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.

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.

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.

Uso do Stroop EncephalApp para o screening de encefalopatia hepática mínima em pacientes cirróticos no sul do Brasil / Use of the stroop encephalapp for covert hepatic encephalopathy screening in cirrhotic patients in southern brazil

ABSTRACT BACKGROUND: Covert hepatic encephalopathy (CHE) is difficult to detect due to the lack of easily applicable screening tools. The Stroop EncephalApp is a smartphone application already validated for CHE screening. However, its applicability to the Brazilian population is not known. OBJECTIVE: To estimate the prevalence of CHE and evaluate the use of Stroop EncephalApp in a cirrhotic population in Brazil. METHODS: In this cross-sectional study, we evaluated 99 patients previously diagnosed with liver cirrhosis in a Private Hospital in Curitiba/PR. Patients were initially submitted to the mini mental state examination (MMSE) to exclude individuals with dementia. After, the Psychometric Hepatic Encephalopathy Score (PHES) test was performed and lastly, the Stroop EncephalApp test. Results were adjusted for age, sex and education levels to evaluate the accuracy of the app on detecting the disease, comparing its results with the gold standard method (PHES). Patients with one or more of the following were excluded: dementia, inadequate MMSE score, illiteracy, color blindness, history of drugs/alcohol abuse within the past 3 months and previous or actual episodes of encephalopathy. The statistical analysis was performed by SPSS 2.0 and the significance adopted by 5%. RESULTS: We included 82 individuals in the final analysis. Among these patients, 29 were diagnosed with CHE by the PHES test (35.36% prevalence) and 28 of those obtained equal diagnosis by the Stroop EncephalApp (96.6% sensitivity). A total of 53 patients obtained negative results for CHE by PHES, while the Stroop test classified 27 of them as having the disease. In the multivariate analysis, high levels of education were associated with better performance during the tests. No significant relationship was observed between age and sex with the probability of diagnosing CHE through the PHES test.

RESUMO CONTEXTO: A encefalopatia hepática mínima (EHM) é uma complicação neuro-psiquiátrica da cirrose cuja detecção é dificultada pela falta de ferramentas práticas. O Stroop EncephalApp é um aplicativo de smartphones capaz de detectar a doença, entretanto sua aplicabilidade na população brasileira ainda não é conhecida. OBJETIVO: Avaliar o uso do Stroop EncephalApp para diagnóstico e avaliação de EHM em uma população de pacientes cirróticos no Brasil. MÉTODOS: Através de um estudo observacional transversal, 99 indivíduos sabidamente cirróticos foram recrutados do ambulatório de hepatologia de um hospital privado em Curitiba/PR. Primeiramente, foram aplicados o mini exame do estado mental (MEEM) para excluir indivíduos com demência; após, foram aplicados o Escore Psicométrico da Encefalopatia Hepática (PHES), atual padrão-ouro para diagnóstico de EHM, e posteriormente o Stroop EncephalApp, ajustando para idade, sexo e anos de formação acadêmica, buscando avaliar a eficiência do aplicativo em detectar a doença e comparar seus resultados com o atual padrão-ouro. Foram excluídos do estudo indivíduos com demência, pontuação insuficiente no MEEM, analfabetos, daltônicos, e com histórico de abuso de álcool/drogas ilícitas nos últimos 3 meses e paciente com episódios prévios ou atuais de encefalopatia hepática. A análise estatística foi realizada pelo SPSS 2.0 e a significância adotada em 5%. RESULTADOS: Um total de 82 indivíduos foram incluídos na análise final. Destes, 29 foram diagnosticados com EHM (35,36% de prevalência) através do PHES e 28 obtiveram o mesmo resultado após a aplicação do Stroop (96,6% de sensibilidade). Cinquenta e três pacientes obtiveram um resultado negativo para EHM através do PHES, sendo que 27 desses obtiveram um resultado positivo para EHM através do Stroop. Na análise multivariada, níveis elevados de escolaridade estiveram associados com melhor desempenho durante a execução dos testes. Não houve associação significativa entre idade e sexo com a probabilidade de apresentar encefalopatia através do PHES. CONCLUSÃO: O Stroop EncephalApp é uma ferramenta viável e com boa sensibilidade para o screening de EHM, mas possui baixa especificidade na população estudada.

