MicroRNA-378 inhibits hepatocyte apoptosis during acute liver failure by targeting caspase-9 in mice.

BACKGROUND: Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. It has been demonstrated that micro ribonucleic acids (miRNAs) are crucial mediators of nearly all pathological processes, including liver disease. OBJECTIVE: The present study investigates the role of miR-378 in ALF. An ALF mouse model was induced using intraperitoneal injections of d-galactosamine/lipopolysaccharide (d-GalN/LPS). A hepatocyte cell line and miR-378 analogue were used in vitro to investigate the possible roles of miR-378 in ALF. METHODS: The expressions of miR-378 and predicted target genes were measured via reverse transcription-quantitative polymerase chain reaction and western blotting, and cell apoptosis was assayed using flow cytometry. RESULTS: Compared with mice in the control group, the mice challenged with d-GalN/LPS showed higher levels of alanine aminotransferase, aspartate aminotransferase, tumour necrosis factor-alpha and interleukin-6, more severe liver damage and increased numbers of apoptotic hepatocytes. Hepatic miR-378 was distinctly downregulated, while messenger RNA and protein levels of cysteinyl aspartate specific proteinase 9 (caspase-9) were upregulated in the ALF model. Furthermore, miR-378 was downregulated in d-GalN/TNF-induced hepatocyte cells, and miR-378 was found to inhibit hepatocyte apoptosis by targeting caspase-9. CONCLUSION: Together, the present results indicate that miR-378 is a previously unrecognised post-ALF hepatocyte apoptosis regulator and may be a potential therapeutic target in the context of ALF.

Guía Práctica ESPEN: nutrición clínica en las enfermedades del hígado / ESPEN Practical Guideline: clinical nutrition in liver disease

Introducción: la Guía Práctica se basa en la actual guía científica de la ESPEN sobre nutrición clínica en las enfermedades hepáticas. Métodos: se ha reducido y transformado en diagramas de flujo para facilitar su uso en la práctica clínica. La guía está dedicada a todos los profesionales, incluidos médicos, dietistas, Nutriciónistas y enfermeras, que trabajan con pacientes con enfermedad hepática crónica. Resultados: la guía presenta un total de 103 pronunciamientos y recomendaciones con breves comentarios para el manejo Nutricional y metabólico de pacientes con (i) insuficiencia hepática aguda grave, (ii) esteatohepatitis alcohólica, (iii) enfermedad hepática grasa no alcohólica, (iv) cirrosis hepática, y (v) cirugía o trasplante de hígado. Conclusión: las recomendaciones relacionadas con enfermedades están precedidas por recomendaciones generales sobre el diagnóstico del estado Nutricional en los pacientes hepáticos y sobre las complicaciones hepáticas asociadas a la nutrición médica (AU)

Background: the Practical Guideline is based on the current scientific ESPEN guide on Clinical Nutrition in Liver Disease Methods: it has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. Results: a total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. Disease-related recommendations are preceded by general recommendations on the diagnosis of nutritional status in liver patients and on liver complications associated with medical nutrition. Conclusion: this Practical Guideline gives guidance to health care providers involved in the management of liver disease on how to offer optimal nutritional care (AU)

[ESPEN Practical Guideline: clinical nutrition in liver disease]. / Guía Práctica ESPEN: nutrición clínica en las enfermedades del hígado.

Introduction: Background: the Practical Guideline is based on the current scientific ESPEN guide on Clinical Nutrition in Liver Disease. Methods: it has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. Results: a total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. Disease-related recommendations are preceded by general recommendations on the diagnosis of nutritional status in liver patients and on liver complications associated with medical nutrition. Conclusion: this Practical Guideline gives guidance to health care providers involved in the management of liver disease on how to offer optimal nutritional care.

Introducción: Introducción: la Guía Práctica se basa en la actual guía científica de la ESPEN sobre nutrición clínica en las enfermedades hepáticas. Métodos: se ha reducido y transformado en diagramas de flujo para facilitar su uso en la práctica clínica. La guía está dedicada a todos los profesionales, incluidos médicos, dietistas, nutricionistas y enfermeras, que trabajan con pacientes con enfermedad hepática crónica. Resultados: la guía presenta un total de 103 pronunciamientos y recomendaciones con breves comentarios para el manejo nutricional y metabólico de pacientes con (i) insuficiencia hepática aguda grave, (ii) esteatohepatitis alcohólica, (iii) enfermedad hepática grasa no alcohólica, (iv) cirrosis hepática, y (v) cirugía o trasplante de hígado. Conclusión: las recomendaciones relacionadas con enfermedades están precedidas por recomendaciones generales sobre el diagnóstico del estado nutricional en los pacientes hepáticos y sobre las complicaciones hepáticas asociadas a la nutrición médica.

