Tabla de la normalidad de las pruebas psicométricas para el diagnóstico de encefalopatía hepática subclínica en la población Dominicana / Score of normality psychometric tests for the diagnosis of subclinical hepatic encephalopathy in the Dominican Population

Introducción: La encefalopatía hepática mínima (EHM), es una enfermedad definida por la existencia de varias alteraciones neurofisiológicas, indetectables a la exploración neurológica y el examen clínico. Dentro de las estrategias diagnosticas para la EHM se contemplan las pruebas psicométricas (PHE), pero para su aplicación es indispensable la estandarización previamente en la población de estudio. Objetivo: El estudio se propuso determinar la tabla de la normalidad de las PHE para diagnosticar la encefalopatía hepática subclínica en una muestra de la población dominicana. Método: Se realizó un estudio descriptivo, prospectivo y transversal en un hospital de referencia nacional. Se analizaron 134 personas clasificados por grupos de edades (18-70 años de edad) y años de escolaridad. Se diseñó una tabla de 5x5. Se estudió la influencia de la edad, sexo, uso de espejuelo y de los años de escolarización en el rendimiento de cada uno de las PHE, para lo cual se utilizaron las siguientes pruebas estadísticas: análisis de varianza (ANOVA), prueba t de Student y regresión lineal. Resultado: La escolaridad y la edad fueron variables determinantes en el desempeño de las 5 pruebas psicométricas. Pero, la correlación univariable de la edad con el desempeño de la prueba TMS no hubo diferencias intra e inter grupos estadísticamente significativas (p>0.171). Conclusión: se confecciono la fórmula de predicción de resultados de los test psicométricos. Ninguno sobrepasó el punto de corte de la puntuación que oscila entre los -4 y los +2 puntos.

Introduction: Minimal hepatic encephalopathy (MHE) is a disease defined by the existence of several neurophysiological alterations, undetectable by neurological examination and clinical examination. Among the diagnostic strategies for EHM, psychometric tests (PHE) are contemplated, but for their application, prior standardization in the study population is essential. Objective: The study will need to determine the normality table of PHE to detect subclinical hepatic encephalopathy in a sample of the Dominican population. Method: A descriptive, prospective and cross-sectional study was carried out in a national reference hospital. 134 people classified by age groups (18-70 years of age) and years of schooling were analyzed. A 5x5 board is recommended. The influence of age, sex, use of glasses and years of schooling on the performance of each one of the PHEs was studied, for which the following statistical tests were used: analysis of variance (ANOVA), Student's t test and linear regression. Result: Schooling and age were determining variables in the performance of the 5 psychometric tests. But, the univariate coincidence of age with the performance of the TMS test, there were no statistically significant intra and inter group differences (p>0.171). Conclusion: the formula for predicting the results of the psychometric tests was made. None exceeded the cut-off point of the score that oscillates between -4 and +2 points.

Manganese Associated with Non-Wilsonian Hepatolenticular Degeneration as a Rare Cause of Encephalopathy: Case Report

Aim: To describe the clinical picture, diagnosis, and treatment of a patient with encephalopathy as a manifestation of manganese-induced non-Wilsonian hepatolenticular degeneration (NWHD) in a high-complexity care center in a Latin American country. Case description: A 55-year-old male patient from the United States with a history of liver disease associated with alcohol consumption was admitted to the emergency department due to diarrhea, hematemesis, and psychomotor agitation. During his stay, his state of consciousness deteriorated, requiring orotracheal intubation. In his diagnostic study, cerebrospinal fluid tests were negative for infectious etiologies; the endoscopic examinations showed no marks of portal hypertension bleeding, while ammonium and tests for metabolic causes were normal. However, areas of hyperintensity in the basal ganglia were documented on brain MRI, with normal ceruloplasmin serum and urine copper levels, which ruled out Wilson's disease and determined the diagnosis of manganese-induced NWHD. Conclusion: NWHD is a rare cause of chronic encephalopathy with clinical manifestations of extrapyramidal symptoms secondary to basal ganglia dysfunction due to severe liver disease. Its diagnosis becomes a challenge, given that manganese deposits produce it, and no biomarkers can establish the level of exposure to this metal. Brain MRI is indispensable in reflecting these deposits in the basal ganglia.

