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.

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.

Therapeutic effects of blood purification in treatment of fulminant hepatic failure

OBJECTIVES: To evaluate the clinical effects of blood purification for treating fulminant hepatic failure (FHF). METHODS: Thirty-three severe FHF patients with hepatic encephalopathy (HE) above grade III were subjected to a combined blood purification treatment in addition to the comprehensive liver protection therapy. Patients underwent continuous hemofiltration on a daily basis during the daytime followed by sequential treatment with plasma exchange or hemodialysis every 2-3 days. The therapeutic effects of this treatment were evaluated. RESULTS: After treatment with blood purification, restoration of consciousness (those who abandoned the treatment without restoration of consciousness were excluded) was achieved in 6 of 8 cases (75%) in acute liver failure (ALF) group, 3 of 3 cases (100%) in subacute liver failure (SALF) group, and 9 of 14 cases (64.29%) in acute/subacute on chronic liver failure (A/SCLF) group. Of all cases, 11 patients restored consciousness after 7 days in a coma. The rate of long-term survival (those who abandoned the treatment were excluded) was 3/7 (42.86%) for ALF group, 2/2 (100%) for SALF group, and 1/11 (9.09%) for A/SCLF group. The levels of hemoglobin and platelet in peripheral blood were significantly reduced after blood purification. CONCLUSIONS: Treatment of FHF patients with daily continuous hemofiltration during the daytime is effective in treating HE and in improving health status in the early stages of the disease. Long-term prognosis also benefits from this treatment. The rate of consciousness recovery and long-term survival is highest in SALF group followed by ALF group. This treatment is less effective in A/SCLF patients. It should be noted that blood purification procedure may cause damage to blood cells.

Encefalopatía hepática mínima: conceptos actuales sobre una entidad emergente / Minimal hepatic encephalopathy: current concepts of an emerging clinical entity

Hepatic encephalopathy (HE) is a reversible neuropsychiatric disorder, consequence of hepatocellular failure and/or portal shunt to the systemic circulation. The neurological abnormalities are heterogeneous, affecting different cognitive and motor functions and its magnitude has a wide spectrum, ranging from a subclinical level (minimal hepatic encephalopathy, MHE) to coma. The relevance of MHE has been recognized only recently, with studies that have shown high prevalence among cirrhotic patients and significant complications such as poor quality of life, risk of vehicular accidents, predisposition to development overt HE and increased mortality. Despite this, one of the limitations for routine screening is the lack of a simple and objective diagnostic method, since MHE is not detectable by conventional medical assessment and diagnosis is only made through specialized tests that assess different cognitive domains. There isn´t a diagnostic gold standard; and some of the most recognizable methods that have been implemented in clinical practice in some countries are: Psychometric Hepatic Encephalopathy Score, Critical Flicker Frequency, and Inhibitory Control Test. The main therapies that have been evaluated for EHM are lactulose and rifaximin, with favorable impact on different outcomes. More multicentric studies with longer follow-up and clinically relevant outcomes that demonstrate the cost-effectiveness of screening and treatment of this important complication are needed.

La encefalopatía hepática (EH) corresponde a un trastorno neuropsiquiátrico reversible producido como consecuencia de una falla hepatocelular y/o de la desviación del flujo portal a la circulación sistémica.El compromiso producido es heterogéneo, afectando diversas funciones cognitivas y motoras y su magnitud presenta un amplio espectro que abarca desde un nivel subclínico correspondiente a la encefalopatíahepática mínima (EHM), hasta el coma. La relevancia de la EHM se ha reconocido sólo recientemente, conestudios que han mostrado su alta prevalencia entre los pacientes cirróticos y una trascendencia clínicasignificativa, asociándose a una pobre calidad de vida, riesgos de accidentalidad vial, predisposición a desarrollo de EH evidente y mayor mortalidad. A pesar de lo anterior, una de las limitantes para su pesquisarutinaria es la falta de un método diagnóstico simple y objetivo, ya que la EHM no es detectable medianteuna evaluación médica convencional y sólo se diagnostica a través de test especializados que evalúan distintosdominios cognitivos. No existe un estándar de oro diagnóstico; entre los métodos más reconocidos y que se han implementado en la práctica clínica enalgunos países se encuentran el Score Psicométrico de Encefalopatía Hepática, el Test de Frecuencia Críticade Parpadeo, y el Test de Control Inhibitorio. Entre las terapias para EHM más evaluadas se encuentran la lactulosa y rifaximina, con impacto favorable en distintos outcomes, sin embargo, faltan estudios multicéntricos, con seguimientos prolongados y con objetivos clínicamente relevantes que demuestren la costo-efectividad de la pesquisa y tratamiento de estarelevante complicación.