Infecciones bacterianas no espontáneas en pacientes cirróticos hospitalizados, Hospital Central de las Fuerzas Armadas, marzo 2018-diciembre 2020

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Abstract: Introduction: Bacterial infections in cirrhotic patients are a frequent complication, which occurs mainly in advanced stages of the disease. Non-spontaneous infections or infections not related to portal hypertension include mainly those of the urinary tract, acute pneumonia, and skin and soft tissue infections. They generate a significant impact on the evolution of the disease, since they increase morbidity and mortality, and are also the most common precipitating factor of acute over chronic liver failure, a serious condition with high short-term mortality. The objective of this work is to know the incidence, and describe the clinical, epidemiological, microbiological, and evolutionary characteristics of non-spontaneous bacterial infections, in patients with liver cirrhosis, admitted to the Military Hospital, in the period between March 2018 and December 2020. Methodology: A cross-sectional, descriptive and single-center study was carried out, which included hospitalized patients, diagnosed with liver cirrhosis, who presented a bacterial infection not related to portal hypertension on admission or during hospital stay. Data were analyzed using frequency distribution and summary measures for the different variables. The incidence of non-spontaneous bacterial infections was calculated based on the total population of cirrhotic patients admitted during that period. Results: Of the total number of cirrhotic patients admitted, 17.5% had a bacterial infection not linked to portal hypertension, with a mean age of 61 years, 70% being men. The main etiology of cirrhosis was alcoholic. The vast majority of patients (95%) presented an advanced stage of liver disease (60% Child-Pugh stage B and 35% stage C), with a mean MELD-Na of 21. The most frequent infection was that of the urinary tract (50%), followed by acute pneumonia (20%), skin and soft tissue infections (10%) and acute cholangitis (10%). The most prevalent microorganisms were gram negative bacilli such as Klebsiella pneumoniae and Escherichia coli. 40% of the patients presented acute-on-chronic liver failure at the time of admission and an additional 5% developed it during evolution. Of this group of patients, 20% died during hospitalization. Conclusions: The present study constitutes an approximation to the knowledge of non-spontaneous infections in cirrhotic patients, being necessary the development of studies with a greater number of patients in order to establish a statistically significant association between the presence of bacterial infection and the development of acute on chronic liver failure, and from this with short-term mortality.

Resumo: Introdução: Infecções bacterianas em pacientes cirróticos são uma complicação frequente, que ocorre principalmente em estágios avançados da doença. Infecções não espontâneas ou infecções não relacionadas à hipertensão portal incluem principalmente aquelas do trato urinário, pneumonia aguda e infecções de pele e tecidos moles. Geram um impacto significativo na evolução da doença, pois aumentam a morbidade e a mortalidade, sendo também o fator precipitante mais comum da insuficiência hepática aguda sobre a crônica, uma condição grave com alta mortalidade em curto prazo. O objetivo deste trabalho é conhecer a incidência e descrever as características clínicas, epidemiológicas, microbiológicas e evolutivas das infecções bacterianas não espontâneas, em pacientes com cirrose hepática, internados no Hospital Militar, no período entre Março de 2018 e dezembro de 2020. Metodologia: Foi realizado um estudo transversal, descritivo e unicêntrico, que incluiu pacientes internados, com diagnóstico de cirrose hepática, que apresentavam infecção bacteriana não vinculada à hipertensão portal na admissão ou durante a internação. Os dados foram analisados ​​por meio de distribuição de frequência e medidas de resumo para as diferentes variáveis. A incidência de infecções bacterianas não espontâneas foi calculada com base na população total de pacientes cirróticos admitidos nesse período. Do total de cirróticos admitidos, 17,5% apresentavam infecção bacteriana não ligada à hipertensão portal, com média de idade de 61 anos, sendo 70% homens. A principal etiologia da cirrose foi alcoólica. A grande maioria dos pacientes (95%) apresentava doença hepática em estágio avançado (60% Child-Pugh estágio B e 35% estágio C), com média de MELD-Na de 21. A infecção mais frequente foi a do trato urinário (50%), seguida de pneumonia aguda (20%), infecções de pele e tecidos moles (10%) e colangite aguda (10%). Os microrganismos mais prevalentes foram bacilos gram negativos como Klebsiella pneumoniae e Escherichia coli. 40% dos pacientes apresentavam insuficiência hepática aguda-crônica no momento da admissão e outros 5% a desenvolveram durante a evolução. Desse grupo de pacientes, 20% morreram durante a internação. Conclusões: O presente estudo constitui uma aproximação ao conhecimento das infecções não espontâneas em pacientes cirróticos, sendo necessário o desenvolvimento de estudos com maior número de pacientes a fim de estabelecer uma associação estatisticamente significativa entre a presença de infecção bacteriana e o desenvolvimento de quadro agudo de insuficiência hepática crônica, e a partir disso com mortalidade a curto prazo.

