• Ammonia
• Bibliometric analysis
• Gut microbiota
• Hepatic encephalopathy
• Liver cirrhosis
• Sarcopenia

• Humans
• Hepatic Encephalopathy/diagnosis
• Male
• Female
• Middle Aged
• Prospective Studies
• Aged
• Predictive Value of Tests
• Neuropsychological Tests
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/complications
• Psychometrics/methods
• Adult
• Prognosis
• Severity of Illness Index

• Stroop test
• cirrhosis
• minimal hepatic encephalopathy
• quality of life

• National Natural Science Foundation of China

• Critical flicker frequency
• EncephalApp
• Health apps
• Minimal hepatic encephalopathy
• Psychometric hepatic encephalopathy score
• Stroop test

• Humans
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/complications
• Male
• Liver Cirrhosis/complications
• Female
• Middle Aged
• Prospective Studies
• Psychometrics
• Neuropsychological Tests
• Aged
• Adult
• ROC Curve
• Severity of Illness Index
• Sensitivity and Specificity

• Neurochemistry/history
• History, 20th Century
• History, 21st Century
• Humans

• Liver cirrhosis
• advanced chronic liver disease
• compensated cirrhosis
• decompensated cirrhosis
• hepatic encephalopathy
• palliative care
• portal hypertension
• recompensated cirrhosis

• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Palliative Care
• Hepatic Encephalopathy/therapy
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/diagnosis
• Hypertension, Portal/therapy
• Hypertension, Portal/etiology
• Hypertension, Portal/diagnosis
• Disease Progression
• Liver Function Tests

• Clinical manifestations
• Hepatic encephalopathy
• West Haven

• Humans
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/therapy
• Liver Cirrhosis/complications
• Severity of Illness Index
• Liver Diseases/complications
• Cognition

• Cirrhosis
• Medical apps
• Subclinical hepatic encephalopathy
• Tool
• West Haven Criteria

• Humans
• Female
• Adult
• Middle Aged
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/epidemiology
• Cross-Sectional Studies
• Prospective Studies
• Stroop Test
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis

• bacterial translocation
• end-stage liver disease
• genetic risk factor
• immune response
• liver insufficiency
• portal hypertension

• Female
• Humans
• Male
• Middle Aged
• Ammonia
• Bacterial Translocation
• Hepatic Encephalopathy/complications
• Inflammation
• Lipopolysaccharide Receptors
• Liver Cirrhosis/complications
• Nod2 Signaling Adaptor Protein/genetics
• Prospective Studies

• Dr. Rolf M Schwiete Stiftung

• TIPS
• cirrhosis
• hepatic encephalopathy

• TIPS
• ammonia
• cirrhosis
• hepatic encephalopathy
• liver transplantation

• Humans
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/therapy
• Portasystemic Shunt, Transjugular Intrahepatic/adverse effects
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Risk Factors
• Prognosis
• Treatment Outcome

• Thai norms
• animal naming test
• cirrhosis
• minimal hepatic encephalopathy
• psychometric hepatic encephalopathy score

• GRU 6105530009-1 Chulalongkorn University
• RA 65/021 Chulalongkorn University
• HEA663000044 Chulalongkorn University
• Thai Red Cross Society

• Covert hepatic encephalopathy
• Liver cirrhosis
• Randomized prospective study
• Rifaximin
• Single-center open-label study

• antibiotic therapy
• hepatic encephalopathy
• liver cirrhosis

• Norgine

• Diagnostic tests
• Hepatic encephalopathy
• Liver cirrhosis
• Psychometric tests
• Test validation

• Cognitive Dysfunction/complications
• Hepatic Encephalopathy
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Psychometrics/methods
• Quality of Life

A simple, accurate and fast method was developed for the assessment of 3-nitrotyrosine as a biomarker for the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) using a (Eu(TTA)₃Phen) photo probe. 3-Nitrotyrosine can remarkably quench the luminescence intensity of the (Eu(TTA)₃Phen) complex in DMSO at pH = 9 and λ_em = 617 nm. The quenching of the luminescence intensity of (Eu(TTA)₃Phen) complex particularly the electrical emission band at λ_em = 617 nm is used for the assessment of 3-nitrotyrosine in different serum samples of patients with liver cirrhosis.