Encefalopatía hepática en el 2011 / Hepatic encephalopaty in 2011

Hepatic encephalopathy (HE) is a neuropsychiatric and motor disorder, resulting from hepatic failure. It is one of the main manifestations of chronic liver disease and the cardinal presentation of acute liver failure. Its presence and severity are the main prognostic determinants among these patients. It is frequent in advanced chronic liver disease (30-45 percent) and in patients with TIPS (transjugular intrahepatic portosystemic shunt) (10-50 percent). Its pathogenesis is complex and it has multiple components, including ammonia, inflammatory cytokines, benzodiazepine- and manganese-like components, which alter the function of the neuronal cell. Its management requires identification and treatment of the precipitating factors, and ruling out other causes of mental status alteration. The majority of the therapies are aimed at reducing ammonia load in the intestine, such as non absorbable disaccharides (lactulose), antibiotics (neomycin, metronidazole and currently, rifaximin) and other, whose role has yet to be established. Severe encephalopathy is considered an indicator for liver transplantation. This article will analyze mainly hepatic encephalopathy in cirrhotic patients, its classification, etiopathogeny and current management.

La encefalopatía hepática (EH) es un síndrome neuropsiquiátrico y motor, que resulta de una disfunción hepática. Es una de las manifestaciones principales de la enfermedad hepática crónica y la presentación cardinal en la falla hepática aguda. Su presencia y gravedad son uno de los mayores determinantes pronósticos en estos pacientes. Es frecuente en enfermedad hepática crónica avanzada (30-45 por ciento)y en portadores de shunt postosistémico transyugular intrahepático (TIPS) (10-50 por ciento). Su patogénesis es compleja y tiene múltiples componentes, incluyendo el amonio, citoquinas inflamatorias, compuestos que semejan a benzodiacepinas y manganeso, que causan alteración funcional de la célula neuronal. El manejo requiere identificar y tratar los factores precipitantes, además de excluir otras causas de alteración del estado mental. La mayoría de las terapias están dirigidas a reducir la carga de amonio en el intestino, tales como los disacáridos no absorbibles (lactulosa), antibióticos (neomicina, metronidazol y actualmente rifaximina) y otros cuyo rol está por establecerse. La encefalopatía grave es considerada un indicador para trasplante hepático. En este artículo analizaremos principalmente la encefalopatía hepática en pacientes con cirrosis, su clasificación, etiopatogenia y manejo actual.

Eficacia de la terapia combinada lactulosa/l-ornitinal-aspartato vs. lactulosa en encefalopatía hepáticahiperamonémica: estudio retrospectivo en el hospital “Luis Vernaza”, Guayaquil, Ecuador. Enero 2006 a diciembre 2010 / Efficacy of lactulosa/l-ornitina- l-aspartate combined therapy vs. lactulose in hyperammonemic hepatic encephalopathy: a retrospective study at “Luis Vernaza” hospital, Guayaquil, Ecuador. From january 2006 to december 2010