Objetivo: Describir la presentación clínica, el diagnóstico y el tratamiento de un paciente con encefalopatía como manifestación de degeneración hepatolenticular no wilsoniana producida por manganeso, en un centro de alta complejidad de un país latinoamericano. Descripción del caso: Paciente masculino de 55 años, procedente de Estados Unidos, con antecedente de enfermedad hepática asociada con consumo de alcohol, quien ingresó al servicio de urgencias por un cuadro de diarrea, hematemesis y agitación psicomotora. Durante la estancia presentó deterioro en el estado de consciencia, por lo que requirió intubación orotraqueal. En su estudio diagnóstico, las pruebas de líquido cefalorraquídeo fueron negativas para etiologías infecciosas, en los estudios endoscópicos no tenía estigmas de sangrado portal hipertensivo y el amonio y los estudios para causas metabólicas fueron normales. Sin embargo, se documentaron áreas de hiperintensidad en los ganglios de la base en la resonancia magnética cerebral, con niveles de ceruloplasmina sérica y cobre urinario normales, lo que descartó enfermedad de Wilson y definió el diagnóstico de degeneración hepatolenticular no wilsoniana por depósitos de manganeso. Conclusión: La degeneración hepatolenticular no wilsoniana es una causa infrecuente de encefalopatía crónica con manifestaciones clínicas de extrapiramidalismo, secundaria a disfunción de los ganglios de la base por enfermedad hepática grave. Su diagnóstico se convierte en un reto, dado que se produce por depósitos de manganeso y no existen biomarcadores que puedan establecer el nivel de exposición a este metal. La resonancia magnética cerebral juega, por tanto, un papel indispensable al reflejar esos depósitos en los ganglios de la base.

Anti-inflammatory strategies for hepatic encephalopathy: preclinical studies / Estratégias anti-inflamatórias para encefalopatia hepática: estudos pré-clínicos

Abstract Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome. Often, HE causes cognitive and motor dysfunctions due to an acute or chronic insufficiency of the liver or a shunting between the hepatic portal vein and systemic vasculature. Liver damage induces peripheral changes, such as in the metabolism and peripheral inflammatory responses that trigger exacerbated neuroinflammation. In experimental models, anti-inflammatory strategies have demonstrated neuroprotective effects, leading to a reduction in HE-related cognitive and motor impairments. In this scenario, a growing body of evidence has shown that peripheral and central nervous system inflammation are promising preclinical targets. In this review, we performed an overview of FDA-approved drugs and natural compounds which are used in the treatment of other neurological and nonneurological diseases that have played a neuroprotective role in experimental HE, at least in part, through anti-inflammatory mechanisms. Despite the exciting results from animal models, the available data should be critically interpreted, highlighting the importance of translating the findings for clinical essays.

Resumo A encefalopatia hepática (EH) é uma síndrome neuropsiquiátrica potencialmente reversível. Muitas vezes a EH causa disfunções cognitivas e motoras devido à insuficiência do fígado ou por um desvio entre a veia porta hepática e a vasculatura sistêmica. O dano no fígado provoca alterações periféricas, como no metabolismo e nas respostas inflamatórias periféricas, que desencadeiam uma neuroinflamação exacerbada. Em modelos experimentais, estratégias anti-inflamatórias têm demonstrado efeitos neuroprotetores, levando a uma redução dos prejuízos cognitivos e motores relacionados à EH. Neste cenário, evidências crescentes têm mostrado a inflamação periférica e no sistema nervoso central como um promissor alvo pré-clínico. Nesta revisão, abordamos uma visão geral de drogas e compostos naturais aprovados pelo FDA para o uso no tratamento de outras doenças neurológicas e não neurológicas, que tiveram papel neuroprotetor na EH experimental, pelo menos em parte, através de mecanismos anti-inflamatórios. Apesar dos resultados empolgantes em modelos animais, os dados avaliados devem ser criticamente interpretados, destacando a importância da tradução dos achados para ensaios clínicos.

Research advances in brain lactate level and hepatic encephalopathy / 临床肝胆病杂志

Hepatic encephalopathy (HE) is a common complication and an independent risk factor for death in patients with liver cirrhosis. Brain lactate level is associated with the progression and severity of HE, and research on brain lactate level may help to further explain the pathogenesis of HE. This article summarizes the metabolic process of brain lactate, the association between brain lactate level and HE, and the potential therapeutic targets for HE and provides a reference for clinicians to further systematically evaluate the progression, treatment outcome, and prognosis of patients with HE, in order to reduce the medical burden of patients and improve the prognosis of patients with HE.

