Insuficiencia hepática secundaria a enfermedad poliquística renal-hepática / Hepatic Failure Secondary to Polycystic Renal-Hepatic Disease

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(AU)

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(AU)

Diabetes Mellitus Y Su Manejo En Escenarios Difíciles / Diabetes mellitus and its management in difficult scenarios

Introducción: la diabetes mellitus se produce por la alteración en el metabolismo de los carbohidratos, su prevalencia viene en aumento debido al incremento en la tasa de obesidad y los cambios en los hábitos nutricionales. En Colombia, alrededor de 8,36 % de la población padece diabetes tipo 2 y menos del 1 % diabetes tipo 1. Metodología: se seleccionaron 51 artículos sobre diabetes y diferentes escenarios clínicos, publicados en su mayoría entre los años 2015-2021. Resultados: en los pacientes con enfermedad hepática crónica, se aumenta la resistencia a la insulina e intolerancia a la glucosa; por esto, deben ser tratados en primera instancia con metformina o insulinas. En los diabéticos el riesgo cardiovascular se incrementa tanto para infarto como para accidente cerebrovascular. En estos, se puede realizar tratamiento con metformina, empagliflozina, entre otros. Los pacientes con falla renal tienen mayor riesgo de hipoglicemia por el metabolismo prolongado de la insulina como consecuencia de la filtración glomerular, en estos son útiles medicamentos como liraglutide y sus similares. Conclusión: existen múltiples escenarios clínicos que se presentan en conjunto con la diabetes mellitus. Se deben tener en cuenta las múltiples comorbilidades de los pacientes al momento de instaurar un tratamiento y sus diferentes determinantes, para garantizar su efectividad.

Introduction: Diabetes mellitus is caused by alterations in carbohydrate metabolism and its prevalence is increasing due to the increase in the rate of obesity and changes in nutritional habits. In Colombia, about 8.36% of the population suffers from type 2 diabetes and less than 1% from type 1 diabetes. Methods: Fifty-one articles were selected, on diabetes and different clinical scenarios, mostly published between 2015-2021. Results: In patients with chronic liver disease, insulin resistance and glucose intolerance are increased; therefore, they should be treated in the first instance with Metformin or Insulin. In diabetics, cardiovascular risk is increased for both infarction and stroke. In these patients, treatment can be performed with Metformin, Empagliflozin, among others. Patients with renal failure have a higher risk of hypoglycemia due to prolonged insulin metabolism as a consequence of glomerular filtration; medications such as Liraglutide and similar drugs are useful in these patients. Conclusion: There are multiple clinical scenarios that occur in conjunction with diabetes mellitus. The multiple comorbidities of patients should be taken into account when instituting treatment and its different determinants to ensure the effectiveness of the treatment to be appropriate for the patients.

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

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

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

Diálisis de albúmina de paso único (SPAD) como soporte hepático extracorpóreo en paciente COVID-19 crítico. Caso clínico / Single-pass albumin dialysis as treatment of acute on chronic liver failure during COVID-19 pneumonia. report of one case

Liver transplantation is the only effective therapy to reduce the high mortality associated with acute liver failure and acute on chronic liver failure (ACLF). Single-pass albumin dialysis (SPAD) is an extracorporeal supportive therapy used as a bridge to liver transplantation or regeneration. We report a 44-year-old man with alcoholic cirrhosis admitted for critical COVID-19 pneumonia that evolves with ACLF. SPAD technique was performed completing six sessions, with a reduction of bilirubin and ammonia levels. He evolved with severe respiratory failure and refractory septic shock, dying. SPAD is a safe and efficient technique aimed to eliminate liver toxins, preventing multiorgan damage interrupting the process known as the "autointoxication hypothesis". It is easy to implement in any critical patient unit and has lower costs than other extracorporeal liver support therapies.

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.

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.