Enfermedad de Wilson: experiencia de un centro de referencia en Colombia / Wilson's disease: Experience of a reference center in Colombia

Resumen Introducción: la enfermedad de Wilson es una enfermedad heterogénea causada por mutaciones en el gen ATP7B. La presentación clínica es variable, en fenotipos hepáticos y neuropsiquiátricos. El objetivo de este estudio es describir una cohorte retrospectiva de pacientes. Materiales y métodos: estudio retrospectivo descriptivo de pacientes atendidos en el Hospital Pablo Tobón Uribe desde enero de 2004 a septiembre de 2017. Resultados: se reportaron 27 pacientes, 17 hombres y 10 mujeres. El tiempo de seguimiento medio fue de 2,18 años, el 40% presentó síntomas neurológicos; el 29%, psiquiátricos; y el 85%, alteración hepática. En el laboratorio, el 85% presentó ceruloplasmina baja; 55%, cobre urinario alto; en casos con biopsia hepática, 7 tenían depósito de cobre en coloraciones especiales. En neuroimágenes, el 84% presentó hallazgos sugestivos de enfermedad de Wilson y en 3 casos se documentó una mutación genética patogénica. Durante el seguimiento, el 51% mejoró clínica o bioquímicamente, el 11% se mantuvo estable y el 18% se deterioró. El 88% de los casos sobrevivió al final del seguimiento. Conclusiones: este estudio es la cohorte retrospectiva más grande de Colombia. Los resultados son base para nuevos estudios poblacionales buscando de manera activa la enfermedad para documentarla en su fase preclínica y, de este modo, impactar en el pronóstico.

Abstract Introduction: Wilson's disease is a heterogeneous disorder caused by mutations in the ATP7B gene. Its clinical presentation is variable in hepatic and neuropsychiatric phenotypes. The aim of this study is to describe a retrospective cohort of patients. Materials and methods: A descriptive retrospective study was carried out in patients treated at the Hospital Pablo Tobón Uribe from January 2004 to September 2017. Results: 27 patients were reported, 17 men and 10 women. The mean follow-up time was 2.18 years. 40% of the patients had neurological symptoms, 29% psychiatric symptoms, and 85% hepatic impairment. Lab tests showed that 85% had low ceruloplasmin and 55% had increased urinary copper. In cases that underwent liver biopsy, 7 had special copper colorations. Neuroimaging revealed that 84% had findings suggestive of Wilson's disease and a pathogenic genetic mutation was documented in 3 cases. During follow-up, 51% improved clinically or biochemically, 11% remained stable, and 18% deteriorated. 88% of cases survived at the end of follow-up. Conclusions: This study is the largest retrospective cohort carried out in Colombia. The results are the basis for new population-based studies actively seeking this disease to describe its preclinical development and thus impact prognosis.

Mucosal expression of defensin-5, soluble phospholipase A2 and lysozyme in the intestine in a rat model of acute liver failure and its relationship to intestinal bacterial translocation.

INTRODUCTION: To study the expression of defensin-5 (RD-5), soluble phospholipase A2 (sPLA2) and lysozyme in the intestine in a rat model of acute liver failure and its relationship with intestinal bacterial translocation (BT). PATIENTS AND METHODS: Sprague-Dawley (SD) rats were divided into two groups. The experimental group was divided into five subgroups according to the lapsing time after the model was established, which were designated accordingly as 8h, 16h, 24h, 48h, and 72h groups. Acute liver failure (ALF) model was induced by intraperitoneal injection of 10% d-galactosamine. The homogenates of mesenteric lymph nodes (MLNs), liver and spleen from each group were cultured in agar to determine the bacterial outgrowth. The mRNA expression of RD-5, sPLA2, lysozyme and the protein expression of sPLA2, lysozyme were determined. RESULTS: No bacteria grew in the organ cultures from the control group while experimental groups had positive cultures. Expression of the RD-5 and sPLA2 mRNA in the experimental groups gradually increased at early time points and peaked 16h after induction of ALF, then progressively decreased. The mRNA expression of lysozyme in the experimental group peaked at 8h after ALF induction, then progressively decreased. Similar results were obtained with Western blot and immunohistochemical staining. DISCUSSION: The immune barrier function of the ileal mucosa in the rat model of acute liver failure was compromised as demonstrated by the decreased expression of RD-5, sPLA2 and lysozyme in Paneth cells along with increased intestinal bacterial translocation.