Research advances in the association between sarcopenia and hepatic encephalopathy in patients with liver cirrhosis / 临床肝胆病杂志

Sarcopenia is one of the manifestations of malnutrition in patients with liver cirrhosis. Most studies have shown that sarcopenia is associated with overt hepatic encephalopathy (OHE), leading to an increased risk of events such as reduced quality of life, poor clinical prognosis, and even death in patients with liver cirrhosis, but there are few studies on the association between sarcopenia and minimal hepatic encephalopathy (MHE). This article reviews the research advances in sarcopenia and hepatic encephalopathy to provide a reliable basis for clinical treatment, and it is pointed out that the nutritional status of patients can be improved to prevent MHE and even reduce the onset of OHE, thereby improving patient prognosis, increasing quality of life, and reducing the risk of death.

Predictive value of controlled nutritional status score for overt hepatic encephalopathy after transjugular intrahepatic portosystemic stent-shunt of Budd-Chiari syndrome / 中华消化外科杂志

Objective:To investigate the predictive value of controlled nutritional status (CONUT) score for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosys-temic stent-shunt (TIPSS) in Budd-Chiari syndrome patients.Method:The retrospective case-control study was conducted. The clinicopathological data of 48 Budd-Chiari syndrome patients who underwent TIPSS in the First Affiliated Hospital of Zhengzhou University from August 2014 to March 2021 were collected. There were 26 males and 22 females, aged (46±13)years. Observation indicators: (1) surgical situations and follow-up; (2) analysis of influencing factors of OHE after TIPSS; (3) predic-tion of OHE after TIPSS. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed using the t test. Measurement data with skewed distribution were represented by M( Q1, Q3), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Multivariate analysis was performed using the Logistic regression model with forward method. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the efficacy. Comparison among AUC was performed using the Delong test. Results:(1) Surgical situations and follow-up. All 48 patients underwent TIPSS successfully, and the operation time of the 48 patients was (131±29)minutes. All patients were implanted with 8 mm covered stent. All 48 patients were followed up for 46(25,71)months, and there were 14 cases with OHE and 34 cases without OHE after TIPSS. Of the 14 cases with OHE, 12 cases were evaluated as West-Haven Ⅱ grade and 2 cases were evaluated as West-Haven Ⅲ grade. (2) Analysis of influencing factors of OHE after TIPSS. Results of multivariate analysis showed that history of hepatic encephalo-pathy and CONUT score were independent factors influencing the incidence of OHE of Budd-Chiari syndrome patients who underwent TIPSS ( odds ratio=8.36, 1.74, 95% confidence interval as 1.02?68.75, 1.12?2.69, P<0.05). (3) Prediction of OHE after TIPSS. Results of ROC curve showed that the AUC of the CONUT score, the Child-Pugh score of liver function and the integrated model of end-stage liver disease (iMELD) score in predicting the incidence of OHE after TIPSS was 0.77(95% confidence interval as 0.64?0.91, P<0.05), 0.71(95% confidence interval as 0.56?0.87, P<0.05) and 0.71(95% confidence interval as 0.53?0.88, P<0.05), respectively, and there was no significant difference between the AUC of the CONUT score and the Child-Pugh score of liver function or the iMELD score ( Z=0.84, 0.59, P>0.05). The optimal cutoff value of CONUT score in predicting the incidence of OHE after TIPSS was 7, with the sensitivity, specificity and Yodon index as 78.6%, 61.8% and 0.40, respectively. Conclusion:The CONUT score can be used to predict the incidence of OHE in Budd-Chiari syndrome patients who underwent TIPSS, and the discrimination of CONUT score is equivalent to the Child-Pugh score of liver function and the iMELD score.

