Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children / Expresión de miR-let7b y miR-19b en niños con colestasis intrahepática familiar progresiva (PFIC)

Background MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. Methods 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. Results qPCR on PFIC patients’ samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. Conclusion In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future (AU)

Antecedentes Los microRNA (miRNA) son un grupo de pequeños RNA no codificantes que se unen al ARNm diana y regulan la expresión génica. Recientemente se han investigado los microRNA circulantes como marcadores de enfermedades y dianas terapéuticas. Aunque varios estudios analizan la expresión de miRNA en enfermedades hepáticas, estos estudios sobre PFIC son escasos. La colestasis intrahepática familiar progresiva (PFIC) es una enfermedad hepática rara con herencia autosómica recesiva. La mayoría de los niños con PFIC progresan a cirrosis e insuficiencia hepática y, en consecuencia, requieren de un trasplante de hígado. El objetivo de este trabajo es la investigación de los niveles de expresión de miR-19b y miR-17b en niños iraníes con PFIC. Métodos Se consideraron 25 pacientes con PFIC, 25 niños sanos y 25 pacientes con atresia biliar como grupos de casos y controles. Se obtuvieron muestras de sangre y se midieron las pruebas de función hepática (LFT). Después de la extracción de RNA y la síntesis de cDNA, se realizó PCR cuantitativa usando cebadores específicos para miR-19b y miR-17b. El gen U6 se utiliza como control interno. Resultados La qPCR en muestras de pacientes con PFIC demostró que la expresión de miR-19b y miR-17b disminuyó significativamente en los pacientes en comparación con dos grupos de control, con un valor de p<0,0001 y un valor de p=0,0006, receptivamente. Conclusión En conclusión, los micro-RNA circulantes, como miR-19b y miR-let7b, tienen una oportunidad potencial de ser un marcador de diagnóstico no invasivo o un objetivo terapéutico para PFIC en el futuro (AU)

Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children.

BACKGROUND: MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. METHODS: 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. RESULTS: qPCR on PFIC patients' samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. CONCLUSION: In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future.

Insuficiencia hepática secundaria a enfermedad poliquística renal-hepática

La enfermedad poliquística renal autosómica dominante es considerada la enfermedad renal genética más frecuente y es la cuarta causa de enfermedad renal crónica a nivel mundial. Afecta a cerca de 1 por cada 1000 nacidos vivos. La enfermedad poliquística hepática es la manifestación extrarrenal más frecuente de la enfermedad poliquística renal. La cirrosis hepática constituye un hallazgo tardío en esta enfermedad y su presentación es más común en el anciano, y la descompensación de la enfermedad con insuficiencia hepática como causa de muerte. Presentamos el caso de un paciente masculino de 60 años con antecedentes patológicos personales de la enfermedad poliquística renal con ascitis a tensión, y edemas en ambos miembros inferiores con datos de insuficiencia hepática y evolución desfavorable hasta su fallecimiento. Aunque la presencia de la falla hepática se asocia a un pronóstico precario, la detección precoz puede suponer el inicio de un tratamiento oportuno y apropiado que puede ser beneficioso.

Autosomal dominant polycystic kidney disease is considered the most common genetic kidney disease and the fourth leading cause of chronic kidney disease worldwide. It affects about 1 in 1,000 live births. Polycystic liver disease is the most common extrarenal manifestation of polycystic kidney disease. Liver cirrhosis is a late finding in this disease and its presentation is more common in the elderly. Decompensation of the disease, with liver failure as the cause of death, is rare in polycystic liver disease. We report the case of a 60-year-old male patient with a personal pathological history of polycystic kidney disease with tense ascites and edema in both lower limbs, with evidence of liver failure and unfavorable evolution until his death. Although the presence of liver failure is associated with poor prognosis, its early detection may mean the initiation of timely and appropriate treatment that may be beneficial.

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.