Algunos aspectos clínicos y humorales de la insuficiencia hepática en niños y adolescentes / Some clinical and humoral aspects of liver failure in children and adolescents

Introducción: La insuficiencia hepática aguda es una entidad de origen multifactorial, que se presenta en niños previamente sanos y tiene repercusión directa en las funciones de síntesis, coagulación y depuración. Objetivo: Caracterizar niños con insuficiencia hepática aguda según variables clínicas y humorales. Métodos: Se realizó un estudio retrospectivo y descriptivo de 19 pacientes con el diagnóstico de insuficiencia hepática aguda, atendidos en la Unidad de Cuidados Intensivos Pediátricos del Hospital Docente Infantil Sur de Santiago de Cuba, desde abril de 1998 hasta igual mes de 2018, para lo cual se emplearon métodos teóricos y estadísticos. Resultados: En la casuística predominó el sexo femenino (57,9 %), la mediana de la edad fue de 5 años y la infección constituyó la causa más común (73,7 %). Los virus hepatotrópicos como el de la hepatitis A resultaron los más frecuentes. Las complicaciones de mayor observancia fueron la alcalosis respiratoria (63,1 %), la disfunción multiorgánica (42,1 %) y la encefalopatía hepática (31,6 %). Las cifras bajas de colesterol y el tiempo de protrombina mayor de 20 segundos se asociaron a una mayor letalidad. Conclusiones: En los pacientes menores de un año los virus no hepatotrópicos constituyeron el origen más frecuente de dicha enfermedad.

Introduction: The acute liver failure is an entity of multifactorial origin that is presented in previously healthy children and has direct repercussion in the synthesis, clotting and purification functions. Objective: To characterize children with acute liver failure according to clinical and humoral variables. Methods: A retrospective and descriptive study of 19 patients with diagnosis of acute liver failure was carried out, they were assisted in the Pediatric Intensive Cares Unit of the Southern Children Hospital in Santiago de Cuba, from April, 1998 to the same month in 2018, for which theoretical and statistical methods were used. Results: In the case material there was a prevalence of the female sex (57.9 %), the mean age was 5 years and the infection constituted the most common cause (73.7 %). The hepatotropic virus as the hepatitis A were the most frequent. The complications of more observance were the respiratory alkalosis (63.1 %), the multiorganic dysfunction (42.1 %) and the liver brain disease (31.6 %). The low figures of cholesterol and the prothrombin time higher than 20 seconds were associated with a greater lethality. Conclusions: In the patients younger than one year the non hepatotropic virus constituted the most frequent origin in this disease.

A fatal case of multi-organ failure in acute yellow phosphorus poisoning

Phosphorus is a nonmetallic irritant used in various sectors like rodenticide, firecracker industries, match industries, and fertilizers. Phosphorus poisoning is responsible for deaths among children and adults. Accidental yellow phosphorus poisoning is frequently reported in children, whereas suicidal consumption is not uncommon amongst adults. Herein, we present the case of a 30-year-old female patient who ingested Ratol paste containing yellow phosphorus in an attempt to commit suicide. Her initial chief complaints were nausea, vomiting along with loose motion during hospitalization, followed by a symptomless phase with stable vitals on the 2nd day, and managed conservatively. She took discharge against the medical advice. Later on, she was readmitted in the same hospital, after two days, complaining of generalized weakness, bodily pain, drowsiness, loss of appetite, and breathing difficulties. She developed severe complications due to the intoxication and died. An autopsy was performed. The histopathological and the toxicological examination were carried out. We found characteristic features in different organs due to yellow phosphorus toxicity. We concluded the cause of death as hepatic encephalopathy and multi-organ dysfunction syndrome caused by the yellow phosphorus poisoning.

El impacto del tratamiento de la encefalopatía hepática mínima en el pronóstico a largo plazo / The impact of minimal hepatic encephalopathy treatment in long-term prognosis

La encefalopatía hepática mínima (EHm) afecta del 30% al 50% de los pacientes cirróticos. Su detección es esencial por su relación con la encefalopatía hepática clínica, la alteración de la habilidad para conducir, el mayor riesgo de caídas, la alteración de la calidad de vida, la progresión más acelerada de la cirrosis y la supervivencia. A pesar de la información fidedigna de su relevancia clínica, pronóstica y social, la detección de EHm no está generalizada en la práctica clínica. El espectro de la encefalopatía hepática engloba diversas alteraciones de las funciones cerebrales, por lo que se requiere realizar más de un test para su diagnóstico. Además, las alteraciones iniciales difieren de un paciente a otro. Esto ha dificultado el desarrollo de una estrategia diagnóstica universal. Como resultado, no disponemos de datos suficientes para generar recomendaciones basadas en la evidencia del impacto del tratamiento de la EHm en la calidad de vida y la supervivencia, así como de su rentabilidad. Por lo tanto, las guías clínicas actuales sugieren que se evalúe la EHm cuando se afecta la calidad de vida de los pacientes, ya que no se conocen las consecuencias del tamizaje. Las terapias reductoras de amonio se consideran la piedra angular del tratamiento de la EHm. Los disacáridos no absorbibles, la rifaximina y, más recientemente, los probióticos, han mostrado efectos beneficiosos. Se necesitan más ensayos controlados con placebo para evaluar la eficacia, seguridad y rentabilidad de los regímenes de tratamiento disponibles para evaluar el impacto del tratamiento de la EHm en el pronóstico a largo plazo de estos pacientes.