Value of blood ammonia and cholinesterase in the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy / 临床肝胆病杂志

Objective To investigate the value of serum markers in the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE). Methods A prospective analysis was performed for 81 patients who were hospitalized and treated in General Hospital of Ningxia Medical University from April 2020 to February 2022, and all these patients were diagnosed with hepatitis B cirrhosis based on clinical manifestation, laboratory examination, and radiological examination or liver biopsy. According to digital connection test A (NCT-A) and digital symbol test (DST), these patients were divided into simple cirrhosis group with 45 patients and MHE group with 36 patients. Related indices were measured, including liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBil)], albumin, blood ammonia, cholinesterase, and prothrombin time. The independent samples t -test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The logistic regression analysis and the area under the ROC curve (AUC) were used to investigate the predictive factors for MHE. Results Compared with the simple cirrhosis group, the MHE group had a significant increase in NCT-A score ( Z =-7.110, P < 0.001) and a significant reduction in DST score ( t =12.223, P < 0.001). The univariate analysis showed that there were significant changes in AST, albumin, prothrombin time, cholinesterase, and blood ammonia in the patients with MHE ( Z =-2.319, -2.643, -1.982, -6.594, and -5.331, all P < 0.05), while the multivariate analysis showed that only cholinesterase and blood ammonia were significant predictive factors (all P < 0.05) and were correlated with Child-Pugh score (all P < 0.05). Cholinesterase, blood ammonia, and their combination had an AUC of 0.925, 0.845, and 0.941, respectively, in the diagnosis of MHE, with an optimal cut-off value of 2966, 60, and 0.513, respectively. Conclusion Blood ammonia, cholinesterase, and their combined measurement have a potential clinical value in the early diagnosis of liver cirrhosis with MHE.

Thoughts on the diagnosis and treatment of hepatic encephalopathy associated with blood ammonia in liver cirrhosis / 临床肝胆病杂志

Hepatic encephalopathy is a serious complication of liver cirrhosis and can cause neuropsychiatric symptoms such as cognitive impairment and motor impairment. More than 30% of patients with liver cirrhosis may develop hepatic encephalopathy， posing a huge economic burden to the health of patients and bringing many challenges to clinical diagnosis and treatment. Therefore， early identification， diagnosis， and treatment are the key to improving patient prognosis. Based on the clinical experience of our center， this article elaborates on hepatic encephalopathy from the aspects of pathogenesis， time dimension， minimal hepatic encephalopathy， and non-organic brain lesions， in order to provide new ideas or strategies for the diagnosis and treatment of hepatic encephalopathy in liver cirrhosis.

Therapeutic effect of retention enema with compound rhubarb decoction on a rat model of minimal hepatic encephalopathy based on bile acid metabolomics / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of rhubarb decoction （RD） retention enema on a rat model of minimal hepatic encephalopathy （MHE） and its mechanism of action based on bile acid （BA） metabolomics. MethodsA total of 55 male Sprague－Dawley rats were randomly divided into blank group （NC group with 10 rats）， hepatic encephalopathy group （HE group with 15 rats）， MHE group with 15 rats， and MHE+rhubarb decoction treatment group （MHEY group with 15 rats）. Intraperitoneal injection of carbon tetrachloride （CCl4） and thioacetamide （TAA） was performed to establish a rat model of MHE or HE， and the rats were sacrificed after 2 weeks of administration. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， total bilirubin （TBil）， and total bile acid （TBA） and the concentration of blood ammonia were measured； the colonic contents were collected to measure pH value； liver and brain tissue samples were collected， and HE staining was used to observe the histopathological changes of the liver； the bile was collected， and liquid chromatography－mass spectrometry was used to perform BA－targeted metabolomics analysis. Continuous data were expressed as mean±standard deviation； a one－way analysis of variance was used for comparison between multiple groups， and the least significant difference t－test was used for further comparison between two groups. ResultsCompared with the NC group， the HE group and the MHE group had a significant increase in searching platform latency （after modelling and after administration） and a significant reduction in the number of platform crossings （all P<0.05）； compared with the MHE group， the MHEY group had a significant reduction in searching platform latency （after administration） and a significant increase in the number of platform crossings， and the HE group had a significant increase in searching platform latency and a significant reduction in the number of platform crossings （all P<0.05）. Compared with the NC group， the HE group and the MHE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）； compared with the MHE group， the MHEY group had significant reductions in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）， and the HE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）. The MHE group had significantly lower TBA， primary BA， and secondary BA than the NC group （all P<0.05）； compared with the MHE group， the HE group had significantly lower TBA and primary BA （all P<0.05）， and the MHEY group had significantly higher TBA and primary BA （all P<0.05）. Compared with the NC group， the MHE group had significant reductions in GCDCA， GUDCA， GHDCA， TCDCA， TUDCA， GLCA， and TLCA （all P<0.05） and significant increases in γ－MCA， THCA， 7－KDCA， AlloLCA， and α－MCA （all P<0.05）， and compared with the MHE group， the MHEY group had significant increases in THDCA， TMCA， TCDCA， TUDCA， and TLCA （all P<0.05）. ConclusionRD retention enema can improve liver injury and cognitive function in a rat model of MHE induced by CCl4 and TAA by regulating the enterohepatic circulation of BA， possibly by increasing the synthesis of taurine－binding BA.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Effects of sarcopenia on the occurrence of overt hepatic encephalopathy in patients with liver cirrhosis / 中华消化杂志