Falla hepática aguda sobre crónica / Acute on chronic liver failure

La falla hepática aguda sobre crónica (ACLF) es un síndrome que se presenta en pacientes con cirrosis descompensada, y se caracteriza por una mortalidad elevada a 28 días, que se diagnostica con la combinación de falla hepática y extrahepática. Se han publicado numerosas definiciones, de las cuales se resalta la realizada por la Asociación Europea para el Estudio del Hígado (EASL), la cual tiene en cuenta 6 sistemas orgánicos (hígado, riñón, pulmón, cerebro, coagulación y circulación), y gradúa su gravedad basada en el número de sistemas comprometidos en el momento de la presentación. Entre los pilares en el abordaje del paciente con ACLF es imperiosa la búsqueda de los factores precipitantes, siendo los más frecuentes las infecciones bacterianas, el consumo excesivo de alcohol, la hemorragia de vías digestivas, la injuria hepática inducida por medicamentos y la cirugía hepática o cirugía mayor, teniendo en cuenta que aproximadamente en el 50 % de los casos no se logrará establecer la causa. Los pilares angulares del tratamiento constarán de la reversión o interrupción del factor precipitante, el soporte orgánico y, en aquellos pacientes que cumplan los criterios para trasplante, su realización oportuna.

Acute-on-chronic liver failure is a syndrome that occurs in patients with acute decompensated cirrhosis and is characterized by high 28-day mortality that is diagnosed with a combination of hepatic and extrahepatic organ failure. Numerous definitions have been published with great concern related to the etiology and cause of the decompensation, of which the one made by the European Association for the Study of the Liver (EASL) stands out, taking into account 6 organic systems (liver, kidney, lung, brain, coagulation, and circulation), and grades its severity based on the number of systems involved at the time of presentation. Among the pillars in the approach to the patient with ACLF, the search for precipitating factors is imperative, the most frequent being bacte-rial infections, excessive alcohol consumption, digestive tract bleeding, drug-induced liver injury, liver surgery or major surgery, keeping in mind that in approximately 50% of cases the cause will not be established. The cornerstones of treatment will consist of the reversal or interruption of the precipitating factor, organ support and, in those patients who meet the criteria for transplantation, its timely performance.

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.

Diagnósticos de enfermagem em pacientes com cirrose hepática em um serviço hospitalar de emergência / Nursing diagnoses in patients with liver cirrhosis in an emergency hospital service

Introdução: O estudo foi desenvolvido com o intuito de destacar a importância dos diagnósticos de enfermagem em pacientes cirróticos, em decorrência do aumento de casos de doenças hepáticas. Objetivo: Descrever as variáveis sociodemográficas e clínicas e elencar os diagnósticos de enfermagem da Associação Norte-Americana de Diagnósticos de Enfermagem (NANDA-I) em pacientes com cirrose hepática atendidos em uma emergência hospitalar. Material e Métodos: Pesquisa quantitativa, descritiva e transversal, realizada com 59 pacientes atendidos em uma emergência de um hospital universitário no sul do Brasil, no período de abril a junho de 2018. Resultados: Prevaleceu durante a pesquisa a população do sexo masculino com 66,1% e de baixo nível educacional, tendo o álcool como principal etiologia da doença com 44,1% e a presença de comorbidades como a hipertensão com 14,8% e o diabetes com 15,6%. Foram identificados seis diagnósticos de enfermagem com maior prevalência: risco de infecção, risco de desequilíbrio eletrolítico, nutrição desequilibrada (menor do que as necessidades corporais), dor aguda, volume de líquidos excessivo e risco de sangramento. Conclusão: As características sociodemográficas apresentadas neste estudo corroboram os achados já amplamente conhecidos em doença hepática. Os diagnósticos de enfermagem identificados foram condizentes com as repercussões fisiopatológicas da cirrose hepática, destacando-se o predomínio dos diagnósticos de risco.

Introduction: The study was developed with the aim of highlighting the importance of nursing diagnoses in cirrhotic patients, due to the increase in cases of liver disease. Objective: Describe the sociodemographic and clinical variables and list the nursing diagnoses of the North American Association of Nursing Diagnoses (NANDA-I) in patients with liver cirrhosis treated in a hospital emergency. Material and Methods: Quantitative, descriptive and cross-sectional research, conducted with 59 patients seen in an emergency department of a university hospital in southern Brazil, from April to June 2018. Results: There was a predominance during the research of the male population with 66.1% and of low educational level, with approximately 54.2% having completed elementary school, with alcohol as the main etiology of the disease with 44.1% and the presence of comorbidities such as hypertension with 14.8% and diabetes with 15.6%. Six nursing diagnoses with higher prevalence were identified: risk of infection, risk of electrolyte imbalance, unbalanced nutrition (less than body needs), acute pain, excessive fluid volume and risk of bleeding. Conclusion: The sociodemographic characteristics presented in this study corroborate the already widely known findings in liver disease. The nursing diagnoses identified were consistent with the pathophysiological repercussions of liver cirrhosis, highlighting the predominance of risk diagnoses.