Minimal hepatic encephalopathy (MHE) affects up to 30-50% of cirrhotic patients. The detection of MHE is essential because of its relationship with overt hepatic encephalopathy, impairment of motor vehicle driving abilities, higher risk of falls, quality of life impairment, faster cirrhosis progression and survival. Despite the robust evidence regarding its clinical, prognostic and social relevance, MHE testing is not widespread in routine clinical care. Hepatic encephalopathy spectrum covers various alterations in complex brain functions, requiring more than one test to be quantified. In addition, initial disturbances differ from one patient to another. All this has made it difficult to develop a universal diagnostic strategy. As a consequence, there is a lack of available robust data in the literature to generate evidence-based recommendations related to the impact of MHE treatment on quality of life and survival of these patients, as well as on cost-effectiveness. Therefore, current clinical guidelines suggest MHE testing only when patients have problems with their quality of life, since consequences of the screening procedure are still unclear. Ammonia lowering therapies have been considered the cornerstone of MHE treatment. Beneficial effects of non-absorbable disaccharides (lactulose or lactitol), rifaximin and more recently, probiotics have been reported. Further placebo-controlled trials are needed to assess the efficacy, safety, and cost-effectiveness of available treatment regimes to evaluate the impact of MHE treatment on the long-term prognosis of these patients.

Encefalopatia hepática secundária à intoxicação por Tephrosia cinerea em ovinos / Hepatic encephalopathy secondary to poisoning by Tephrosia cinerea in sheep

A intoxicação por Tephrosia cinerea causa fibrose hepática periacinar em ovinos na região semiárida do Nordeste, com quadro clínico de ascite acentuada, e, ocasionalmente, com sinais neurológicos. Neste trabalho foram estudadas 16 ovinos em 6 surtos de intoxicação por T. cinerea. Todos os ovinos apresentaram lesões histológicas de fibrose periacinar e seis apresentaram, no encéfalo, vacuolização da substância branca e da junção entre a substância branca e a cinzenta com presença de astrócitos de Alzheimer tipo II na substância cinzenta. A doença foi reproduzida experimentalmente em dois ovinos que apresentaram ascite, desvios vasculares (shunts) porto-sistêmicos e sinais nervosos com lesões histológicas semelhantes a dos casos espontâneos. Na técnica de imuno-histoquímica houve marcação fraca ou ausente do citoplasma astrocitário para o anticorpo anti-GFAP em seis ovinos evidenciando uma alteração degenerativa, em que os astrócitos acumulam corpos densos e reduzem o volume de GFAP. Houve marcação positiva para o anticorpo anti-S100 em oito ovinos, incluindo os dois ovinos experimentais o que sugere reatividade celular, com proliferação mitocondrial e de retículo endoplasmático liso. Estas alterações são caraterísticas dos efeitos da amônia nos astrócitos. Conclui-se que na intoxicação por T. cinerea em alguns ovinos ocorrem sinais nervosos em consequência da encefalopatia hepática.(AU)

In the semiarid region of northeastern Brazil, Tephrosia cinerea causes periacinar hepatic fibrosis in sheep with severe ascites and, occasionally, nervous signs. Sixteen sheep from six outbreaks of T. cinerea poisoning were studied. All sheep had histologic lesion of periacinar fibrosis and six showed, in the brain, vacuolization (spongy degeneration) of the white matter and junction between grey and white matter and presence of Alzheimer type II astrocytes in the grey matter. The disease was produced experimentally in two sheep, that presented porto-sistemic shunts and similar histologic lesions as those observed in the spontaneous cases. Immunohistochemistry revealed weak labelling with anti-GFAP antibodies suggesting a degenerative alteration of astrocytes with accumulation of dense bodies and reduction of the GFAP. There was strong labelling with anti-S100 antibodies suggesting cellular reactivity with proliferation of mitochondria and endoplasmatic reticulum. Such alterations are characteristic of the effects caused by ammonia on the astrocytes. It is concluded that in poisoning by T. cinerea nervous signs due to hepatic encephalopathy occur in some sheep.(AU)