Objective:To investigate the risk factors of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis, and to clarify the effect of sarcopenia on OHE.Methods:Based on the liver cirrhosis cohort established by our research group, from January 1, 2013 to December 31, 2017, 480 patients diagnosed with liver cirrhosis and underwent upper abdominal computed tomography were selected from 3 centers, including the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai East Hospital Affiliated to Tongji University, and Shandong Provincial Hospital. The L3 skeletal muscle index (L3-SMI) <44.77 cm 2/m 2 for males and L3-SMI <32.50 cm 2/m 2 for females were used as the diagnostic criterion for sarcopenia. The clinical data of all the patients were collected, including baseline medical history, age, serum total bilirubin, serum levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), albumin, sodium, prothrombin time (PT), international normalized ratio (INR), hemoglobin, platelet count, etc, as well as Child-Pugh classification of liver function, and model for end-stage liver disease (MELD) score. Independent sample t test, rank sum test, and chi-square test were used for statistical analysis. Binary logistic regression analysis was used to analyze the independent risk factors for OHE in patients with liver cirrhosis, and Kaplan-Meier method was used to analyze the effect of sarcopenia on the incidence of OHE in patients with liver cirrhosis. Results:After 2 years of follow-up, the incidence of OHE was 16.2% (78/480). The age, serum total bilirubin level, AST, GGT, PT, INR, Child-Pugh score, and MELD score of OHE patients were all higher than those of non-OHE patients ((59.67±10.30) years old vs. (53.41±12.06) years old, 35.25 μmol/L(20.10 μmol/L, 60.53 μmol/L) vs. 22.70 μmol/L(15.10 μmol/L, 35.20 μmol/L), 40.00 U/L(27.25 U/L, 61.00 U/L) vs. 33.00 U/L(24.75 U/L, 47.00 U/L), 52.50 U/L(26.25 U/L, 86.75 U/L) vs. 34.50 U/L(22.00 U/L, 73.00 U/L), (17.71±3.52) s vs. (15.50±2.98) s, 1.50±0.34 vs. 1.31±0.29, 8.95±2.19 vs.7.20±1.94, 13.56±4.42 vs.11.42±3.92), while serum albumin, serum sodium and platelet count of OHE patients were all lower than those of non-OHE patients ((29.72±5.55) g/L vs. (33.19±5.89) g/L, 139.00 mmol/L(136.00 mmol/L, 142.00 mmol/L)vs.140.00 mmol/L (138.00 mmol/L, 142.00 mmol/L), 60.00×10 9/L(43.75×10 9/L, 90.25×10 9/L) vs. 80.00×10 9/L(56.00×10 9/L, 131.00×10 9/L)), and the differences were statistically significant ( t=-4.77; Z=-4.10, -3.13, -2.24; t=-5.19, -4.71, -6.57, -3.98, 4.99; and Z=2.44 and 3.48; all P<0.05). The proportions of ascites, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis at baseline, and the incidence of sarcopenia in OHE patients were all higher than those in non-OHE patients (82.1%, 64/78 vs. 63.7%, 256/402; 41.0%, 32/78 vs. 3.5%, 14/402; 5.1%, 4/78 vs. 1.0%, 4/402; 14.1%, 11/78 vs. 2.5%, 10/402; 37.2%, 29/78 vs. 19.7%, 79/402), and the L3-SMI of OHE patients was lower than that of non-OHE patients ((43.14±8.97) cm 2/m 2 vs. (46.29±8.49) cm 2/m 2), and the differences were statistically significant ( χ2=9.11, 101.97, 4.52, 18.38, 10.53; t=2.86; all P<0.05). The results of binary logistic regression analysis indicated that platelet count ( OR=0.995, 95% confidence interval (95% CI) 0.991 to 1.000, P=0.038), L3-SMI ( OR=0.959, 95% CI 0.922 to 0.997, P=0.035) and hepatic encephalopathy ( OR=14.724, 95% CI 6.741 to 32.161, P<0.001) were independent influencing factors for OHE in patients with liver cirrhosis. The incidence of OHE in patients with sarcopenia was higher than that of patients without sarcopenia (26.9%, 29/108 vs. 13.2%, 49/372), and the difference was statistically significant ( χ2=10.53, P=0.001). The results of Kaplan-Meier analysis demonstrated that patients with sarcopenia were more likely to develop OHE ( P<0.001). Conclusion:Sarcopenia is closely correlated to OHE and is an independent predictor of OHE in patients with liver cirrhosis.