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.

Hígado y SARS-CoV-2: aspectos claves de la literatura / Liver and SARS-CoV-2: Literature key aspects

Resumen El nuevo coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2), virus que se ha expandido por todo el mundo, produce una infección respiratoria aguda capaz de producir la muerte; sin embargo, el daño en otros órganos también es frecuente. Diversos estudios han evidenciado alteraciones en pruebas de lesión hepáticas, las cuales se han asociado con enfermedad grave y mayor estancia hospitalaria; así mismo, en la infección por el virus en pacientes con enfermedad hepática preexistente se observó una elevación significativa de las aminotransferasas durante el curso de la enfermedad y mayor riesgo de enfermedad grave. La explicación fisiopatológica de la afectación hepática en estos pacientes abarca el efecto citopático directo producido por la unión del virus a la enzima convertidora de la angiotensina II (ECA-II) a los hepatocitos y colangiocitos, una respuesta inmunitaria desproporcionada y, en algunos casos, la hepatotoxicidad por medicamentos.

Abstract The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that has spread around the world, causes an acute respiratory infection and it may also cause death. The damage that can cause in other organs is frequent. Many studies had also shown alterations in liver function tests, that are then related to serious illness and with hospitalization requirements. Moreover, in patients infected with the virus that had underlying liver disease, a significant increase in the level of aminotransferases was observed in the course of the disease. A greater risk of serious illness was also detected. The pathophysiological explanation of liver injury in those patients covers the direct cytopathic effect produced by binding the virus, the angiotensin-converting enzyme (ACE2) to the hepatocytes and the cholangiocytes, excessive immune response, and in some cases, drug-induced hepatotoxicity.

Intoxicación aguda por acetaminofén en atención primaria / Acute Acetaminophen Intoxication in Primary Care / Intoxicação aguda por acetaminofeno na atenção primária

Resumen: El acetaminofén es un medicamento analgésico y antipirético considerado como seguro y eficaz. Debido a esto, en Colombia es de venta libre y ampliamente utilizado tanto en niños como en adultos. Por su fácil acceso, la intoxicación por acetaminofén es un evento frecuente, por lo que los médicos de atención primaria deben tener conocimiento acerca de su diagnóstico y manejo, además de los factores de riesgo para el desarrollo de falla hepática y las indicaciones para remitir a los pacientes a los servicios especializados. El objeto de este artículo es orientar al personal de atención primaria en salud acerca de la fisiopatología, el diagnóstico y el tratamiento de esta intoxicación.

Abstract: Acetaminophen is an analgesic and antipyretic medication considered safe and effective. Because of this, in Colombia it is freely available and widely used in both children and adults. Due to its easy access, acetaminophen intoxication is a frequent event, so primary care physicians must be knowledgeable about its diagnosis and management. In addition to the risk factors for the development of liver failure and the indications for referring patients to specialized services. The purpose of this article is to guide primary health care personnel about the pathophysiology, diagnosis and treatment of this intoxication.

Resumo: O acetaminofeno é um medicamento analgésico e antipirético considerado seguro e eficaz. Por isso, na Colômbia é over-the-counter e amplamente utilizado em crianças e adultos. Por seu fácil acesso, a intoxicação por acetaminofeno é um evento frequente, é por isso que os médicos da atenção primária devem estar cientes de seu diagnóstico e manejo. Além dos fatores de risco para o desenvolvimento de insuficiência hepática e indicações de encaminhamento aos pacientes para serviços especializados. O objeto deste artigo é guiar á equipe da atenção primária á saúde sobre a fisiopatologia, diagnóstico e tratamento dessa intoxicação.