Evolución de los pacientes con enfermedad hepática crítica / Prognosis of patients with critical hepatic disease

INTRODUCTION: The acute liver failure on chronic (ACLF), is an entity, whose recognition is increasing. The ACLF and CLIF OF indexes have been recently presented with the objective of predicting mortality in this kind of patients. MATERIAL AND METHODS: All patients admitted to the Ramón y Cajal University Hospital diagnosed of acute liver failure on chronic during 2016 and 2017 were collected. We collect the scores: SOFA, CLIF, APACHE II, SAPS II and ACLF score in patients admitted to the ICU by comparing them with each other and define which stages have worse prognosis. RESULTS: A total of 46 patients were collected. The study presents an intra ICU mortality of 31% (15/46) and a six-month mortality of 59.6% (28/46). Patients classified as death, present ACLF values ​​at admission (49.5 vs 60 p = 0.001), and at three days (46.66 vs 59.4 p = 0.001) higher than survivors. In the analysis of the ROC curve, the area under the curve in relation to six-month mortality is higher in the ACLF index (0.8) compared to the MELD (0.69) SOFA (0.66) SAPS II (0.69) or APACHE II (0.65). Patients with ACLF indexes above 65 had an intra UCI mortality of 54%, however, mortality at 6 months is 90%. Patients with ACLF values ​​greater than 65 present mean values ​​of lactic acid, leukocytes, INR or bilirubin higher than those under 65 in a statistically significant manner. CONCLUSIONS: The data presented in this study suggest that the ACLF index works as an adequate predictor of intra-ICU mortality and at 6 months.

INTRODUCCIÓN: El fallo hepático agudo sobre crónico es una entidad cuyo reconocimiento va en aumento. Los índices ACLF y CLIF OF, han sido presentados recientemente con el objetivo de predecir la mortalidad en este tipo de enfermos. MATERIAL Y MÉTODOS: Se recogen todos los pacientes ingresados en una unidad de cuidados intensivos (UCI) de un hospital terciario universitario, diagnosticados de fallo hepático agudo sobre crónico durante 2016 y 2017. Recogemos los índices SOFA, CLIF, APACHE II, SAPS II Y ACLF en pacientes ingresados en UCI comparándolos entre sí. Definimos que estadios presentan peor pronóstico. RESULTADOS: Se analizan un total de 46 pacientes. El estudio presenta una mortalidad intra-UCI del 31% (15/46) y una mortalidad a los seis meses de 59,6% (28/46). Los pacientes clasificados como éxitus presentan valores ACLF al ingreso (49,5 vs 60 p = 0,001), a los tres días (46,66 vs 59,4 p = 0,001) superiores a los supervivientes. En el análisis de la curva COR, el área bajo la curva en relación a la mortalidad a los seis meses, es superior en el índice ACLF (0,8) en comparación con el MELD (0,69) SOFA (0,66) SAPS II (0,69) o APACHE II (0,65). Los pacientes con índices ACLF superiores a 65 presentaban una mortalidad intra-UCI del 54% sin embargo, la mortalidad a los 6 meses es del 90%. Los pacientes con valores ACLF superiores a 65 presentan a su vez valores medios de láctico, leucocitos, INR o bilirrubina mayores de forma estadísticamente significativa. CONCLUSIONES: Los datos presentados en este estudio sugieren que el índice ACLF funciona como un adecuado predictor de mortalidad intra-UCI y a los 6 meses.

Surgical management of large hepatocellular carcinoma: the first single-center study from western india / Manejo cirúrgico de grandes carcinomas hepatocelulares: primeiro estudo de um único centro da índia ocidental

ABSTRACT Background: Majority of patients with large size HCC (>10 cm) are not offered surgery as per Barcelona Clinic Liver Cancer (BCLC) criteria and hence, their outcomes are not well studied, especially from India, owing to a lower incidence. Aim: To analyze outcomes of surgery for large HCCs. Methods: This retrospective observational study included all patients who underwent surgery for large HCC from January 2007 to December 2017. The entire perioperative and follow up data was collected and analyzed. Results: Nineteen patients were included. Ten were non-cirrhotic; 16 were BCLC grade A; one BCLC grade B; and two were BCLC C. Two cirrhotic and three non-cirrhotic underwent preoperative sequential trans-arterial chemoembolization and portal vein embolization. Right hepatectomy was the most commonly done procedure. The postoperative 30-day mortality rate was 5% (1/19). Wound infection and postoperative ascites was seen in seven patients each. Postoperative liver failure was seen in five. Two cirrhotic and two non-cirrhotic patients had postoperative bile leak. The hospital stay was 11.9±5.4 days (median 12 days). Vascular invasion was present in four cirrhotic and five non-cirrhotic patients. The median follow-up was 32 months. Five patients died in the follow-up period. Seven had recurrence and median recurrence free survival was 18 months. The cumulative recurrence free survival was 88% and 54%, whereas the cumulative overall survival was 94% and 73% at one and three years respectively. Both were better in non-cirrhotic; however, the difference was not statistically significant. The recurrence free survival was better in patients without vascular invasion and the difference was statistically significant (p=0.011). Conclusion: Large HCC is not a contraindication for surgery. Vascular invasion if present, adversely affects survival. Proper case selection can provide the most favorable survival with minimal morbidity.