Consecuencias del amonio en la fatiga central en atletas, posible efecto neuroprotector del ejercicio / Ammonium consequences in athletes' central fatigue and its possible neuroprotection effect thanks to physical activity / Consequências do amônio na fadiga central em atletas, possível efeito neuroprotetor do exercício

Introducción. La fatiga central en el deporte está asociada a los efectos del amonio. La principal fuente de producción de amonio durante el ejercicio es el músculo esquelético. El amonio se genera como consecuencia del metabolismo energético, debido a la oxidación de aminoácidos y a la desaminación del nucleótido de adenosin trifosfato. Objetivo. Presentar una reflexión sobre el efecto del amonio durante el ejercicio de alta intensidad y su relación con la fatiga central en atletas. Discusión. Durante el ejercicio, la concentración de amonio alcanza valores superiores a 200µM (micromolar); sin embargo, en un adulto promedio se considera que valores superiores a 60µM en sangre manifiestan un trastorno por hiperamonemia. El amonio influye en la disminución del rendimiento en atletas y está asociado con los efectos nocivos para la salud en pacientes con encefalopatía hepática. Conclusiones. La práctica del ejercicio físico genera neuroprotección contra las altas concentraciones de amonio en el cerebro, pues, durante el ejercicio con altas concentraciones de amonio, los atletas no presentan los síntomas de pacientes con encefalopatía hepática, lo que implica adaptaciones metabólicas que juegan un papel importante en el metabolismo del amonio en el cerebro. [Porras-Álvarez J. Consecuencias del amonio en la fatiga central en atletas, posible efecto neuroprotector del ejercicio. MedUNAB. 2018;21(1): 115-121 doi: 10.29375/01237047.3394].

Introduction. Central fatigue in sports training is associated with ammonium effects within the human body. The ammonium main production source during physical training is located in skeletal muscles and it is generated as a result of energy metabolism. This process is caused by amino acids oxidation and adenosine triphosphate nucleotide deamination. Objective. This article's objective is to present an analysis regarding ammonium effects when high intensity sports are performed and its relation with central fatigue in athletes. Discussion. When high intensity sport practices are performed, ammonium concentration levels can reach values higher than 200 µM (micromolar). However, it is considered that an average adult with ammonium levels higher than 60µM evidences a hyperammonemia disorder. Ammonium has direct influence in the decline of athletic performance and it is associated with harmful effects for hepatic encephalopathy patients. Conclusions. Physical activity practice creates neuroprotection against high-quantities of ammonium in the brain. Although in physical practices athletes have high amounts of ammonium, they do not show symptoms related to hepatic encephalopathy; thus, this situation implies that metabolic adaptations have an important role within ammonium metabolism in the brain. [Porras-Álvarez J. Ammonium consequences in athletes' central fatigue and its possible neuroprotection effect thanks to physical activity. MedUNAB. 2018;21(1):115-121doi: 10.29375/01237047.3394].

Introdução. A fadiga central no esporte está associada aos efeitos do amônio. A fonte de produção do amônio mais importante durante o exercício é o músculo esquelético. O amônio é gerado como consequência do metabolismo energético, devido à oxidação dos aminoácidos e à desaminação do trifosfato de adenosina. Objetivo. Apresentar uma reflexão sobre o efeito do amônio durante o exercício de alta intensidade e sua relação com a fadiga central em atletas. Discussão. Durante o exercício, a concentração do amônio atinge valores superiores a 200µM (micromol); no entanto, em um adulto médio, considera-se que valores superiores a 60µM no sangue mostram um distúrbio por hiperamonemia. O amônio influencia a diminuição do desempenho em atletas e está associado a efeitos nocivos para a saúde em pacientes com encefalopatia hepática. Conclusões. A prática de exercício físico gera neuroproteção contra altas concentrações do amônio no cérebro, pois, durante o exercício com altas concentrações do amônio, os atletas não apresentam sintomas de encefalopatia hepática, o que implica adaptações metabólicas que desempenham um papel importante no metabolismo do amônio no cérebro. [Porras-Álvarez J. Consequências do amônio na fadiga central em atletas, possível efeito neuroprotetor do exercício. MedUNAB. 2018;21(1):115-121doi: 10.29375/01237047.3394].