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.

Insuficiencia hepática fulminante por paracetamol / Fulminant hepatic failure due to paracetamol

Resumen: La insuficiencia hepática aguda es una enfermedad poco común pero que amenaza la vida y afecta con mayor frecuencia a pacientes que no tienen enfermedades preexistentes del hígado. El paracetamol (acetaminofén) es uno de los medicamentos analgésicos-antipiréticos prescritos con más frecuencia por los médicos y automedicados por las personas, cuyos efectos adversos son desde molestias leves hasta efectos adversos letales, que no necesariamente requieren la dosis tóxica para causar tales efectos graves. No es sorprendente que el paracetamol sigue siendo causa importante de sobredosis: desde intoxicaciones intencionadas (suicida) y no intencionadas (consumo crónico), cuyos efectos graves van desde la insuficiencia hepática fulminante relacionada con sobredosis hasta la muerte; la mitad de estos episodios se atribuyen al paracetamol y estos casos parecen estar aumentando cada vez más debido a su fácil acceso y venta libre. El objetivo de este artículo es comunicar un caso y revisar la bibliografía al respecto.

Abstract: Acute liver failure is a rare disease but life-threatening, and occurs more frequently in patients without preexisting liver disease. Paracetamol (acetaminophen) is one of the analgesic-antipyretic drugs most frequently prescribed by physicians and self- medicated by people, whose adverse effects are mild discomfort and even lethal side effects that do not necessarily require the toxic dose to cause such serious effects. Not surprisingly, acetaminophen remains a major cause of overdose: from intentional poisoning (suicide) and unintentional (chronic use), whose major effects are ranging from fulminant hepatic failure related to overdose to death; half of these episodes are attributable to paracetamol, and these cases seem to be increasing more and more, because of its easy access and free sale. The aim of this paper is to present a case report and a literature review.

Management of acute liver failure. Clinical guideline from the Catalan Society of Digestology. / Manejo de la insuficiencia hepática aguda grave. Documento de posicionamiento de la Societat Catalana de Digestologia.

Acute liver failure is an uncommon and severe disease characterised by a rapid onset of severe hepatocellular failure in individuals without previous liver disease. Initial management of this entity determines the outcome of the patient. Initial contact with the acute liver failure patients usually occurs in the emergency department, digestology clinic or, in more severe cases, intensive care units. The management of acute liver failure patients in all these cases must be multidisciplinary, involving surgeons and hepatologists who are experts in this condition, meaning those from hospitals with active liver transplant programmes. This article reviews the current body of evidence concerning the medical management of acute liver failure patients, from the suspected diagnosis and initial management to intensive medical treatment, including the need for an emergency liver transplantation. Moreover, we also review the use of artificial liver support systems in this setting.

Update on acute-on-chronic liver failure. / Actualización en la insuficiencia hepática aguda sobre crónica.

Acute-on-chronic liver failure (ACLF) is a recently defined syndrome characterised by acute decompensation of chronic liver disease, associated with organ failures and high mortality. ACLF is a common condition and may affect up to 30% of patients admitted to hospital for cirrhosis complications. Bacterial infections, alcoholism and reactivation of viral hepatitis are the most common precipitating factors in ACLF, although in up to 40% of patients no precipitating factor can be identified. Although the pathophysiology of ACLF is not completely understood, the presence of an excessive inflammatory response appears to play a key role. There is no specific treatment for patients with ACLF and management is based on organ support and liver transplantation. New treatment strategies based on liver support systems and immunomodulatory treatments are being evaluated but existing data are still limited.