RESUMO Racional: A maioria dos pacientes com CHC de grande porte (>10 cm) não tem indicação cirúrgica conforme os critérios do Barcelona Clinic Liver Cancer (BCLC) e, portanto, seus resultados não são bem estudados, principalmente na Índia, devido a uma menor incidência. Objetivo: Analisar os resultados da cirurgia para HCCs de grande porte. Métodos: Este estudo observacional retrospectivo incluiu todos os pacientes submetidos à cirurgia para grandes CHC de janeiro de 2007 a dezembro de 2017. Todos os dados perioperatórios e de acompanhamento foram coletados e analisados. Resultados: Dezenove pacientes foram incluídos. Dez não eram cirróticos; 16 eram BCLC grau A; um BCLC grau B; e dois eram BCLC C. Dois cirróticos e três não-cirróticos foram submetidos à quimioembolização transarterial sequencial pré-operatória e embolização da veia porta. Hepatectomia direita foi o procedimento mais comumente realizado. A taxa de mortalidade pós-operatória em 30 dias foi de 5% (1/19). Infecção da ferida e ascite pós-operatória foram observadas em sete pacientes cada. Insuficiência hepática pós-operatória foi observada em cinco. Dois pacientes cirróticos e dois não cirróticos apresentaram vazamento de bile no pós-operatório. O tempo de internação foi de 11,9±5,4 dias (mediana de 12 dias). A invasão vascular estava presente em quatro pacientes cirróticos e cinco não cirróticos. O acompanhamento médio foi de 32 meses. Cinco pacientes morreram no período de acompanhamento. Sete tiveram recorrência e sobrevida mediana livre de recorrência foi de 18 meses. A sobrevida livre de recorrência cumulativa foi de 88% e 54%, enquanto a sobrevida global cumulativa foi de 94% e 73% em um e três anos, respectivamente. Ambos eram melhores em não-cirróticos; no entanto, a diferença não foi estatisticamente significante. A sobrevida livre de recidiva foi melhor nos pacientes sem invasão vascular e a diferença foi estatisticamente significante (p=0,011). Conclusão: CHC grande não é contraindicação para cirurgia. Invasão vascular, se presente, afeta adversamente a sobrevida. Seleção adequada de casos pode fornecer sobrevida mais favorável com morbidade mínima.

Lysosomal acid lipase deficiency in Brazilian children: a case series / Deficiência de lipase ácida lisossomal em crianças brasileiras: casuística

Abstract Objective: To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency. Methods: A retrospective review of the medical records of children with the disease. Results: Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3-10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms). Conclusion: This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.

Resumo: Objetivo: Descrever as características demográficas, clínicas, laboratoriais e moleculares de pacientes com deficiência de lipase ácida lisossomal. Métodos: Análise retrospectiva dos prontuários médicos de crianças com a deficiência de lipase ácida lisossomal. Resultados: Sete crianças com deficiência de lipase ácida lisossomal (5 M:2F); seis eram pardas e uma negra. As faixas etárias no início dos sintomas e no diagnóstico foram 5 anos (4 meses a 9 anos) e 6,9 anos (3 a 10 anos), respectivamente. As manifestações dos sintomas no início foram as que seguem: três pacientes apresentaram dor abdominal, um apresentou dor nos ossos/articulações devido a raquitismo e um apresentou diarreia crônica e insuficiência respiratória devido à pneumonite intersticial. Os outros não apresentaram sintomas e a suspeita clínica surgiu devido à hepatomegalia. Seis pacientes apresentaram hepatomegalia e um apresentou esplenomegalia. Dois pacientes eram irmãos. O ensaio enzimético e a análise molecular confirmaram os diagnósticos. A análise genética revelou uma variante patogênica rara (p.L89P) em três pacientes, descrita uma única vez na literatura médica e nunca descrita no Brasil. Nenhum desses pacientes tinha parentesco com os outros. A deficiência de lipase ácida lisossomal foi anteriormente descrita como uma doença recessiva autossômica, porém três pacientes eram heterozigotos e, sem dúvida, apresentaram a doença (atividade enzimática baixa, achados laboratoriais sugestivos e sintomas clínicos). Conclusão: Esta casuística afirma que a deficiência de lipase ácida lisossomal pode se manifestar com sinais e sintomas altamente heterogêneos entre os pacientes, porém deve ser considerada em crianças que apresentam sintomas gastrointestinais associados à dislipidemia. Descrevemos uma variante rara em três pacientes não relacionados que pode sugerir um genótipo brasileiro para deficiência de lipase ácida lisossomal.