Central pontine myelinolysis after liver transplantation: case report / Mielinolisis Póntica Central post-trasplante hepático: Reporte de Caso

SUMMARY Central Pontine Myelinolysis (CPM) is a demyelinating disease with central pontine localization which presents in patients with chronic hepatic disease and hydroelectrolytic disturbances. In spite of pathophysiology still unknown, the patient liver transplanted has several risk factors to CPM. Its clinical manifestations are mainly motor and awareness alterations. Diagnosis requires brain images like magnetic resonance and it has a poor prognosis in critical care patients and it is very important to know about the possibility of presentation and to be aware about this pathology. The main objective to present this case report is sensitizing the medical community regarding the CPM in patients with liver transplant. The case report of a 40-year-old female patient who had previous history of biliary cirrhosis secondary to autoimmune hepatitis and liver transplantation was performed; subsequently developed alteration of awareness, hydroelectrolytic disturbances and abnormal findings in brain imaging. CPM is a neurological demyelinating disease with multifactorial origin, its treatment is supportive and prevention is the main goal in patients with risk factors like patient after liver transplantation.

RESUMEN La Mielinólisis Pontica Central es una enfermedad desmielinizante con localización pontina central que se presenta especialmente en pacientes con enfermedad hepática crónica y alteraciones hidroelectrolíticas. A pesar de la fisiopatología aún desconocida, el paciente con trasplante hepático tiene varios factores de riesgo para su desarrollo. Sus manifestaciones clínicas son principalmente alteraciones motoras y de conciencia. El diagnóstico requiere imágenes cerebrales como la resonancia magnética y se asocia a mal pronóstico. En los pacientes de cuidados críticos y es muy importante conocer la posibilidad de presentación y tener conciencia de esta patología. El objetivo principal de este reporte de caso es sensibilizar a la comunidad médica respecto en pacientes posterior a trasplante hepático. Se realizó el reporte de una paciente de 40 años de edad con antecedente de cirrosis biliar secundaria a hepatitis autoinmune y trasplante de hígado; posteriormente desarrolló alteración de la conciencia, alteraciones hidroelectrolíticas y hallazgos anormales en la imagen cerebral. La Mielinolísis Póntica es una enfermedad desmielinizante neurológica de origen multifactorial, su tratamiento es de apoyo y la prevención es el objetivo principal en pacientes con factores de riesgo como el paciente tras trasplante hepático.

Cerebral hemodynamic and metabolic changes in fulminant hepatic failure / Modificações da hemodinâmica e metabolismo cerebral na insuficiência hepatica fulminante

ABSTRACT Intracranial hypertension and brain swelling are a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure (FHF). The pathogenesis of these complications has been investigated in man, in experimental models and in isolated cell systems. Currently, the mechanism underlying cerebral edema and intracranial hypertension in the presence of FHF is multi-factorial in etiology and only partially understood. The aim of this paper is to review the pathophysiology of cerebral hemodynamic and metabolism changes in FHF in order to improve understanding of intracranial dynamics complication in FHF.

RESUMO O edema cerebral e a hipertensão intracraniana (HIC) são as principais causas de morbidade e mortalidade de pacientes com insuficiência hepática fulminante (IHF). A patogênese dessas complicações tem sido investigada no homem, em modelos experimentais e em sistemas celulares isolados. Atualmente, o mecanismo subjacente ao edema cerebral e HIC na presença de IHF é multifatorial em etiologia e pouco compreendido na literatura. O objetivo deste trabalho é revisar a fisiopatologia das alterações hemodinâmicas e metabólicas cerebrais na IHF, visando melhorar a compreensão da complicação da hemodinâmica encefálica na IHF.

Observational Cohort Study of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Abstract: Introduction and aim. Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. Material and methods. A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher’s exact test, χ2, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. Results. 257 (37.9%) patients developed HE after TIPS. Patients’ age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. Conclusion. We have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?