Asociación de partición hepática y ligadura portal para hepatectomía por etapas (ALPPS) / Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)

La disfunción hepática postoperatoria del remanente hepático que ocurre en pacientes sometidos a grandes resecciones hepáticas, es un problema complejo y temido, dado su pronóstico incierto. La asociación de partición hepática y ligadura portal para hepatectomía por etapas (ALPPS), es un enfoque novedoso para pacientes portadores de enfermedad hepática oncológica que anteriormente eran considerados "no resecables". El procedimiento se realiza en dos etapas. La primera, comprende la ligadura de la rama derecha de la vena porta. Luego, se realiza la transección del parénquima hepático; incluyendo o no, la sección y ligadura de la vena hepática media. A continuación se empaqueta el hígado tumoral en una bolsa de polietileno y el abdomen es cerrado. La segunda etapa, se realiza 7 a 15 días después. Una vez abierto el abdomen, se retira la bolsa de polietileno; se ligan y seccionan la arteria, el conducto biliar y la vena hepática derechos; y se elimina el hígado tumoral. Pueden instalarse drenes y se procede al cierre de la laparotomía. La técnica ALPPS puede permitir entonces, la resección curativa de hígados tumorales en pacientes con lesiones considerados previamente como no resecables. El objetivo de este artículo fue describir las indicaciones y aspectos técnicos del ALPPS a propósito del primer caso realizado en nuestra ciudad, en una paciente de 47 años con un cáncer de vesícula biliar avanzado y metástasis bilobares.

Postoperative hepatic malfunction subsequent to insufficiency of hepatic remnant is a complex and dire problem in patients subjected to large hepatic resections. The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), is a novel approach for oncology patients whose hepatic tumors were previously considered non-resectable. The technique is performed in two phases. The first one comprises the ligation of the right portal vein branch. Subsequently, a parenchymal transection is performed, including or not, the middle hepatic vein. A plastic bag is employed to cover the tumoral liver, and the abdomen is closed. The second one is performed at 7 to 15 days interval. After laparotomy, the plastic bag is removed. The right artery, bile duct and hepatic vein are sectioned and the tumoral liver is removed. Drain was placed at the resection surface, and the abdomen is closed. ALPPS can enable curative resection of hepatic metastasis in patients with tumors previously considered non-resectable. The aim of this manuscript was to describe the indications and technical aspects of ALPPS in relation to the first case carried out in our city, in a 47-year-old woman with advanced gallbladder cancer with bilobar metastases.

Autorregulação encefálica na insuficiência hepática fulminante antes e após transplante hepático / Cerebral autoregulation in fulminant hepatic failure before and after liver transplantation

O presente estudo avaliou a autorregulação encefálica (ARE) em doentes com insuficiência hepática fulminante (IHF) antes e após transplante hepático. Foram avaliados 25 pacientes com diagnóstico de IHF, 17 foram avaliados antes e após o transplante hepático, sendo seis (24,0%) do sexo masculino e 19 (76,0%) feminino. A média de idade foi de 33,8 anos, que variou de 14 a 56 anos, com desvio padrão de 13,1 anos. A hemodinâmica encefálica foi avaliada pela velocidade de fluxo sanguíneo encefálico (VFSE) nas artérias cerebrais médias e artéria basilar (AB), que usou o ultrassom Doppler transcraniano (DTC), dispositivo de dois canais, com transdutores de 2 mega Hertz (MHz). A autorregulação encefálica foi mensurada pelo índice de autorregulação (IARE) estática que leva em conta os efeitos do aumento da pressão arterial média (PAM) sobre a VFSE. Para isso, promoveu-se o aumento da PAM (20 mmHg a 30 mmHg) com infusão de noradrenalina.. Ao se avaliar o IARE considerando a velocidade de fluxo sanguíneo em quatro momentos (pré-transplante, 1°, 2° e 3° dia após o transplante), observou-se que houve diferença estatística em artéria cerebral média (ACM) à direita (p=0,008), esquerda (p=0,007), máxima (p=0,005), e AB (p=0,006); assim como na análise em cada tempo do IARE, observou-se diferença estatística em ACM à direita (p=0,012), esquerda (p=0,009), máxima (p=0,006), e AB (p=0,011). A análise categórica do IARE na artéria cerebral média e basilar descreveu que a maioria dos doentes reestabeleceu a AR no 2° dia em ACM e 3° na AB (índice > 0,6), enquanto com o índice > 0,8 em ambas as artérias a ARE reestabeleceu no 2° dia. As variáveis sistêmicas como pressão parcial de CO2 e hemoglobina nos tempos da avaliação não apresentaram diferença estatística p=0,100 e p=0,093 respectivamente. Os resultados obtidos apontam para o comprometimento da ARE antes e após transplante hepático, tanto em circulação anterior como posterior, e que tende a ser reestabelecido entre 48...