Síndrome hepatorrenal en falla hepática aguda sobre crónica / Hepatorrenal syndrome in acute on chronic hepatic failure

Resumen La insuficiencia hepática aguda sobre crónica (ACLF, por su nombre en inglés: Acute-on-Chronic Liver Failure) es una entidad de reciente caracterización que se presenta como una descompensación aguda de una hepatopatía crónica, la cual puede ir asociada a falla en diferentes órganos y presentar una alta mortalidad. Su incidencia alcanza hasta un 30% de pacientes que consultan por complicaciones asociadas a cirrosis de base. Dentro de los factores precipitantes más frecuentes se encuentran las infecciones bacterianas, el alcoholismo y la reactivación de hepatitis virales; no obstante, hasta en un 40% de los casos no se identifica ningún factor precipitante. La fisiopatología de esta entidad aún es desconocida en cierta medida, pero se plantea la existencia de una respuesta inflamatoria excesiva en su desarrollo. No existe ningún tratamiento específico y su manejo se basa en el tratamiento para complicaciones asociadas, soporte y finalmente trasplante hepático. La disfunción renal es un hallazgo común en pacientes con enfermedad hepática. Se pensaba que el síndrome hepatorrenal era de carácter meramente funcional. Ahora, ante la evidencia de algún grado de daño tubular relacionado, se ha mejorado la comprensión de la fisiopatología de dicha entidad, lo que ha obligado recientemente a replantear los criterios diagnósticos y la clasificación de la enfermedad. Describimos el caso clínico de una paciente atendida en un centro hospitalario en la ciudad de Pereira, Risaralda. Ella presentó bacteriemia por cocos Gram positivos de origen no claro, lo que se consideró como el factor precipitante; tuvo deterioro clínico, con aparición de síndrome hepatorrenal y falla multiorgánica, lo que finalmente la llevo a la muerte, a pesar del manejo multidisciplinario.

Abstract Acute-on-chronic liver failure (ACLF) is a recently characterized entity that presents as an acute decompensation of chronic liver disease. It can be associated with failure in different organs and presents a high mortality rate. Its incidence reaches up to 30% on patients consulting for complications derived from cirrhosis. Among the most frequent precipitating factors, there are bacterial infections, alcoholism, and reactivation of viral hepatitis; however, in up to 40% of the cases, no precipitating factor is identified. The pathophysiology of this entity is still unknown to a certain extent, but the existence of an excessive inflammatory response in its development is suggested. There is no specific treatment and its management is based on treatment for associated complications, support, and finally liver transplantation. Kidney dysfunction is a common finding in patients with liver disease. The understanding of the pathophysiology of this entity, previously thought to be purely functional in nature, yet now given the evidence of some degree of related tubular damage, has improved and has recently entailed a rethink of the diagnostic criteria and the classification of the illness. We describe the clinical case of a patient treated at a hospital in the city of Pereira, Risaralda, who presented bacteremia due to Gram-positive cocci of unclear origin, considered as the precipitating factor. The patient had clinical deterioration, as well as the onset of hepatorenal syndrome and multi-organ failure, finally leading to death despite multidisciplinary treatment.

Breviario de guías y metas del paciente crítico hospitalizado en Medicina Interna / Breviary of guidelines and goals of critical hospitalized patients in Internal Medicine

Los pacientes en estado crítico presentan disfunción fisiológica que provoca inestabilidad en órganos y sistemas del cuerpo, con desenlaces fatales y lesiones irreversibles o incluso la muerte. En los servicios de Medicina Interna de los hospitales de México, en especial en los públicos, hay pacientes críticos con múltiples patologías que requieren vigilancia en el cumplimiento de diversas metas de su tratamiento. Se presenta un compendio de las guías y metas de patologías críticas con mayor prevalencia en los servicios de Medicina Interna, las cuales son necesarias para guiar el tratamiento.

Patients with critical illness develop physiological dysfunction which provokes multi-organ system failure and triggers fatal outcomes and irreversible injuries or even death. Inside Internal Medicine services of Mexican hospitals, especially in public hospitals, there is a considerable number of critically ill patients with multiple pathologies who require surveillance to reach clinical goals of their treatment. We present a summary of guidelines and goals of the most prevalent critical diseases inside Internal Medicine services, which are necessary to guide treatments.