Abstract: Introduction. Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn’t. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Neuron-derived CCL2 contributes to microglia activation and neurological decline in hepatic encephalopathy

BACKGROUND: CCL2 was up-regulated in neurons and involved in microglia activation and neurological decline in mice suffering from hepatic encephalopathy (HE). However, no data exist concerning the effect of neuron-derived CCL2 on microglia activation in vitro. METHODS: The rats were pretreated with CCL2 receptor inhibitors (INCB or C021, 1 mg/kg/day i.p.) for 3 days prior to thioacetamide (TAA) administration (300 mg/kg/day i.p.) for inducing HE model. At 8 h following the last injection (and every 4 h after), the grade of encephalopathy was assessed. Blood and whole brains were collected at coma for measuring CCL2 and Iba1 expression. In vitro, primary neurons were stimulated with TNF-α, and then the medium were collected for addition to microglia cultures with or without INCB or C021 pretreatment. The effect of the medium on microglia proliferation and activation was evaluated after 24 h. RESULTS: CCL2 expression and microglia activation were elevated in the cerebral cortex of rats received TAA alone. CCL2 receptors inhibition improved neurological score and reduced cortical microglia activation. In vitro, TNF-α treatment induced CCL2 release by neurons. Medium from TNF-α stimulated neurons caused microglia proliferation and M1 markers expression, including iNOS, COX2, IL-6 and IL-1ß, which could be suppressed by INCB or C021 pretreatment. The medium could also facilitate p65 nuclear translocation and IκBα phosphorylation, and NF-κB inhibition reduced the increased IL-6 and IL-1ß expression induced by the medium. CONCLUSION: Neuron-derived CCL2 contributed to microglia activation and neurological decline in HE. Blocking CCL2 or inhibiting microglia excessive activation may be potential strategies for HE.

Eficacia y seguridad de rifaximina alfa en pacientes con encefalopatia hepatica refractaria al uso de lactulosa / Efficacy and safety of rifaximin alfa in patients with hepatic encephalopathy refractory to the use of lactulose

INTRODUCCIÓN: Antecedentes: El presente dictamen responde a la solicitud de evaluación del uso del petitorio de Rifaximina alfa en pacientes con encefalopatia hepática refractaria al uso de lactulosa. Aspectos Generales: Se estima que aproximadamente 5.5 millones de personas en los Estados Unidos sufren de cirrosis hepática, una causa de movilidad y mortalidad tanto en este país como en el mundo. La encefalopatia hepática o encefalopatía portosistemica constituye una complicación de la cirrosis hepática y falla de la función neuropsiquiátrica asociada con falla en la función hepática. A pesar que la condición es frecuentemente diagnosticada aún no existe un claro entendimiento de la patogénesis. Sin embargo, se estipula que se puede deber a un incremiento en las concentraciones de amoniaco en vista que el higado ya no es capaz de eliminar las toxinas de la sangre causando así toxicidad en el cerebro. Puede presentarse como episodios agudos o crónicamente a largo plazo. Tecnología Sanitaria de Interés: La Rifaximina alfa es un agente antimicrobiano con un amplio espectro de acción sobre Bacterias Gram-positivas y Gram- negativas, tanto aerobias como anaerobais. La característica de Rifaximina alfa es su forma polimorfa alfa y su escasa absorción en el tracto gastrointestinal (inferior a 1%), lo cual favorece la concentración del fármaco en el intestino y sobre todo, en las heces en forma activa. METODOLOGÍA: Estrategia de Búsqueda: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de Rifaximina alfa para el tratamiento de pacientes con encefalopatía hepática con resistencia (falla) al tratamiento estándar con lactulosa. La búsqueda se inicio revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras com la Food and Drug Administration (FDA), la European Medicines Agency (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriomente se buscaron Guías de Práctica Clínica a través de los metabuscadores: Translating Research into Practice (TRIPDATABASE), National Library of Medicine (Pubmed-Medline), The National Guuideline of Clearinghouse, y Health Systems Evidence. Finalmente. se realizó una búsqueda dentro de la información generada por grupos internacionales que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica. RESULTADOS: Sinopsis de la Evidencia: En la presente sinopsis se describe la evidencia disponible que sustenta la eficacia y seguridad de Rifaximina alfa para el tratamiento de pacientes con encefalopatia hgepática refractarios al tratamiento estándar con lactulosa. CONCLUSIONES: A la fecha, no se ha evaluado la eficacia y seguridad de Rifazimina alfa como monoterapia ni en pacientes refractarios a lactulosa, por lo que la evidencia encontrada responde la pregunta PICO de manera indirecta. Actualmente no existe alternativa de tratamiento a lactulosa en el Petitorio Farmacológico de EsSalud, por lo que es necesario contar con una alternativa de tratamiento para así evitar el deterioro de la calidad de vida del paciente, dadas las limitaciones en las funciones cognitiva y psicomotriz a la que la enfermedad conlleva. El Instituto de Evaluacioón de Tecnologías en Salud e Investigación-IETSI, aprueba el uso de Rifaximina alfa en pacientes con encefalopatía hepática refractaria al uso de lactulosa. El presente Dicatamen Preliminar tiene una vigencia de dos años a partir de su fecha de publicación.