This study evaluated cerebral autoregulation in patients with fulminant hepatic failure (FHF) before and after liver transplantation. A total of 25 patients comprising six (24.0%) males and 19 (76.0%) females with FHF were evaluated. Seventeen patients were evaluated both before and after liver transplantation. Mean age of the patients was 33.8 years, with a range of 14-56 years and standard deviation of 13.1 years. Brain hemodynamics was assessed by cerebral blood flow velocity in the middle cerebral arteries (MCA) and basilar artery (BA) using transcranial Doppler ultrasound on a two-channel device with 2 MHz transducers. Cerebral autoregulation was measured by static cerebral autoregulation index (SCAI), which accounts for the effects of increase in mean arterial blood pressure (ABP) on cerebral blood flow velocity. An increase in ABP (20 mmHg to 30 mmHg) was induced with norepinephrine infusion. Evaluation of SCAI based on blood flow velocity (BVF) at four timepoints (pre-transplant and on 1st, 2nd and 3rd days post-transplant) revealed a statistical difference in the MCA right (p = 0.008) left (p = 0.007), maximum (p = 0.005) and the BA (p = 0.006). In addition, analysis by timepoint showed a statistical difference in MCA (p = 0.012), left (p = 0.009), maximum (p = 0.006) and in the BA (p = 0.011). Categorical analysis of autoregulation in the MCA and BA showed that most patients reestablished autoregulation in the MCA on the 2nd day post-transplant and in the BA (index > 0.6) on the 3rd day, while autoregulation was reestablished in both arteries (index > 0.8) on the 2nd day. On the assessment by timepoint, the systemic variables CO2 partial pressure and hemoglobin showed no statistically significant differences (p = 0.100 and p = 0.093, respectively). The results reveal impaired SCAI before and after liver transplantation, both in anterior and posterior circulation, with a tendency to reestablish at 48 to72 hours. The findings of this study can help...

Insuficiencia hepática aguda fulminante por virus de la hepatitis B: reporte de caso / Acute liver failure due to hepatitis B: a case report

Se reporta el caso de una mujer de 37 años de edad sin antecedentes relevantes, que consulta por cuadro febril ictérico asociado con alteración hepática importante con patrón necroinflamatorio, se documenta hepatitis viral B y presenta una evolución tórpida rápida hasta la muerte. De esta forma, se exponen los posibles factores que influyen en la progresión hacia la insuficiencia hepática fulminante (IHF) descritos en la literatura.

We report the case of a 37 year old woman who came to the hospital because of jaundice and a fever. Her symptoms were associated with significant liver impairment and a necroinflammatory pattern due to viral hepatitis B although she had no relevant medical history. Her symptoms developed rapidly until death. We present the factors that may have influenced her progression to fulminant liver failure as described in the literature.

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft / Técnica simplificada para transplante auxiliar ortotópico de fígado utilizando um enxerto inteiro

BACKGROUND: Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. AIM: To describe an alternative technique to auxiliary liver transplant on acute liver failure. METHOD: Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. RESULTS: The procedure improved liver function and decreased intracranial hypertension in the postoperative period. CONCLUSION: This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. .

RACIONAL: A insuficiência hepática aguda está associada à alta taxa de mortalidade e os principais efeitos do tratamento são para evitar o edema cerebral e as infecções, que muitas vezes são responsáveis pela morte do paciente. O transplante hepático é o tratamento padrão-ouro e melhora a sobrevida de um ano. OBJETIVO: Descrever uma técnica alternativa para transplante de fígado auxiliar na insuficiência hepática aguda. MÉTODO: Transplante de fígado auxiliar devido à insuficiência hepática fulminante pela infecção pelo vírus da hepatite B. O paciente preencheu os critérios O´Grady e o racional para indicar o transplante de fígado auxiliar foi a hepatite aguda sem instabilidade hemodinâmica ou insuficiência renal em um paciente com deterioração da consciência. Foi realizado o transplante auxiliar de fígado com enxerto inteiro com uma técnica alternativa para transplante auxiliar parcial de fígado. RESULTADOS: O procedimento demonstrou melhora da função hepática e diminuição da hipertensão intracraniana no pós-operatório. CONCLUSÃO: Esta técnica é viável e pode superar algumas complicações pós-operatórias que estão associadas com enxertos parciais. Tanto quanto sabemos, este é o primeiro caso de transplante de fígado auxiliar descrito no Brasil. .