Insuficiência hepática crônica agudizada está independentemente associada com menor sobrevida em pacientes com peritonite bacteriana espontânea / Acute-on-chronic liver failure is independently associated with lower survival in patients with spontaneous bacterial peritonitis

ABSTRACT BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a decompensation of cirrhosis with an in-hospital mortality ranging from 20% to 40%. OBJECTIVE: The purpose of this study is to analyze if EASL-CLIF definition of acute-on-chronic liver failure (ACLF) is able to predict mortality in cirrhotic patients with SBP. METHODS: Historical cohort study conducted in a public tertiary care teaching hospital. Data from medical records from January 2009 to July 2016 were obtained by searching the hospital electronic database for samples of ascites collected in the period. Electronic and physical medical records were analyzed and patients were included if they were over 18-years old, with cirrhosis and an ascites fluid compatible with SBP: 69 patients were included. Liver-specific scores were calculated and Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis. RESULTS: All cause mortality was 44%, 56.5% and 74% for 28-, 90- and 365-day, respectively. The prevalence of ACLF was 58%. Of these, 65% grade 1, 17.5% grade 2 and 17.5% grade 3. In multivariate analysis, the use of proton-pump inhi­bitors, alanine transaminase lower than 40 U/L, hemoglobin higher than 9 g/dL, absence of ACLF and lower CLIF-SOFA and MELD scores were independently associated with higher survival for both 28- and 90-day interval. CONCLUSION: The presence of ACLF and higher CLIF-SOFA scores were independently associated with higher 28- and 90-day mortality in cirrhotic patients admitted due to SBP.

RESUMO CONTEXTO: A peritonite bacteriana espontânea (PBE) é uma descompensação da cirrose com uma mortalidade intra-hospitalar de 20% a 40%. OBJETIVO: O objetivo deste estudo é analisar se a definição de insuficiência hepática crônica agudizada (IHCA) como definido pelo consórcio EASL-CLIF é capaz de predizer mortalidade em pacientes cirróticos com PBE. MÉTODOS: Coorte histórica conduzida em um hospital de ensino público terciário. Foram obtidos dados de prontuários médicos de janeiro de 2009 até julho de 2016, buscando no banco de dados eletrônico do hospital por todas as amostras de ascite coletadas no período. Prontuários eletrônicos e físicos foram analisados e os pacientes com mais de 18 anos com cirrose e líquido de ascite compatível com PBE foram incluídos. Foram incluídos 69 pacientes. Escores específicos para o fígado foram calculados e a análise de sobrevida de Kaplan-Meier foi utilizada para a análise univariada, e uma abordagem progressiva para a regressão logística de Cox foi usada para a análise multivariada. RESULTADOS: A mortalidade por todas as causas foi 44%, 56,5% e 74% para 28-, 90- e 365-dias, respectivamente. A prevalência de IHCA foi de 58%. Desses, 65% grau 1, 17,5% grau 2 e 17,5% grau 3. Na análise multivariada, o uso de inibidores da bomba de prótons, alanina transaminase menor que 40 U/L, hemoglobina acima de 9 g/dL, ausência de IHCA e menores valores dos escores CLIF-SOFA e MELD foram independentemente associados com maior sobrevida para ambos intervalos de 28- e 90-dias. CONCLUSÃO: A presença de IHCA e maiores valores de CLIF-SOFA foram independentemente associados em maior mortalidade para pacientes cirróticos admitidos por PBE no intervalo de 28- e 90-dias.

Hepatitis aguda por virus E. Presentación de dos casos con evolución clínica diferente / Acute hepatitis due to E virus. Presentation of two cases with different clinical evolution

RESUMEN El virus de la hepatitis E tiene una amplia distribución a nivel mundial. Se presentaron dos casos clínicos en la provincia de Matanzas, con diagnóstico confirmado de hepatitis E mediante la determinación del ARN viral en heces fecales congeladas; a pesar de proceder de áreas de salud distantes, coincidieron en el mismo período de tiempo. El primero de ellos, una gestante asintomática diagnosticada fortuitamente a partir de elevación de enzimas hepáticas de citolisis. Evolucionó satisfactoriamente sin repercusión en su bienestar materno, trasmisión fetal, ni complicaciones perinatales. El segundo, una paciente portadora de síndrome metabólico, con evolución tórpida de su cuadro infeccioso viral, que la llevó a la insuficiencia hepática y a la muerte. Con estos casos se reflejó el amplio espectro de esta enfermedad en cuanto a formas clínicas de presentación y evolución. Se demostró que pueden ocurrir complicaciones en cualquier grupo poblacional, de ahí la importancia de considerarla en el diagnóstico diferencial de las enfermedades infecciosas hepáticas (AU).

