the patients underwent the portosystemic encephalopathy (PSE) syndrome test, the animal naming test (ANT), and the critical flicker frequency (CFF). Patients were retested after TIPS insertion. The majority of patients were male (67.9%), and the predominant indication for TIPS was refractory ascites (75%). Median age was 59 years, model for end-stage liver disease score was 12, and 66.3%, 64.6%, and 28.4% patients had evidence for mHE according to the PSE syndrome test, ANT, and CFF, respectively. Overall, 25 patients developed post-TIPS HE within 180 days after TIPS insertion. Post-TIPS incidence of overt HE was 22.2, 28.6, 45.5, and 55.6% in those with no, one, two, and three pathological tests at baseline, respectively. However, none of the three tests was significantly associated with post-TIPS HE. Of note, mean performance in all tests remained stable over time after TIPS insertion. PSE syndrome test, ANT and CFF, which are frequently used for diagnosing mHE have limited value for predicting HE after TIPS insertion. We could not find evidence that TIPS insertion leads to a psychometric decline in the long term. This prospective observational study compared three diagnostic tests for mHE and showed the limited value of these tests for predicting overt HE in patients with cirrhosis undergoing TIPS insertion. In addition, the results suggest that cognitive performance generally remains stable after TIPS insertion. These results are important for physicians and researchers involved in the management of patients with cirrhosis undergoing TIPS procedures. The study's findings serve as a starting point for further investigations on the development of more effective strategies for predicting and managing post-TIPS HE. ClinicalTrials.gov NCT04801290.

Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC)

PurposeThere is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). Patients and methodsFifty-one participants (PBC group – 38 patients, all patients but one Child-Pugh A; control group – 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. ResultsThe sGPV levels were higher in the PBC group compared to the controls: 36.07 ​± ​11.32 ​ng/mL vs 27.04 ​± ​11.72 ​ng/mL, p ​= ​0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83–58.83) sec. vs 45.90 (43.3–50.5) sec., p ​= ​0.0065. PPL levels were correlated with platelet count (rho ​= ​−0.46, p ​= ​0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. ConclusionsWe have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.

Validation of a Simple Quality-of-Life Score for Identification of Minimal and Prediction of Overt Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) is underdiagnosed because most clinics refrain from psychometric testing. Diagnostic activities need to go up so patients with MHE can get the treatment their condition requires. The sickness impact profile questionnaire for covert hepatic encephalopathy (SIPCHE) score is based on quality‐of‐life outcomes and has been proposed as a simple, patient‐administered diagnostic score for grade 1 and MHE. Validate the SIPCHE for MHE identification and overt hepatic encephalopathy (OHE) prediction. 110 patients with liver cirrhosis (age 60 years, Model for End‐Stage Liver Disease score of 11.4, 80% blue‐collar) provided information for SIPCHE scoring: gender, age, and four SIP statements: “I do not maintain balance (physically),” “I act irritable or impatient with myself,” “I am not doing any of the usual physical recreation or activities,” and “I am eating much less than usual.” MHE was diagnosed using an abnormal continuous reaction time test and/or portosystemic encephalopathy syndrome test score. Patients were followed for 2.7 years on average. SIPCHE score positivity had high sensitivity (82%) but low specificity (38%) for MHE detection. Patients with an abnormal SIPCHE had a higher incidence of OHE during follow‐up (35% vs. 14%, P = 0.05). OHE prediction sensitivity was 87% and exclusion sensitivity was 85%. The patients with an abnormal SIPCHE had twice as many subsequent episodes of OHE, and despite their high mortality, also a higher risk. An abnormal SIPCHE had a high sensitivity and low specificity for MHE identification. An abnormal SIPCHE was associated with a more than doubled risk of OHE, even with death as a competing event. SIPCHE could be used as a high‐sensitivity, low‐cost, surrogate marker of MHE in clinics without availability of psychometric tests and allow more patients to benefit from anti‐MHE treatment.

Prediction of overt hepatic encephalopathy by the continuous reaction time method and the portosystemic encephalopathy syndrome test in clinically mentally unimpaired patients with cirrhosis.