Tablas de normalidad de la población en Cuba para las pruebas psicométricas utilizadas en el diagnóstico de la encefalopatía hepática mínima / Cuban Normality Tables for Psychometric Tests Used for Diagnosis of Minimal Hepatic Encephalopathy

Objetivos: la encefalopatía hepática mínima constituye el estadio subclínico previo al desarrollo de encefalopatía hepática clínica en el paciente cirrótico, además de asociarse con un deterioro de la calidad de vida de estos pacientes y con un riesgo incrementado de accidentes laborales e incapacidad de conducción de vehículos. El Psychometric Hepatic Encephalopathy Score es considerado actualmente el método diagnóstico de elección en el diagnóstico de la EHM. El objetivo de este trabajo fue diseñar las tablas de normalidad del PHES para la población cubana. Población y métodos: se estudió una muestra conformada por 520 personas sanas de las provincias de Villa Clara, Sancti Spíritus y Cienfuegos. Las mismas realizaron las 5 pruebas incluidas en el PHES. Se analizaron las variables edad, sexo, años de escolarización, procedencia y consumo diario de alcohol. Mediante la prueba de la t de Student, ANOVA y el coeficiente de correlación de Pearson, se realizó el análisis univariante. Se efectuó un análisis de regresión lineal múltiple para cada prueba, y se construyeron las tablas de normalidad. Resultados: en el análisis multivariante (regresión lineal múltiple) la edad y los años de escolarización fueron las 2 variables independientes relacionadas con el rendimiento en cada una de las cinco pruebas. Conclusión: la disponibilidad de las tablas de normalidad del PHES permitirá contar con un método diagnóstico de referencia aplicable a los pacientes cubanos con cirrosis hepática, sin la necesidad de configurar grupos controlados por la edad y el nivel de escolaridad regionalmente

Objectives: Minimal hepatic encephalopathy (MHE) is the subclinical stage prior to the development of clinical hepatic encephalopathy in cirrhotic patients. For these patients, it is associated with impaired quality of life, increased risk of accidents, and incapacity for driving vehicles. The Psychometric Hepatic Encephalopathy Score (PHES) is currently considered to be the diagnostic method of choice for diagnosis of MHE. The aim of this work was to design PHES normality tables for the Cuban population. Population and Methods: The study sample consisted of 520 healthy people from the provinces of Villa Clara, Sancti Spiritus and Cienfuegos who all took the 5 tests included in the PHES. Variables of age, sex, years of schooling, place of origin, and daily alcohol consumption were analyzed. Univariate analysis with the Student’s t test, ANOVA and Pearson correlation coefficient was performed. Multivariable linear regression for each test was performed and normality tables were constructed. Results: Multivariate analysis used multiple linear regression with age and years of schooling as the independent variables related to performance for each of the 5 tests. Conclusions: The availability of normality tables provides a diagnostic reference method for PHES which is applicable to Cuban patients with liver cirrhosis without requiring control groups for age and regional education level

Falla hepática aguda sobre crónica / Acute-On-Chronic Liver Failure

La falla hepática aguda sobre crónica (ACLF, del inglés Acuteon Chronic Liver Failure) comprende el deterioro agudo de la función hepática en un paciente que tiene de base una enfermedad hepática crónica de novo o conocida y desencadenada por diferentes factores precipitantes que pueden ser hepáticos o extrahepáticos. Dentro de las manifestaciones clínicas se encuentran: disfunción renal, encefalopatía hepática y falla orgánica multisistémica, que de no ser tratadas oportunamente se traducen en mal pronóstico. Se han utilizado varias puntuaciones para valorar la función hepática y el pronóstico de los pacientes. A pesar de que la falla orgánica multisistémica es una contraindicación para el trasplante hepático, este sigue siendo la mejor opción de tratamiento para estos pacientes

Acute-on-chronic liver failure (ACLF) includes acute deterioration of liver functions in patients with either chronic de novo liver disease or already diagnosed liver disease. ACLF can be triggered by various hepatic or extrahepatic precipitating factors. Among its clinical manifestations are renal dysfunction, hepatic encephalopathy, and multisystem organ failure. If not treated promptly translate the prognosis can be poor. Several scoring systems have been used to assess liver function and patient prognosis. Although multisystem organ failure contraindicates liver transplantation, it remains the treatment of choice for this patients