A simple, accurate and fast method was developed for the assessment of 3-nitrotyrosine as a biomarker for the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) using a (Eu(TTA)₃Phen) photo probe.

• Cirrhosis
• Critical flicker frequency
• Minimal hepatic encephalopathy
• Portosystemic hepatic encephalopathy score
• Turkish norms

• Hepatic Encephalopathy/diagnosis
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Male
• Psychometrics
• Severity of Illness Index
• Turkey/epidemiology

• efficacy
• hepatic encephalopathy
• meta-analysis
• rifaximin
• safety

• ammonia
• critical flicker frequency
• diagnosis
• inhibitory control test
• liver cirrhosis
• minimal hepatic encephalopathy
• overt
• psychometric hepatic encephalopathy score
• psychometric tests
• serum 3-nitrotyrosine levels

• MR spectroscopy
• astrocytes
• neurophysiology
• oscillatory activity
• osmotic and oxidative stress
• transcranial magnetic stimulation

• Hepatic Encephalopathy/metabolism
• Humans
• Animals
• Ammonia/metabolism
• Oxidative Stress

• animal naming test.
• critical flicker frequency
• hepatic vascular malformation
• portosystemic shunt

• Cross-Sectional Studies
• Hepatic Encephalopathy/drug therapy
• Humans
• Liver Diseases
• Telangiectasia, Hereditary Hemorrhagic/complications

• NAFL
• NAFLD
• NASH
• neurological impairment
• psychometric score

• SAF2017-82917-R Ministerio de Ciencia e Innovación Spain
• FIS PI18/00150 Instituto de Salud Carlos III, Spain
• Fundación Ramón Areces Fundación Ramón Areces
• PROMETEOII/2018/051 Consellería Educación Generalitat Valenciana
• FIS PI18/00150; PROMETEOII/2018/051 cofunded with European Regional Development Funds
• GRISOLIAP/2019/003; ACIF/2018/284, ACIF/2019/232 Pre-doctoral contracts from Generalitat Valenciana
• CM19/00011 Rio-Hortega contract from Instituto de Salud Carlos III

Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.

• Minimal hepatic encephalopathy
• Sarcopenia
• Probiotics
• Non-absorbable disaccharides, Rifaximin
• L-ornithine-L-aspartate

• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/therapy
• Humans
• Lactulose/therapeutic use
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/therapy
• Quality of Life
• Rifaximin/therapeutic use

• Ammonemia
• Cirrhosis
• Hepatic encephalopathy
• Minimal hepatic encephalopathy
• Transjugular intrahepatic portosystemic shunt

• Hepatic Encephalopathy/diagnosis
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Reflex, Acoustic

Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES).

To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD.

This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < −4 for PHES. All participants were also screened for cognitive function and depression.

Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy.

It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.

• Critical flicker frequency
• cerebral dysfunction
• chronic kidney failure
• uremia
• uremic encephalopathy

Minimal hepatic encephalopathy (MHE) is a common complication of liver cirrhosis not only leading to a decrease in the quality of life, but also predicting development of overt encephalopathy. The diagnosis of MHE usually relies on a combination of neuropsychological tests, while robust serum biomarkers are lacking. We aimed to assess serum concentrations of brain-derived neurotrophic factor (BDNF) in MHE patients.

Serum BDNF was assessed in 78 patients with liver cirrhosis (53 male, median age 55 years) and 40 healthy individuals. 43 subjects underwent extensive evaluation for MHE by psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT) or critical flicker frequency (CFF).

Serum BDNF was twofold lower in liver cirrhosis compared to healthy subjects [13.6 (7.8-22.6) vs. 33.0 (24.1-40.7) ng/ml, p < 0.001] and its decrease reflected a degree of liver insufficiency assessed by model for end-stage liver disease (MELD). BDNF showed a negative correlation with bilirubin (R = –0.35, p = 0.005) and international normalized ratio (INR) (R = –0.37, p = 0.003), and positive with platelets (PLT) (R = 0.36, p = 0.004), while no associations with age, sex, body mass index (BMI), waist-hip ratio (WHR), creatinine and ammonia were noted. Importantly, subjects with a diagnosis of MHE by at least two modalities showed the lowest levels of BDNF [10.9 (2.5-14.4) vs. 19.9 (9.3-29.4) ng/ml, p < 0.01]. Patients with self-reported sleep disturbances had significantly lower serum BDNF [13.0 (2.5-23.4) vs. 20.0 (8.4-31.3) ng/ml, p = 0.04].