Predicting overt hepatic encephalopathy (OHE) is important because the condition is frequent, often requires hospitalization and is potentially preventable. The risk of OHE is related to pre-existing discrete cognitive defects, and for clinical practice it is recommended to apply two different psychometric tests to detect such deficits. We used the continuous reaction time test (CRT) and the portosystemic encephalopathy (PSE) syndrome test and examined their single and combined value for OHE prediction in cirrhosis patients. We studied 130 clinically mentally unimpaired cirrhosis patients by the two tests and followed them for an average of 38.5 months. The CRT measures velocity and stability of motor reaction times to 150 repeated auditory signals. The PSE is a five sub-set paper-and-pencil test battery evaluating cognitive and psychomotor processing, speed and vision-motor coordination. We collected data on episodes of OHE during follow-up. The clinical course was analysed in patient groups according to the outcome of each test and of both tests together. No anti-HE treatment was initiated except for cases with OHE. At baseline, the CRT test was abnormal in 74 patients and the PSE in 47. During follow-up 35 patients (27%) experienced 74 OHE events. 23 patients with abnormal CRT experienced OHE (prediction sensitivity 65%). The PSE predicted OHE in 14 patients (prediction sensitivity 40%). One or both tests were abnormal in 87/130 (67%) and this predicted OHE in 27 patients (21%) (prediction sensitivity 77%). The CRT test was clinically useful in identifying two-thirds of clinically mentally unimpaired cirrhosis patients who later experienced OHE, and the use of both the CRT and PSE showed satisfactory prediction by identifying three-fourths of later OHE cases.

Hepatic Encephalopathy Is Reversible in the Long Term After Liver Transplantation.

Cognitive dysfunction caused by hepatic encephalopathy (HE) improves within the first year after liver transplantation (LT). However, cognitive restitution seems to be incomplete in a subset of patients and after LT a new-onset cognitive decline was described. Data about the longterm development of cognitive function after liver transplantation (LT) are sparse. This prospective study analyzed whether a history of hepatic encephalopathy (HE) before LT had an impact on the longterm outcome of cognitive function after LT and if patients who underwent LT 5years earlier showed worse cognitive function than healthy controls. The cognitive function of 34 patients was assessed before LT and at 1year and 5years after LT by psychometric tests, including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the portosystemic encephalopathy syndrome test, which provides the psychometric hepatic encephalopathy score (PHES). Furthermore, patients completed surveys to assess health-related quality of life (HRQOL). An 22 additional patients were included after LT. Patients were subdivided by having a history of HE before LT. The control group consisted of 55 healthy patients adjusted for age and education. Before LT, patients performed significantly worse than controls in the psychometric tests: RBANS Total Scale (TS), mean±standard deviation (SD), 92.6±13.3 versus 99.9±12.0, P=0.01; and PHES, median (interquartile range [IQR]), 0 (-3 to 1) versus 1 (0-2), P<0.001. At 1year after LT, patients with a history of HE still showed cognitive impairment compared with controls: RBANS TS, mean±SD, 89.8±15.1 versus 99.9±12.0, P<0.01; and PHES, median (IQR), 0 (-2 to 1.25) versus 1 (0-2), P=0.03. At 5years after LT, patients with and without a history of HE showed normal cognitive function and improved HRQOL. In conclusion, HE-associated cognitive impairment seems to be reversible within 5years after LT.

P: 58 Prediction of Overt Hepatic Encephalopathy by the Continuous Reaction Time Method and the Portosystemic Encephalopathy Syndrome Test in Patients With Cirrhosis

BACKGROUND: Predicting overt hepatic encephalopathy (OHE) is of major importance because the condition is unpleasant, requires hospitalization, and partly preventable. The risk is related to pre-existing discrete cognitive defects, and a number of psychometric tests are validated for detection of such defects. For clinical practice it is recommended to apply two different tests. We used the Continuous Reaction Time test (CRT) and the Porto Systemic Encephalopathy Test (PSE), and examined their single and combined value for prediction of OHE in cirrhosis patients. METHODS: We studied 130 mentally unimpaired cirrhosis patients by the two tests and followed them up for on average 38.5 months. The CRT measures velocity and stability in motor reaction times to 150 repeated auditory. The PSE is a paper-and-pencil test measuring the duration of completing 5 tasks. We collected data on episodes of OHE during follow-up. The clinical course was analysed in patient groups according to the outcome of each test and of both tests together. No anti-HE treatment was initiated except for OHE. RESULTS: We observed 74 OHE events. The PHES was abnormal in 47 and predicted 31 OHE episodes among 14 patients (PPV = 29%, NPV of 75%, sens. 40%, spec. 65%). The CRT test was abnormal in 74/130 and predicted 54 OHE episodes among 23 patients (PPV = 31%, NPV = 78%, sens. 65%, spec. 46%). One or both tests were abnormal in 87/130 and predicted 60 OHE episodes among 27 patients (PPV = 31%, NPV = 81%, sens. 77%, spec. 40%). 43/130 had two normal tests but 8 experienced OHE and had 14 OHE-admissions. CONCLUSIONS: The combined use of PSE and CRT test identified 77% of patients who later experienced OHE while ruling out future OHE with an NPV of 81%.