Utilidad del sistema de recirculación de adsorbentes moleculares en la falla hepática: "diálisis hepática" / Usefulness of the molecular adsorbent recirculating system in liver failure: "liver dialysis"

INTRODUCCIÓN. La falla hepática ya sea aguda o crónica reagudizada representa un reto para el clínico ya que sus complicaciones conllevan una gran mortalidad, esto se ve aún más complicado ya que las opciones terapéuticas son limitadas, incluso muchas veces no se puede acceder a un programa de trasplante hepático oportuno que mejore la sobrevida de estos pacientes, es así que se ha desarrollado un sistema de "diálisis" hepática conocido como sistema de recirculación de adsorbentes moleculares el cual hace un efecto de detoxificación para eliminar sustancias que generan una noxa en el cuerpo humano. OBJETIVO. Entender la utilidad del sistema recirculante molecular adsorbente en la falla hepática, conocer sus indicaciones y complicaciones. METODOLOGÍA. Se realizó una revisión de la literatura con un enfoque descriptivo, retrospectivo cualitativo no experimental, de documentos que tratan sobre la utilización del sistema MARS para tratar la falla hepática, con evidencia desde el año 2004 hasta el 2021. La revisión bibliográfica se llevó a cabo en bases de datos como Pubmed, Embase, BVS, Google Scholar y Elsevier. RESULTADOS. Se identificaron 30 artículos que cumplieron criterios de inclusión de un grupo original de 343 artículos revisados. Se ha determinado que la evidencia sobre este sistema está compuesta sobre todo por reportes de caso y son pocos los ensayos controlados aleatorizados que empleen su uso, sin embargo, se ha podido determinar que este sistema es un puente al trasplante renal mientras se estabiliza al paciente en la Unidad de Cuidados Intensivos, disminuye los marcadores de falla hepática. CONCLUSIÓN. En Latinoamérica su uso es casi nulo de ahí la necesidad de entender el mecanismo de este novedoso sistema.

INTRODUCTION. Hepatic failure, whether acute or chronic, represents a challenge for the clinician since its complications entail a great mortality, this is even more complicated since the therapeutic options are limited, even many times it is not possible to access a timely liver transplant program to improve the survival of these patients, Thus, a hepatic "dialysis" system known as molecular adsorbent recirculation system has been developed, which has a detoxification effect to eliminate substances that generate a noxa in the human body. OBJECTIVE. To understand the usefulness of the molecular adsorbent recirculating system in liver failure, to know its indications and complications. METHODOLOGY. A literature review was performed with a descriptive, retrospective qualitative non-experimental qualitative approach, of papers dealing with the use of the MARS system to treat liver failure, with evidence from 2004 to 2021. The literature review was conducted in databases such as Pubmed, Embase, BVS, Google Scholar and Elsevier. RESULTS. Thirty articles were identified that met inclusion criteria from an original group of 343 articles reviewed. It has been determined that the evidence on this system is mainly composed of case reports and there are few randomized controlled trials that employ its use, however, it has been determined that this system is a bridge to renal transplantation while the patient is stabilized in the Intensive Care Unit, decreasing the markers of liver failure. CONCLUSIONS. In Latin America its use is almost null, hence the need to understand the mechanism of this novel system.