Perfil biológico y social de la población trasplantada en el hospital Garrahan por hepatitis fulminante y su relación con la evolución postrasplante / Biological and social profile of patients who underwent liver transplantation because of acute liver failure at the Garrahan Hospital

El objetivo de este estudio fue describir el perfil biológico y social del paciente pediátrico con trasplante hepático por insuficiencia hepática aguda (IHA) y la evolución postrasplante. Material y Método: trabajo retrospectivo, descriptivo y observacional, se revisaron la base de datos de 142 pacientes trasplantados por IHA desde 1992 al 2008. Se describieron los datos demográficos y sociales, indicaciones de trasplante, tipo de injerto utilizado, compatibilidad del grupo ABO, evolución pos trasplante (resultados primarios), complicaciones del trasplante y sobrevida. Resultados: El 51% de los casos de IHA fue asociado a la hepatitis infecciosa por virus A (HAV) y el 41% correspondió a las IHA indeterminadas. El 85% de la población trasplantada (120 casos) recibió un donante de tipo cadavérico (DC) y la compatibilidad de grupo ABO fue del 85%. Las complicaciones más frecuentes fueron: biliares 33 casos, infecciones bacterianas 20 casos y vasculares 13 casos. El rechazo agudo estuvo presente en 72 casos mientras que el rechazo crónico se diagnosticó en 7 casos. La sobrevida de la IHA al año del postrasplante fue del 80% y a los 5 y 10 años fue del 77%. La conciencia de enfermedad reflejada en el cumplimiento de las consignas médicos sociales estuvo presente en un 86,25%. El 70% de los padres de los niños trasplantados eran biológicos y el 52% de la población provino del área centro (Buenos Aires, Córdoba, Entre Ríos, y Santa Fe). La cobertura estuvo a cargo del estado en el 45% de la muestra (AU)

The aim of this study was to describe the social and biological profile of pediatric patients who undergo liver transplantation because of acute liver failure (ALF) and post-transplant outcome. Material and Methods: A retrospective, descriptive, and observational study was conducted. The database of 142 patients who underwent liver transplantation because of ALF between 1992 and 2008 was reviewed. Demographic and social features, indication for transplantation, type of graft used, ABO group compatibility, post-transplant outcome (primary results), complications of the transplantation and survival were evaluated. Results: ALF was associated with infectious hepatitis A (HAV) in 51% of the cases and with indeterminate ALF in 41%. Overall, 85% of the transplanted patients (120 cases) received a deceased donor (DD) organ and ABO group compatibility was 85%. Most common complications were: biliary in 33 cases, bacterial infections in 20 cases, and vascular in 13 cases. Acute rejection was observed in 72 cases while chronic rejection was diagnosed in seven cases. Oneyear post-transplant survival after ALF was 80%, while 5- and 10-year survival was 77%. Disease awareness expressed in compliance with medical and social indications was observed in 86%. Seventy percent of the parents of transplanted children were there biological parents and 52% of the population came from the central area of the country (Buenos Aires, Córdoba, Entre Ríos, y Santa Fe). Forty-five percent of the sample had public health care coverage (AU)

Abordagem inicial à insuficiência hepática aguda / Initial approach to acute hepatic insufficiency

A insuficiência hepática aguda é uma entidade clínica rara cujo reconhecimento precoce é crucial para a instituição de medidas e transferência do paciente para centro de transplante hepático emergencial. O objetivo deste artigo é revisar tópicos diagnósticos e o tratamento inicial da insuficiência hepática aguda.

Acute liver failure is a rare critical illness whose early recognition is crucial for the establishment of management measures and to proceed the patient transference to a center with active emergency liver transplantation program. The purpose of this article is to review basic topics of diagnosis and initial treatment of acute liver failure.

[Liver cell therapy in the treatment of inborn errors of metabolism in children]. / Terapia celular hepática en el tratamiento de las metabolopatías congénitas en niños.

Liver transplantation has been remarkably effective in the treatment of patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the main limitation, resulting in longer waiting times and an increase in the mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation. Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients, a bridge to restore liver function or liver transplant. The procedure consists in transplanting individual cells in a recipient organ in enough quantity to survive and restore the function. The capacity of hepatic regeneration constitutes the biological basis of hepatocyte transplantation. Liver cell transplantation is carried out by means of the isolation of hepatocytes from donor liver rejected for orthotopic transplantation, to prepare a cell suspension for infusion, cryopreservation and, finally, hepatocytes are implanted into the recipient. This may be an optional therapeutic procedure in some patients with inborn errors of metabolism, fulminant hepatic failure, and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. The first hepatocyte transplantation in Spain was performed in the Cell Therapy Unit of the Hospital La Fe of Valencia, creating a new research line in the transplant program.