Validation of the Korean Stroop Test in Diagnosis of Minimal Hepatic Encephalopathy

The burden of minimal hepatic encephalopathy (MHE) is significant, but no universal criteria for diagnosis have been established. We aimed to validate the Korean Stroop Test for MHE screening. Chronic hepatitis B-related liver cirrhosis patients were recruited prospectively from 13 centers. The Korean Stroop Test consisted of two Stroop-off states (color and word) and two Stroop-on states (inhibition and switching). Accuracy adjusted psychomotor speed (rate correct score) of these tests were analyzed. Sex- and age- adjusted rate correct scores of these tests were rated as the Korean Stroop Score (K-Stroop score). MHE was diagnosed when Portosystemic Encephalopathy Syndrome Test (PHES) scores were below −4. A total of 220 liver cirrhosis patients and 376 healthy controls were enrolled. Prevalence of MHE was 20.6% in cirrhosis patients. Rate correct scores and the K-Stroop score showed significant differences between healthy controls, cirrhosis patients without MHE, and cirrhosis patients with MHE. The rate correct score of the K-Stroop score was 0.74 (95% Confidence Interval: 0.66–0.83, P < 0.001). Female gender and the K-Stroop score were significant for MHE diagnosis. The Korean Stroop Test is simple and valid for screening of MHE.

Covert hepatic encephalopathy leads to distinct alterations in the emotional state, independently of MELD-Score.

Covert hepatic encephalopathy impairs many aspects of quality of life, although its impact on the emotional state has not been evaluated. This study aims to evaluate the impact of covert hepatic encephalopathy on the emotional state and which factors are associated with changes in the emotional state in patients with cirrhosis. This single-center study included all patients with cirrhosis who underwent the portosystemic encephalopathy syndrome (PSE) test, critical flicker frequency, and emotional state assessment with the Eigenschaftswörterliste 60-S in 2011. Covert hepatic encephalopathy was defined by abnormal PSE. Parametric and non-parametric tests were used according to variable distribution. One hundred seventeen patients with cirrhosis were included (median age: 59 [interquartile range: 48 - 67], 32 %female, 74 % alcohol-associated). Seventy patients had covert hepatic encephalopathy (60 %) with a higher MELD (16[interquartile range: 13 - 21], p = 0.001) and a higher Child-Pugh score (p = 0.003) compared to patients without encephalopathy. Patients with covert encephalopathy felt reduced mental activity (p = 0.004), lower general well-being (p = 0.001), and reduced extraversion (p = 0.021). The scores in the negative domains such as general lethargy (p = 0.031) and anxiousness/depressiveness (p = 0.033) were higher in patients with covert hepatic encephalopathy. There was no correlation between MELD and the emotional state. Patients with 2 pathological tests (critical flicker frequency and PSE) showed the most distinct alterations in the emotional state in the group of patients with covert hepatic encephalopathy. Patients with covert hepatic encephalopathy have an alteration of the emotional state, which is more marked in patients with 2 pathological tests. Interestingly, MELD had no impact on the emotional state.

Critical flicker frequency: A useful tool in diagnosis of minimal hepatic encephalopathy

Background: Minimal hepatic encephalopathy (MHE) is viewed as mild neuro-cognitive abnormalities in cirrhotics without overt encephalopathy. Diagnostic strategies for MHE include portosystemic encephalopathy (PSE) syndrome test, critical flicker frequency test (CFF), computerised tests like Inhibitory control test, Scan test etc. We compared critical flicker frequency test with standard PSE syndrome test. Methods: Fifty patients with cirrhotics of liver without overt encephalopathy were studied. PSE syndrome test was done with the standard charts. PSE score was calculated from the normal distribution tables. CFF was tested with manual CFF tool. Results: Their mean age (years) was 46 ± 12.8; there were 45 males. Of these 22, 21 and 7 patients belonged to Child's A, B and C categories. PSE score detected MHE in 40%, of which 35% were in Child's A and 65% in Child's B/C. CFF was normal (>39HZ) in 36% patients and abnormal ( Conclusions: CFF test is highly sensitive (85%) with high negative predictive value (85%). It is a useful test to rule out MHE. The test is simple, quick and in-expensive and can be performed in the outpatient settings.