Serum regucalcin is a useful indicator of liver injury severity in patients with hepatitis B virus-related liver diseases

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.

SOFA nas primeiras 24 horas como preditor de desfecho em insuficiência hepática aguda / SOFA in the first 24 hours as an outcome predictor of acute liver failure

RESUMO Objetivo: Descrever uma coorte de doentes com insuficiência hepática aguda, e analisar os fatores demográficos e clínicos associados à mortalidade. Métodos: Estudo de coorte retrospectivo em que todos os pacientes admitidos por insuficiência hepática aguda foram incluídos no período de 28 de julho de 2012 a 31 de agosto de 2017. Dados clínicos e demográficos foram coletados via Sistema Epimed. Foram mensurados SAPS 3, SOFA e MELD. Estimaram-se as OR e seus IC95%. Foram obtidas as curvas Características de Operação do Receptor para os escores de prognóstico, assim como a curva Kaplan-Meier de sobrevida para o escore com melhor predição de mortalidade. Resultados: A maioria dos 40 doentes era do sexo feminino (77,5%), e a etiologia mais frequente foi hepatite pelo vírus B (n = 13). Apenas 35% dos doentes foram submetidos ao transplante hepático. A mortalidade hospitalar foi de 57,5% (IC95%: 41,5 - 73,5). Dentre os escores investigados, apenas o SOFA se manteve associado ao risco de morte (OR = 1,37; IC95% 1,11 - 1,69; p < 0,001). Após a estratificação do SOFA em < 12 e ≥ 12 pontos, a sobrevida foi maior nos pacientes com SOFA < 12 (Log-rank p < 0,001). Conclusão: SOFA nas primeiras 24 horas foi o maior preditor de desfecho fatal.

ABSTRACT Objective: To describe a cohort of patients with acute liver failure and to analyze the demographic and clinical factors associated with mortality. Methods: Retrospective cohort study in which all patients admitted for acute liver failure from July 28, 2012, to August 31, 2017, were included. Clinical and demographic data were collected using the Epimed System. The SAPS 3, SOFA, and MELD scores were measured. The odds ratios and 95% confidence intervals were estimated. Receiver operating characteristics curves were obtained for the prognostic scores, along with the Kaplan-Meier survival curve for the score best predicting mortality. Results: The majority of the 40 patients were female (77.5%), and the most frequent etiology was hepatitis B (n = 13). Only 35% of the patients underwent liver transplantation. The in-hospital mortality rate was 57.5% (95%CI: 41.5 - 73.5). Among the scores investigated, only SOFA remained associated with risk of death (OR = 1.37; 95%CI 1.11 - 1.69; p < 0.001). After SOFA stratification into < 12 and ≥ 12 points, survival was higher in patients with SOFA <12 (log-rank p < 0.001). Conclusion: SOFA score in the first 24 hours was the best predictor of fatal outcome.

Falla hepática aguda sobre crónica (ACLF) ¿qué es, que sabemos y hacia dónde vamos? / Acute-on-chronic liver failure (ACLF) ¿what is it, what do we know about it and where are we going?

Acute on chronic liver failure (ACLF) is an increasingly recognized syndrome worldwide, in which there is great interest from different scientific societies and an increasing number of publications. It is defined as a syndrome of cirrhotic patients, characterized by the presence of acute decompensation, organ failure and high mortality rate in the short term. ACLF can be reversed using standard therapy in only 16-50% of patients, thus a prompt transfer to liver transplant center can make a difference in the survival chances of the patient.