ABSTRACT Hepatitis E virus is widely distributed around the world. Two clinical cases occurring in the province of Matanzas were presented, both with diagnosis of E hepatitis confirmed through viral RNA determination in frozen stool; although patients came from faraway health areas, they coincided in the same time period. The first patient, a pregnant asymptomatic woman, was incidentally diagnosed due to an increase of cytolysis liver enzymes. Her evolution was satisfactory without repercussion on maternal wellbeing, fetal transmission, nor perinatal complications. The second patient, a metabolic syndrome carrier, had torpid evolution of a viral infectious disease leading her to liver failure and death. These cases highlighted the wide range of this disease according to its clinical forms of presentation and evolution. It was showed that complications may occur in any population group, in consequence it is important to consider this disease when making the differential diagnosis of liver infectious diseases (AU).

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.

Avaliação da mortalidade no pós-operatório de fraturas de fêmur em idosos com comorbidades prévias / Evaluation of postoperative mortality of femoral fractures in elderly with previous comorbidities

Introdução: Queda é o acidente que ocorre com maior frequência no idoso, sendo a principal causa de morte naqueles com mais de 65 anos. As fraturas do quadril ocupam um papel de grande importância, gerando grande problema de ordem clínica envolvendo pacientes e familiares e de ordem econômica para a sociedade. Objetivo: Coletar dados de questionário da admissão e correlacionar a presença de comorbidades prévias a mortalidade em 30 dias do pós-cirurgia. Métodos: Estudo retrospectivo observacional não randomizado com 216 pacientes com fraturas cirúrgicas do quadril com 61 anos ou mais de idade atendidos no setor de emergência do Centro Hospitalar São Lucas na cidade de Niterói, RJ, no período de 30/03/2016 a 20/03/2018. Resultados: A incidência de óbito após a cirurgia do quadril é igual a 6,9% no primeiro mês. O paciente com fratura no quadril tem comorbidades cardiovasculares (75,9%). O óbito está associado à comorbidade hepática em 13,3% e ao baixo peso em 33,3%. O fato de ter duas ou mais comorbidades não está significativamente associado ao óbito. Conclusão: As comorbidades hepáticas, o baixo peso e a presença de disfunções cardiovasculares são importantes preditores prognósticos na mortalidade do paciente com mais de 61 anos após cirurgia de fratura do fêmur no primeiro mês. (AU)

Introduction: Falls are the leading cause of accidents and death in those aged 65 and above. The high incidence of these injuries impact patients, their families and it represents an economic problem for society. Objective: Collect data from the admission survey and correlate previous comorbidities to mortality in 30 days after surgery. Methods: Retrospective observational non-randomized study. 216 patients were included, aged 61 years or older, who were admitted at the emergency department of the Centro Hospitalar São Lucas in Niterói city, Rio de Janeiro. All the participants were candidates of hip fracture surgery between 03/30/2016 and 03/20/2018. Results: The mortality after hip surgery was 6.9% in the first month. Patients who underwent hip surgery had, previously, cardiovascular diseases (75.9%). Death was associated with liver comorbidity in 13.3% and low weight in 33.3%. The fact of having two or more comorbidities was not associated with death. Conclusion: Liver and cardiovascular diseases and low weight are important prognostic predictors in mortality of patients over 61 years of age after femoral fracture surgery in the first month. (AU)

Linfoma NK/T extranodal diagnosticado como celulitis orbitaria refractaria a tratamiento

Varón de 60 años, con antecedente familiar de hermano fallecido con diagnóstico de linfoma de células Natural Killer/T extranodales (LNKTE) tipo nasal, presentó un cuadro clínico compatible con celulitis orbitaria izquierda y, posteriormente, deterioro del estado general e insuficiencia hepática. Sin adecuada respuesta a los antibióticos, la biopsia del párpado reveló un LNKTE. Recibió tratamiento con quimioterapia y falleció un mes después del diagnóstico.

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.