Encefalopatía hepática mínima / Minimal Hepatic Encephalopathy

La encefalopatía hepática mínima (EHM) es un síndrome neurocognitivo, potencialmente reversible, constituido por una serie de alteraciones neuropsicológicas en pacientes con hepatopatía aguda o crónica, sin evidencia de anormalidades neurológicas durante la exploración física. La EHM es responsable del déficit cognitivo y tiene un impacto negativo sobre la calidad de vida de los pacientes, esencialmente con diagnóstico de cirrosis. La imposibilidad para detectar de manera clínica las alteraciones neuropsicológicas, alienta al clínico para la utilización de pruebas psicométricas, las cuales constituyen la base del cribado y el diagnóstico. La EHM modifica el pronóstico de la enfermedad. La detección oportuna permite intervenir el riesgo de desarrollar encefalopatía hepática clínica (EH) en los pacientes con cirrosis, lo cual se ha relacionado con una menor supervivencia.

Minimal hepatic encephalopathy (MHE) is a potentially reversible neurocognitive syndrome that consists of a series of neuropsychological disorders in patients with acute and chronic liver disease. A physical examination may or may not show evidence of neurological abnormalities. MHE is responsible for cognitive impairment, has a negative impact on quality of life of patients, essentially cirrhosis. The impossibility of detecting this neuropsychological disorder clinically has led to the use of psychometric tests for screening and diagnosis. MHE modifies the prognosis of disease, and early detection allows intervention against the risk of developing clinical hepatic encephalopathy (HE) in patients with cirrhosis which has been associated with decreased survival.

Tablas de normalidad de la población en Cuba para los test psicométricos utilizados en el diagnóstico de la encefalopatía hepática mínima / Normality tables of the population in Cuba for the psychometric tests used in the diagnosis of minimal hepatic encephalopathy

Objetivo: la encefalopatía hepática mínima constituye el estadio subclínico previo al desarrollo de encefalopatía hepática clínica en el paciente cirrótico, además de asociarse a un deterioro de la calidad de vida de estos pacientes y a un riesgo incrementado de accidentes laborales e incapacidad de conducción de vehículos. El Psychometric Hepatic Encephalopathy Score es considerado actualmente el método diagnóstico de elección en el diagnóstico de la EHM. El objetivo de este trabajo fue diseñar las tablas de normalidad del PHES para la población cubana. Métodos: se estudió una muestra conformada por 520 personas sanas de las provincias de Villa Clara, Sancti Spíritus y Cienfuegos. Las mismas realizaron los cinco tests incluidos en el PHES. Se analizaron las variables edad, sexo, años de escolarización, procedencia, y consumo diario de alcohol. Mediante la prueba de la t de Student, ANOVA y el coeficiente de correlación de Pearson se realizó el análisis univariante. Se efectuó un análisis de regresión lineal múltiple para cada test y se construyeron las tablas de normalidad. Resultados: en el análisis multivariante (regresión lineal múltiple) la edad y los años de escolarización fueron las dos variables independientes relacionadas con el rendimiento en cada uno de los cinco test. Conclusiones: la disponibilidad de las tablas de normalidad del PHES permitirá contar con un método diagnóstico de referencia aplicable a los pacientes con cirrosis hepática cubanos, sin la necesidad de configurar grupos controlados por edad y nivel de escolaridad regionalmente.

Objective: minimal hepatic encephalopathy (MHE) is the subclinical stage pre-clinical development of hepatic encephalopathy in cirrhotic patients, in addition to associated with impaired quality of life of these patients and an increased risk of accidents and disability of driving. The Psychometric Hepatic Encephalopathy Score (PHES) is currently considered the diagnostic method of choice in the diagnosis of MHE. The objective of this work was to design tables PHES normality for the Cuban population. Method: a sample composed of 520 healthy people in the provinces of Villa Clara, Sancti Spiritus and Cienfuegos were studied. They made the five tests included in the PHES. The variables age, sex, years of education, origin, and daily alcohol consumption were analyzed. By t test of Student, ANOVA and Pearson correlation coefficient univariate analysis. an analysis of multiple linear regression for each test was performed and normal tables were constructed. Results: in the multivariate analysis (multiple linear regression) age and years of schooling were the two independent variables related to performance in each of the five tests. Conclusions: the availability of tables PHES normality will provide a diagnostic method applicable reference to patients with liver cirrhosis Cubans, without the need to configure controlled for age and education level regional groups.