La falla hepática aguda sobre crónica (ACLF, por su sigla en inglés) es un síndrome cada vez más reconocido a nivel mundial, que genera gran interés por parte de las distintas sociedades científicas y sobre el cual existe un número creciente de publicaciones. Se define como un síndrome de pacientes cirróticos, que se caracteriza por la presencia de una descompensación aguda, falla orgánica y elevada mortalidad a corto plazo. La reversibilidad de este síndrome con las medidas estándar es solo entre 16-50%, por lo que la derivación a un centro con disponibilidad de trasplante hepático puede hacer la diferencia en la sobrevida del paciente.

Prognostic factors of the short-term outcomes of patients with hepatitis B virus-associated acute-on-chronic liver failure

OBJECTIVE: To investigate the impact of the baseline status of patients with hepatitis B virus-associated acute-on-chronic liver failure on short-term outcomes. METHODS: A retrospective study was conducted that included a total of 138 patients with hepatitis B virus-associated acute-on-chronic liver failure admitted to the Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, from November 2013 to October 2016. The patients were divided into a poor prognosis group (74 patients) and a good prognosis group (64 patients) based on the disease outcome. General information, clinical indicators and prognostic scores of the patients' baseline status were analyzed, and a prediction model was established accordingly. RESULTS: Elder age, treatment with artificial liver support systems and the frequency of such treatments, high levels of white blood cells, neutrophils, neutrophil count/lymphocyte count ratio, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, urea, and prognostic scores as well as low levels of albumin and sodium were all significantly associated with the short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure. The predictive model showed that logit (p) = 3.068 + 1.003 × neutrophil count/lymphocyte count ratio - 0.892 × gamma-glutamyl transferase - 1.138 × albumin - 1.364 × sodium + 1.651 × artificial liver support therapy. CONCLUSION: The neutrophil count/lymphocyte count ratio and serum levels of gamma-glutamyl transferase, albumin and sodium were independent risk factors predicting short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure, and the administration of multiple treatments with artificial liver support therapy during the early stage is conducive to improved short-term outcomes.

Síndrome inflamatória de reconstituição imune como causa de hepatite autoimune e insuficiência hepática aguda / Immune reconstitution inflammatory syndrome as a cause of autoimmune hepatitis and acute liver failure

RESUMO A insuficiência hepática aguda é uma síndrome rara com elevada mortalidade e frequentemente reconhecida de forma tardia. Os médicos intensivistas desempenham um papel fundamental na suspeição diagnóstica e no manejo das disfunções múltiplo-orgânicas características desta entidade. A síndrome inflamatória de reconstituição imune é uma entidade que se caracteriza pela piora paradoxal do quadro prévio do paciente, após o início de antirretrovirais, desencadeada contra patógenos presentes no hospedeiro ou autoantígenos. A hepatite autoimune tem sido recentemente descrita como uma destas manifestações autoimunes. Os autores relatam o primeiro caso com evolução à insuficiência hepática aguda e óbito em poucos dias após o desenvolvimento de encefalopatia, revisam os casos de hepatite autoimune descritos e tecem comentários sobre as possibilidades terapêuticas neste contexto.

ABSTRACT Acute liver failure is a rare syndrome with high mortality and is often diagnosed late. Intensivist physicians play fundamental roles in the diagnostic suspicion and the management of the multiple-organic dysfunctions characteristic of this entity. Immune reconstitution inflammatory syndrome is an entity that is characterized by the paradoxical worsening of the patient's previous condition, after the initiation of antiretrovirals, triggered against either pathogens present in the host or autoantigens. Autoimmune hepatitis has recently been described as one of these autoimmune manifestations. The authors report the first case with evolution to acute liver failure and death within a few days after the development of encephalopathy, review the cases of autoimmune hepatitis described and comment on the therapeutic possibilities in this context.

Utility and Safety of Tolvaptan in Cirrhotic Patients with Hyponatremia: a Prospective Cohort Study