The lowest serum BDNF concentration was noted in patients with MHE and sleep disturbances, which suggests a role in pathophysiology of hepatic encephalopathy but also as a potential biomarker.

• BDNF
• ICT
• PHES
• liver cirrhosis
• minimal hepatic encephalopathy

Type C hepatic encephalopathy (HE) is a brain dysfunction caused by severe hepatocellular failure or presence of portal-systemic shunts in patients with liver cirrhosis. In its subclinical form, called “minimal hepatic encephalopathy (MHE), only psychometric tests or electrophysiological evaluation can reveal alterations in attention, working memory, psychomotor speed and visuospatial ability, while clinical neurological signs are lacking. The term “covert” (CHE) has been recently used to unify MHE and Grade I HE in order to refer to a condition that is not unapparent but also non overt. “Overt” HE (OHE) is characterized by personality changes, progressive disorientation in time and space, acute confusional state, stupor and coma. Based on its time course, OHE can be divided in Episodic, Recurrent or Persistent. Episodic HE is generally triggered by one or more precipitant factors that should be found and treated. Unlike MHE, clinical examination and clinical decision are crucial for OHE diagnosis and West Haven criteria are widely used to assess the severity of neurological dysfunction. Primary prophylaxis of OHE is indicated only in the patient with gastrointestinal bleeding using non-absorbable antibiotics (Rifaximin) or non-absorbable disaccharides (Lactulose). Treatment of OHE is based on the identification and correction of precipitating factors and starting empirical ammonia-lowering treatment with Rifaximin and Lactulose (per os and enemas). The latter should be used for secondary prophylaxis, adding Rifaximin if HE becomes recurrent. In recurrent/persistent HE, the treatment options include fecal transplantation, TIPS revision and closure of eventual splenorenal shunts. Treatment of MHE should be individualized on a case-by-case basis.

• Spontaneous Portal-systemic Shunts
• cirrhosis
• hepatic encephalopathy
• minimal hepatic encephalopathy
• rifaximin, non-absorbable disaccharides
• transjugular intrahepatic portosystemic shunt

• Ammonia
• Diagnosis
• Hepatic encephalopathy
• Management
• Pathogenesis
• Pathophysiology
• Treatments

• Cost of Illness
• Disease Management
• Hepatic Encephalopathy/classification
• Hepatic Encephalopathy/physiopathology
• Hepatic Encephalopathy/psychology
• Hepatic Encephalopathy/therapy
• Humans
• Kidney Failure, Chronic/complications

• Department of Health

• cirrhosis
• complications
• hepatic encephalopathy
• spontaneous portosystemic shunts

Early detection and evaluation of cognitive alteration in chronic liver disease is important for predicting the subsequent development of hepatic encephalopathy. While visuomotor tasks have been rigorously employed for cognitive evaluation in chronic liver disease, there is a paucity of auditory processing task. Here we focused on auditory perception and examined behavioral and haemodynamic responses to a melodic contour identification task (CIT) to compare cognitive abilities in patients with chronic liver disease (CLD, N = 30) and healthy controls (N = 25). Further, we used support vector machines to examine the optimal combination of channels of functional near-infrared spectroscopy that can classify cognitive alterations in CLD. Behavioral findings showed that CIT performance was significantly worse in the patient group and CIT significantly correlated with neurocognitive evaluation (i.e., number connection test, digit span test). The findings indicated that CIT can measure auditory cognitive capacity and its difference existing between patient group and healthy controls. Additionally, optimal subsets classified the 16-dimensional haemodynamic data with 78.35% classification accuracy, yielding markers of cognitive alterations in the prefrontal regions (CH6, CH7, CH10, CH13, CH14, and CH16). The results confirmed the potential use of behavioral as well as haemodynamic responses to music perception as an alternative or supplementary method for evaluating cognitive alterations in chronic liver disease.