Objetivo: determinar la efectividad de la terapia combinada lactulosa/l-ornitina l-aspartato (L/LOLA) vs lactulosa (L) en relación a la mejoría clínica de acuerdo a la escala West Haven y reducción de amonio en los pacientes con encefalopatía hepática durante 7 días. Metodología: estudio retrospectivo de expedientes clínicos de los pacientes ingresados desde enero 2006 a diciembre 2010 con diagnóstico de encefalopatía hepática en el hospital “Luis Vernaza”. Resultados: se revisaron 301 registros médicos de los cuales 78 fueron elegidos para el estudio (L=31, L/LOLA=47) evidenciándose predominio en grados de encefalopatía II con 38.5% (n=30) y III con 51.3% (n=40) de la población total estudiada. Se observó que el 80.65% (n=25) de los pacientes con lactulosa mejoraron su estadío de encefalopatía vs el 65.96% (n=31) del grupo con terapia combinada (p=0.16). En relación al amonio se encontró una disminución de 84.19mcg/dL en el grupo con lactulosa vs 80.83 mcg/dL con la terapia combinada (p=0.45). Se encontró que el 66.6% (n=52) del total de pacientes en estudio tuvieron MELD (Model for End-Stage Liver Disease) > 16. Finalmente el 78.2% (n=61) de la población del estudio cursó con trombocitopenia. Conclusiones: la terapia combinada no demostró resultados significativos comparados con lactulosa al evaluar mejoría clínica y reducción de niveles de amonio a los 7 días. Se debe realizar estudios prospectivos usando LOLA con mayor duración de terapia y evaluar terapias complementarias.

Objective: to determine the effectiveness of the lactulose/l-ornithine l-aspartate (L/LOLA) combined therapy vs. lactulose (L) in relation to clinical improvement according to the West Haven scale and the reduction of ammonia in patients with hepatic encephalopathy during 7 days. Methodology: retrospective study of the medical records of patients admitted to the “Luis Vernaza” hospital with a diagnosis of hepatic encephalopathy from January 2006 to December 2010. Results: 301 medical records were reviewed of which 78 were chosen for the study (L=31, L/LOLA=47) showing a prevalence of grade-II encephalopathy of 38.5% (n=30), and grade-III encephalopathy of 51.3% (n=40) of the total study population. It was observed that 80.65% (n=25) of the patients with lactulose improved their stage of encephalopathy vs. 65.96% (n=31) of the combined-therapy group (p=0.16). With respect to the ammonium, there was a decrease of 84.19 mcg/dL in the lactulose group vs. 80.83 mcg/dL in the combined therapy group (p=0.45). We found that 66.6% (n=52) of all the study patients had MELD (Model for End-Stage Liver Disease) > 16. Finally, 78.2% (n=61) of the study patients showed thrombocytopenia. Conclusions: the combined therapy did not show significant results compared with only lactulose when assessing clinical improvement and the reduction of ammonia levels after 7 days. Prospective studies should be done using LOLA with a longer duration of therapy; complementary therapies should also be evaluated.

Encefalopatia hepática / Hepatic encephalopathy

A encefalopatia hepática (EH) é um distúrbio funcional do sistema nervoso central (SNC) as»sociado à insuficiência hepática, de fisiopatolo»gia multifatorial e complexa. A EH associada àcirrose é atualmente classificada em episódica, persistente ou mínima. Seu diagnóstico deve ser baseado no achado de sinais e sintomas de cir»rose hepática e na exclusão de doenças do SNC. As medidas terapêuticas atualmente empregadas para o manejo da EH incluem identificação e re»moção dos fatores precipitantes, orientação nu»tricional, agentes farmacológicos e medidas pro»filáticas visando a prevenção de novos episódios de EH. Avaliação de elegibilidade para transplan»te de fígado deve ser considerada. As principais drogas usualmente empregadas para o tratamen»to da EH são os dissacarídeos não absorvíveis e antibióticos. Novas intervenções terapêuticas pro»missoras recentemente avaliadas para o tratamen»to de EH incluem a administração de L-ornitina»L-aspartato e, em casos selecionados, o uso de diálise extracorpórea de albumina (MARS) e oclu»são de shunts por radiologia intervencionista.