Stepwise diagnosis in covert hepatic encephalopathy: critical flicker frequency and MELD-score as a first-step approach.

The diagnosis of covert hepatic encephalopathy (CHE) by means of portosystemic encephalopathy syndrome (PSE) test is costly and therefore infrequently performed. To determine the ability of critical flicker frequency (CFF) alone or in combination with laboratory findings, as an initial test to pre-select which patients should undergo further testing for the diagnosis of covert hepatic encephalopathy. This single-centre study included all patients with cirrhosis who underwent PSE and CFF in 2011. CHE was defined by abnormal PSE test. Logistic regression analysis was performed to identify predictors of CHE. ROC curves were used to identify cut-offs of these independent predictors. One hundred and seventeen patients were included. Seventy (60%) had CHE with a higher MELD [16 (IQR 13-21); P=0.001] and lower CFF [38Hz (IQR 36-41) P=0.0011]. On multivariate analyses, CFF [OR 0.83 (95% CI 0.74-0.94)] and MELD [OR 1.13 (95% CI 1.04-1.22)] were identified as independent predictors of CHE. Sensitivity and specificity of a CFF cut-off of 43Hz was 93.5% and 42.9%, and for a MELD cut-off of 24, it was 97.5% and 32.8% respectively. Most patients with a MELD-Score <24 and a CFF >43Hz did not have CHE (78%) and with a MELD-Score >24 and CFF <43Hz most patients had CHE (85%). Therefore, 27% of patients could avoid further testing with a diagnostic accuracy of 81%. The combination of MELD-score and critical flicker frequency may be used as a first diagnostic step to filter patients, in whom further covert hepatic encephalopathy testing could be avoided.

Treatment with a potassium–iron–phosphate–citrate complex improves PSE scores and quality of life in patients with minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is one of the possible complications of liver cirrhosis. In this study, a potassium-iron-phosphate-citrate complex was analyzed for its efficacy and safety in the treatment of MHE, as this complex is supposed to bind to the major pathogenic factor of MHE: intestinal ammonia. In this placebo-controlled, double-blind clinical trial, 51 patients with MHE were randomized into two groups at a ratio of 1 : 1 and treated for 4 weeks either with a potassium-iron-phosphate-citrate complex or a placebo. The efficacy of treatment was assessed according to changes in the portosystemic encephalopathy (PSE) score. Further assessments included alterations in quality of life and safety evaluations. Significantly more patients showed improvements in the PSE syndrome test from pathological to nonpathological PSE scores in the potassium-iron-phosphate-citrate-treated group (72.0%) than in the placebo group (26.9%; P=0.0014). Furthermore, quality of life improved at a higher grade in the verum group (by 0.7 ± 0.6 U) compared with the placebo group (by 0.2 ± 0.6 U; P=0.0036). Adverse events occurring in 28.0% of potassium-iron-phosphate-citrate-treated patients were generally mild or moderate and affected mainly the gastrointestinal tract. Treatment with potassium-iron-phosphate-citrate significantly improved PSE scores and quality of life in patients with MHE. The potassium-iron-phosphate-citrate complex is a well-tolerated treatment option in MHE.

Comparison of the most favoured methods for the diagnosis of hepatic encephalopathy in liver transplantation candidates

ObjectiveHepatic encephalopathy (HE) is a common complication of liver insufficiency. While there is widespread acceptance of its importance, there is no consensus on how best to diagnose and monitor HE.ObjectiveTo...

Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy

Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy

Assessment of low-grade hepatic encephalopathy: A critical analysis

The value of paper-pencil tests and West-Haven-criteria for assessment of low-grade hepatic encephalopathy under conditions of a randomized, double-blind, placebo-controlled, clinical trial was evaluated in a cohort of 217 cirrhotics. Patients were graded at least twice clinically for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery. Re-evaluation of the study documentation showed that at study entry 33% and during the study even 50% of the patients were wrongly allocated to minimal or overt hepatic encephalopathy. Despite the participating physicians' training, 31% of the number-connection-tests-A, 20% of the number-connection-tests-B and 28% of the line-tracing-test were in retrospect considered invalid by an independent psychologist. Neither the Portosystemic-Encephalopathy-Syndrome (PSE) test nor the Psychometric-Hepatic-Encephalopathy-Sum (PHES)-score reliably picked up clinical improvement in the individual patient. Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy, the clinical classification of individual patients into one of the groups will have a high rate of error. The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test. Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven-criteria and paper-pencil tests including related scores for quantification of low-grade HE at least in multicenter approaches.