Minimal hepatic encephalopathy (MHE) is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting, which results in a wide range of cognitive deficits including impairments in working attention, psychomotor speed, and executive function. Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE. Most high-risk cirrhotic patients are required to be examined; however, paper-and-pencil psychometric tests are neither convenient nor rapid to perform in the clinic. Recently, novel computerized psychometric tests, including the inhibitory control test, EncephalApp Stroop App, and critical flicker frequency, have been proven to be rapid, effective, and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations. However, diagnostic accuracy of these tests is influenced by educational background, age, and cultural differences. This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.

• Minimal hepatic encephalopathy
• Diagnosis
• Psychometric test
• Inhibitory control test
• EncephalApp Stroop App
• Critical flicker frequency

To evaluate the effects of l-carnitine on impaired brain function in patients with liver cirrhosis. We conducted a retrospective cohort study that included sequential 80 liver cirrhosis patients with impaired brain function evaluated using near-infrared spectroscopy (NIRS). Among them, l-carnitine was administered to 48 patients. The NIRS data and blood ammonia level at baseline and after 8 weeks of treatment were compared between patients administered with l-carnitine (l-carnitine group) and those who were not (control group). The NIRS data at baseline were similar between the l-carnitine and control groups (0.04 ± 0.04 vs. 0.04 ± 0.05 mMmm, p = n.s), whereas those in the l-carnitine group (n = 48) were significantly better than that of the control group at 8 weeks of treatment (n = 32) (0.103 ± 0.081 vs. 0.040 ± 0.048 mMmm, p < 0.001). In the l-carnitine group, 35.4% (17/48) of patients had hyperammonemia. The NIRS data of the l-carnitine group at 8 weeks of treatment were significantly improved than that of the control group, irrespective of baseline ammonia levels (0.11 ± 0.09 vs. 0.04 ± 0.05 mMmm, p = 0.005, and 0.10 ± 0.06 vs. 0.02 ± 0.03 mMmm, p = 0.003, for normal baseline ammonia and elevated ammonia levels, respectively). In the multivariate analysis, l-carnitine administration (odds ratio [OR] 3.51, 95% confidence interval [CI] 1.23–9.99, p = 0.019) and baseline NIRS data of ≤ 0.07 mMmm (OR 5.21, 95% CI 1.69–16.0, p = 0.0041) were found as independent significant factors. l-carnitine improves impaired brain function in patients with liver cirrhosis.

• Critical flicker frequency
• Direct-acting antivirals
• HCV
• MHE

Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encepha-lopathy (HE). We compared the usefulness of the Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) for the diagnosis of MHE and the prediction of the development of overt episodes of HE.

103 consecutive patients with liver cirrhosis without overt HE were subjected to PHES and ANT evaluation. The receiver-operating characteristic curve was used to determine the optimum cut-off of the ANT value for the diagnosis of MHE.

Thirty-seven (35.9%) patients had MHE as assessed by altered PHES. ANT (< 14) was positive in 36 (34.95%) patients with MHE with a sensitivity of 89.19% and specificity of 95.7%, positive predictive value (PPV) of 91.67%, negative predictive value (NPV) of 94.03% and diagnostic accuracy of 93.20%. The area under the curve for diagnosis of MHE was 0.978 (95% CI: 0.954-1.0). MHE patients had significantly lower ANT as compared to non-MHE patients and controls (10.81 ±0.324 vs. 15.27 ±0.147 vs. 15.78 ±0.192, respectively, p = 0.01). ANT correlated with PHES (r = 0.752, p = 0.001) and also with Child-Pugh (r = –0.408, p = 0.001) and MELD (r = –0.318, p = 0.001) scores. During follow-up, 14 patients in the MHE group and 4 in the non-MHE group developed overt episodes of HE (p = 0.001).

ANT is simple and accurate for the diagnosis of MHE and prediction of overt episodes of HE in patients with cirrhosis and correlates well with the Child-Pugh and MELD scores.

• cirrhosis
• hepatic encephalopathy
• minimal hepatic encephalopathy

• Ammonia/metabolism
• Automobile Driving
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/metabolism
• Hepatic Encephalopathy/physiopathology
• Hepatic Encephalopathy/therapy
• Humans
• Nutritional Support
• Patient Reported Outcome Measures
• Prognosis
• Societies, Medical