Probióticos: perspectivas médicas / Probiotics: medical perspectives

Este artigo revisa o tema probióticos com o objetivo de avaliar seus possíveis potenciais como agentes bioterapêuticos na prevenção e/ou tratamento de algumas doenças relacionadas com a via intestinal. Os probióticos representam uma área de pesquisa em extensão. Muitas publicações enfatizam o potencial significado dessa emergente área, entretanto muito ainda necessita ser comprovado e realizado no sentido de definir o real significado do termo probiótico; se for efetivo, quais as cepas que preenchem os critérios de um real microorganismo probiótico e em quais circunstâncias clínicas são indicadas

This article reviews the theme probiotics with the objective to evaluate their potentials as possible biotherapeutic agents for the prevention and/or treatment of some illnesses related tothe intestinal tract. Probiotics represents an expanding research area. Many publications emphasizes the potential significance of this emerging field, meanwhile, much still remains to be proved and to be done in order to standardize the real meaning of the term probiotic and, if they are real, which strains actually fulfill the criteria of true probiotics microorganisms and in which clinical circumstances they are really useful

Avaliação dos fatores precipitantes de encefalopatia hepática em pacientes com cirrose / Factors precipitating hepatic encephalopathy in patients with cirrhosis

Objetivo: A maioria dos episódios de Encefalopatia Hepática (EH) em pacientes com doença hepática crônica possui algum evento clínico precipitante reconhecido. A proposta deste estudo foi determinar as manifestações clínicas e os fatores desencadeantes de EH em pacientes com cirrose. Métodos: Cirróticos admitidos na emergência do Hospital de Clínicas de Porto Alegre por episódio de EH (n=20) foram avaliados quanto à presença de fatores precipitantes tais como infecção (incluindo peritonite bacteriana), hemorragia gastrointestinal, constipação, dieta rica em proteína, azotemia, hipocalemia, uso de drogas psicoativas, desidratação, desenvolvimento de hepatoma e outros. Todos os pacientes foram acompanhados até alta hospitalar ou óbito. Resultados: Todos os pacientes tiveram pelo menos um fator desencadeante de EH. O principal fator contribuinte para o desenvolvimento de EH foi infecção (60 por cento), como infecção urinária (35 por cento), infecção respiratória (20 por cento) e Peritonite Bacteriana Espontânea (15 por cento). Conclusão: A medida terapêutica mais importante na EH é identificar os fatores precipitantes e corrigi-los prontamente. O estudo mostra que estes eventos são muito comuns e o diagnóstico precoce de infecção é importante nestes casos

Peritoneal transplantation of human fetal hepatocytes for the treatment of acute fatty liver of pregnancy: a case report.

We report the case of a 26-year-old second gravida in the third trimester of pregnancy who presented with a history of nausea, repeated vomiting and jaundice. The patient was diagnosed as acute fatty liver of pregnancy. After delivery, the condition of the patient progressed to grade IV encephalopathy and did not improve despite all intensive clinical management measures. After 3 days in grade IV encephalopathy, the patient was infused 3 x 10(8) human foetal hepatocytes. The patient's level of consciousness started improving after 24 hours of foetal hepatocyte transfusion and she recovered completely within 7 days.

Complicações agudas das doenças hepáticas crônicas / Acute complications of chronic liver diseases

As doenças hepáticas crônicas, em fases avançadas, cursam com graves complicações, responsáveis pela maioria das indicações de internações hospitalares e causas de morte dos pacientes. Neste capítulo, são discutidas as principais complicações das doenças hepáticas crônicas, que são a encefalopatia hepática, a peritonite bacteriana espontânea e a síndrome hepatorrenal. São apresentados os aspectos importantes, na prática médica, dessas três condições clínicas, com ênfase na abordagem diagnóstica e terapêutica

Uso del flumazenil en encefalopatía hepática: reporte de un caso / Use of the flumazenil in hepática encefalopatía: report of a case

Paciente de sexo masculino, 53 años, internado por dos ocasiones en el Hospital de Portoviejo; presenta encefalopatía hepática producida por cirrosis alcohólica. Durante su primera estadía hospitalaria de 14 días, ingresó con GLASGOW 11/15; dentro del esquema terapéutico se utiliza el Flumazenil en dosis de 0.5 Mg IV a dosis respuesta, mejorando su estado neurológico con la primera dosis, se realiza paracentesis y continúa con medicación por vía oral, es dado de alta con régimen ambulatorio. Ingresa por segunda ocasión a la Unidad de Cuidados Intensivos (UCI), con ascitis, ictericia, anasarca, trastornos de la conciencia con GLASGOW 8/15; es tratado con una terapéutica que incluye al flumazenil, mejorando el paciente su estado neurológico...