Lista de espera para transplante hepático: impacto clínico e econômico / Waiting list for liver transplantation: clinical and economic burden

ABSTRACT Background Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). Objective: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. Methods The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. Results: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). Conclusion: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

RESUMO Contexto O impacto da doença é um indicador relacionado ao estado de saúde. Dados epidemiológicos norte-americanos e europeus mostraram que, nas últimas décadas, o impacto da doença hepática crônica tem aumentado significativamente. Não há estudos que avaliem o impacto das descompensações da doença hepática crônica na lista de espera para transplante hepático (TxH) com doador falecido. Objetivo: Determinar o impacto clínico e econômico das descompensações da doença hepática nos pacientes em lista de espera sob a perspectiva do centro transplantador. Métodos Foram analisados, retrospectivamente, os prontuários de 104 pacientes incluídos em lista de espera para TxH com doador falecido entre outubro de 2012 e maio de 2016 e acompanhados integralmente no centro transplantador. Dados clínicos foram obtidos do prontuário eletrônico, enquanto dados econômicos foram coletados através de software de gestão hospitalar. A apropriação dos custos médicos diretos foi realizada sob duas metodologias: custeio por absorção pleno e microcusteio. Resultados: A descompensação com maior incidência foi a ascite refratária (20,2%) seguida de encefalopatia portossistêmica (12,5%). A média de internações por paciente foi de 1,37±3,42. A hemorragia digestiva alta varicosa foi a descompensação com maior tempo mediano de internação (18 dias), seguida da síndrome hepatorrenal (13,5 dias). A descompensação mais onerosa foi a síndrome hepatorrenal (custo médio de US$ 3.565), seguida encefalopatia portossistêmica (US$ 2.576) e a hemorragia digestiva alta varicosa (US$ 1.530). Conclusão O impacto da doença hepática crônica inclui um custo importante para os sistemas de saúde. Além disso, é provável que seja ainda maior em decorrência do curso insidioso da doença.

Embolización de colaterales portosistémicas espontáneas como tratamiento de la encefalopatía hepática refractaria / Embolization of spontaneous portosystemic shunts as treatment for refractory hepatic encephalopathy

BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis associated with a reduced survival. The presence of high-flux spontaneous porto-systemic shunts can induce HE even in patients with preserved liver function. AIM: To evaluate the effect of spontaneous porto-systemic shunt embolization (SPSE) over HE and its long-term evolution. MATERIAL AND METHODS: Retrospective analysis of 11 patients (91% males) with severe HE non-responsive to medical treatment in whom a SPSE was performed. The grade of HE (employing West Haven score), survival, MELD and Child-Pugh score, ammonia levels, degree of disability (employing the modified Rankin scale (mRs)) were evaluated before and at thirty days after procedure. RESULTS: The most common etiology found was non-alcoholic steatohepatitis (63.6%). A reduction of at least two score points of HE was observed in all patients after thirty days. There was a significant reduction on median (IQR) West Haven score from 3 (2-3) at baseline to 1 (0-1) after the procedure (p < 0.01). Twelve months survival was 63.6%. There was a decrease in median ammonia level from 106.5 (79-165) (ug/dL) to 56 (43-61) after SPSE (p = 0.006). The median mRS score before and after the procedure was 3 (3-5) and 1 (1-2.5), respectively (p < 0.01). Conclusions: According to our experience, SPSE is a feasible and effective alternative to improve HE and functionality of patients with refractory EH.

Diagnosis and Management of Pediatric Acute Liver Failure: ESPGHAN and NASPGHAN 2022

Guidelines for management of pediatric acute liver failure (PALF) were recently published by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). We, herein, update the readers about the diagnosis and management of PALF with emphasis on the changes in assessment and staging of hepatic encephalopathy, administration and goals of supportive therapy, frequency of monitoring, and management of complications.

Advances in the application of Stroop test in minimal hepatic encephalopathy / 临床肝胆病杂志

Minimal hepatic encephalopathy(MHE) is an early stage of hepatic encephalopathy with an insidious onset and a high rate of missed diagnosis in clinical practice, and it is of great importance to diagnose MHE as early as possible and provide effective clinical intervention. There are many diagnostic methods for MHE, among which psychometric hepatic encephalopathy score is the most commonly used method at present, but its wide application in clinical practice is limited by its complex and time-consuming operation, and therefore, it is urgent to find a simple, rapid, and effective clinical diagnostic method. Stroop test is a test for psychomotor speed and cognitive flexibility, and its value in the diagnosis of MHE has been verified in various countries including the United States and South Korea. This article introduces the development of Stroop test and its application in MHE, and the analysis shows that Stroop test based on mobile devices has a high sensitivity in the diagnosis of MHE and is simple, convenient, and feasible. It is hoped that this test can be widely used in the clinical work of MHE screening in China in the future.