La introducción de la vacuna contra la hepatitis A en el Calendario Nacional de Vacunación: una nueva realidad / Hepatitis A immunisation in the argentinean mandatory schedule

La hepatitis A (HA) presenta una evolución benigna, pero en ocasiones puede causar una insuficiencia hepática aguda con necesidad de trasplante. En 2003, en un consenso realizado en la Sociedad Argentina de Pediatría, se recomendó la incorporación de la vacuna contra la HA en el calendario nacional. Esto se concretó por decreto ministerial y se efectivizó a partir del 1 de junio de 2005, con la obligación de aplicar una dosis de la vacuna a todos los niños al año de edad. Desde entonces, se registró una disminución marcada de casos y no se documentaron cuadros de insuficiencia hepática aguda desde el año 2006. Los estudios de seguimiento mostraron, hasta el momento, una circulación viral baja y la persistencia de anticuerpos hasta los 5 años posteriores a su introducción.

Hepatitis A (HA) presents a benign evolution, but occasionally some patients develop a more severe disease. Previously to 2005 hepatitis A was an important cause of acute liver failure (ALF) and hepatic transplant. In 2003, a consensus in the Argentinian Pediatrics Society was done; it had just recommended the inclusion of the vaccine in the mandatory immunisation schedule. This was issued by the Health Ministery, and was applied on June 1st, 2005. The schedule was one dose at the age of one year of age. Since then, an important reduction of HA was registered, without any case of ALF since 2006. Follow-up studies so far showed low viral circulation and persistence of antibodies to 5 years later.

La introducción de la vacuna contra la hepatitis A en el Calendario Nacional de Vacunación: una nueva realidad / Hepatitis A immunisation in the argentinean mandatory schedule

La hepatitis A (HA) presenta una evolución benigna, pero en ocasiones puede causar una insuficiencia hepática aguda con necesidad de trasplante. En 2003, en un consenso realizado en la Sociedad Argentina de Pediatría, se recomendó la incorporación de la vacuna contra la HA en el calendario nacional. Esto se concretó por decreto ministerial y se efectivizó a partir del 1 de junio de 2005, con la obligación de aplicar una dosis de la vacuna a todos los niños al año de edad. Desde entonces, se registró una disminución marcada de casos y no se documentaron cuadros de insuficiencia hepática aguda desde el año 2006. Los estudios de seguimiento mostraron, hasta el momento, una circulación viral baja y la persistencia de anticuerpos hasta los 5 años posteriores a su introducción.(AU)

Hepatitis A (HA) presents a benign evolution, but occasionally some patients develop a more severe disease. Previously to 2005 hepatitis A was an important cause of acute liver failure (ALF) and hepatic transplant. In 2003, a consensus in the Argentinian Pediatrics Society was done; it had just recommended the inclusion of the vaccine in the mandatory immunisation schedule. This was issued by the Health Ministery, and was applied on June 1st, 2005. The schedule was one dose at the age of one year of age. Since then, an important reduction of HA was registered, without any case of ALF since 2006. Follow-up studies so far showed low viral circulation and persistence of antibodies to 5 years later.(AU)

Terapia com células da medula óssea em modelo experimental de insuficiência hepática aguda induzida por acetominofen / Therapy with bone marrow cells in an experimental model of heart failure liver induced by acute acetaminophen

Introdução e objetivos: a insuficiência hepática aguda (IHA), apesar de rara, permanece como uma condição rapidamente progressiva e frequentemente fatal. A intoxicação por acetaminofen (APAP) induz necrose hepática maciça e frequentemente leva à morte por edema cerebral. Terapias celulares são de grande interesse como potenciais tratamentos para IHA. Neste projeto foi avaliado o potencial terapêutico das células mononucleares da medula óssea (CMMO) em um modelo experimental de IHA induzida por APAP em camundongos. Métodos: A IHA foi induzida em camundongos C57Bl/6, previamente submetidos à dieta alcoólica por três semanas, através da administração de APAP na dose de 300 mg/kg por via intraperitoneal. Após a indução da IHA, os camundongos foram transplantados, por via endovenosa, com 107 CMMO...

Introduction and objectives: a cute liver failure (IHA), although rare, remains a rapidly progressive and often fatal condition. Poisoning by acetaminophen (APAP) induces a massive hepatic necrosis and often leads to death by cerebral edema. Cell therapies are of great interest as potential treatments for IHA. In this project we evaluated the therapeutic potential of bone marrow mononuclear cells (BMC) in an experimental model of IHA induced by APAP in mice. Methods: The IHA was induced in C57BL/6 mice previously submitted to the alcohol diet for three weeks by the administration of APAP at a dose of 300 mg / kg, intraperitoneally. After induction of IHA, the mice were transplanted intravenously with 107 BMC...