Covert hepatic encephalopathy in liver cirrhosis: Risk factors and prognosis / 临床肝胆病杂志

Objective To investigate the risk factors for covert hepatic encephalopathy (CHE) in patients with liver cirrhosis and their influence on prognosis. Methods A total of 416 patients with liver cirrhosis who were hospitalized in a grade A tertiary hospital in Chongqing from September 2019 to June 2020 were enrolled in the study, and according to the presence or absence of CHE, they were divided into CHE group with 212 patients and non-CHE group with 204 patients. Clinical data and laboratory examination results were collected, and follow-up was performed for 6 months. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test, the continuous correction chi-square test, and the Mann-Whitney U test were used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to analyze the risk factors for CHE. Results The incidence rate of CHE was 51%. The univariate analysis showed that age, course of disease, the medical history of hepatic encephalopathy (HE), infection, ascites, electrolyte disturbance, hepatorenal syndrome, Child-Pugh class, prothrombin time, total bilirubin, creatinine, platelet, prothrombin activity, albumin, and Model for End-stage Liver Disease (MELD) score were the influencing factors for CHE (all P < 0.05). The multivariate logistic regression analysis showed that the medical history of HE ( OR =10.848, 95% CI : 4.971-23.674, P < 0.05), transjugular intrahepatic portosystemic shunt (TIPS) ( OR =4.334, 95% CI : 1.203-15.621, P < 0.05), Child-Pugh class ( OR =4.968, 95% CI : 1.299-18.992, P < 0.05), and MELD score ( OR =1.253, 95% CI : 1.161-1.352, P < 0.05) were independent predictive factors for CHE ( P < 0.05). The follow-up study showed that CHE had an effect on the short-or medium-term readmission, HE, and death of patients (all P < 0.05). Conclusion CHE has a relatively high incidence rate and greatly affects the prognosis of patients with liver cirrhosis. The development of CHE should be taken seriously in patients with a past history of HE, a history of TIPS, Child-Pugh class C liver function, and a high MELD score, and identification, screening, and intervention should be performed as early as possible to improve the prognosis of patients with liver cirrhosis.

Effect of underdilated stent on the occurrence of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt creation / 中华内科杂志

Objective:To evaluate whether underdilated stent could reduce the occurrence of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation.Methods:A total of 197 patients with decompensated liver cirrhosis, who had underwent TIPS creation at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively, including 110 males and 87 females with age 25-79 (54±11) years old. Uncovered and covered stents with 8 mm diameter were implanted in all subjects, and then dilated by balloon catheters with 6 mm or 8 mm diameter. The patients were divided into two groups, including underdilated group (6 mm, n=105) and control group (8 mm, n=92).Kaplan-Meier curves were used to illustrate cumulative rate of HE, and the differences were assessed with the log-rank test. Multivariate analyses with a Cox regression model were conducted to explore the risk factors for HE. Results:During a median follow-up period of 29 (12-54) months, 16 (15.2%) patients developed HE in the underdilated group and 27 (29.3%) patients in the control group. There was a significant difference in the cumulative rate of HE ( P=0.014), but no statistical differences were found in terms of variceal rebleeding, shunt dysfunction and survival between the two groups ( P=0.608, P=0.659, P=0.968). In multivariated analysis, group assignment (underdilated vs. control, HR=0.291, 95% CI 0.125-0.674, P=0.004) was identified as an independent risk factor for HE after TIPS creation. Conclusion:Underdilated TIPS could reduced the risk of HE compared with completely dilated TIPS, with comparable risk of variceal rebleeding, shunt dysfunction and mortality. And it is worthy of applying this technique to a large sample of patients in clinical practice.

A prospective multicenter and real-world study on the diagnostic value of combination of number connection test-B and line tracing test in mild hepatic encephalopathy / 中华消化杂志

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

An excerpt of 2022 European Association for the Study of the Liver clinical practice guidelines on the management of hepatic encephalopathy / 中华消化杂志

In 2022, the European Association for the Study of the Liver clinical practice guideline on the management of hepatic encephalopathy (HE) present evidence-based answers to a set of relevant questions, which formulated in participant, intervention, comparison and outcome (PICO) format on the definition, diagnosis, differential diagnosis and treatment of HE. The document does not cover the pathophysiology of HE and does not cover all available treatment options. We present the readers with translations and summarizations of the above mentioned recommendations. The methods through which it was developed and any information relevant to its interpretation are also provided.