Abstract: Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free wáter excretion, but its efficacy and safety in cirrhotic patients remain unclear. Material and methods. We studied the usage and safety of tolvaptan in cirrhotic patients in a real-life, non-randomized, multicenter prospective cohort study. Forty-nine cirrhotic patients with hyponatremia were treated with tolvaptan 15 mg daily, and 48 patients not treated with tolvaptan in the same period served as controls. Improvement in serum sodium level was defined as an increase in serum sodium from < 125 to ≥ 125 mmol/L or from 125-134 to ≥ 135 mmol/L on day 7. Results. Twenty-three (47%) patients in the tolvaptan group and 17 (35%) in the control group had normal serum sodium on day 7 (p = 0.25). Serum sodium improved in 30 (61%) patients in the tolvaptan group and 17 (35%) patients in the control group (p = 0.011). Adverse events occurred in 46-47% of patients in both groups, and tolvaptan was not associated with worsened liver function. No patient with normal serum sodium on day 7 died within 30 days of treatment, whereas 16% of those with persistent hyponatremia died (p = 0.0019). Conclusion. In conclusion, short-term tolvaptan treatment is safe and can improve serum sodium level in cirrhotic patients with hyponatremia. Normalization of serum sodium level is associated with better survival.

Estudo de gene da lectina ligadora de manose em doador falecido e transplante de fígado - relato de caso / Gene study of mannose-binding lectin in deceased donor and liver transplantation - case report

A hepatite autoimune é uma doença de curso crônico e etiologia ainda não esclarecida, que em alguns casos evolui para falência hepática aguda, condição em que o tratamento definitivo é o transplante hepático. Assumidos todos os riscos da cirurgia, restam ainda outras variáveis que concorrem para o êxito do tratamento, como a influência do sistema imune. Dentre essas, uma alteração na formação da lectina ligadora de manose (MBL), presente no fígado do doador, está relacionada a uma maior predisposição do receptor a eventos infecciosos. Relata-se o caso de uma paciente de 18 anos, submetida ao transplante hepático por falência hepática aguda, que, no pós-operatório, apresentou choque séptico de origem desconhecida, evoluindo a óbito. O doador foi genotipado com polimorfismo da MBL relacionado a níveis intermediários ou baixos de MBL sérica. Complicações infecciosas pós-transplantes continuam sendo frequentes nos receptores de órgãos. Assim, a utilização de parâmetros modificadores de resposta imune, como a MBL, poderá ajudar a melhorar o prognóstico desses pacientes.

Autoimmune hepatitisis mostly a chronic disease, which etiology remains unclear, progressing in some cases to acute liver failure, a condition whose definitive treatmentis liver transplantation. Assume dallrisks of surgery, there are still other variables that contribute to the success of the treatment, as the influence of the immune system. Among these, a change in the formation of mannose bindin glectin (MBL), present in the do nor liver, is related to increased predisposition to infectious events in the receptor. It is reported a case of a 18 year old patient who under went liver transplantation for acute liver failure, which evolved post operatively to septics hockofunk now no riginand death. The liver donor was genotyped with polymorphis mof MBL, related to intermediate or low level sof sérum MBL. Post-operative infectious complications remain common in organ recipients. Thus, the use of modified parameters in immune response, such as MBL, may help to improve the prognosis of these patients.

Falência hepática aguda em crianças e adolescentes / Acute liver failure in children and adolescents

A halência hepática aguda (FHA) é uma condição rara, mas devastadora, que evolui para falência de múltiplos órgãos e óbito como seu curso natural. A assistência intensiva e o transplante hepático possibilitaram a modificação da história natural e aumento da sobrevida. A FHA, geralmente, se apresenta em uma criança ou adolescente previamente hígido que inicia com sintomas inespecíficos de duração variada e com a evolução do quadro surgem outros sintomas como icterícia, vômitos, hipoglicemia e convulsões, tornando a síndrome clínica evidente. O diagnóstico etiológico é importante, uma vez que algumas doenças de base possuem tratamentos específicos. Contudo, em até 50% dos casos, um diagnóstico específico não é estabelecido. Sua presença será estabelecida se há evidência bioquímica de falência hepática aguda, na ausência de doença hepática crônica e associada à coagulopatia de origem hepática não corrigível pela vitamina K (RNI > 1,5 em paciente com encefalopatia hepática ou RNI ? 2 na ausência de encefalopatia hepática). O tempo entre o início do quadro clínico e o desenvolvimento da encefalopatia deve ser inferior a oito semanas. O reconhecimento e o encaminhamento para centro especializado devem ser o mais precoce possível. A indicação de transplante hepático deve ser avaliada periodicamente. O tratamento intensivo e multidisciplinar é essencial para sobrevida.

The Acute Liver Failure (ALF) is a rare but devastating condition that can lead to multiple organ failure and death as its natural course. Intensive therapy and liver transplantation have changed its natural history and raised survival rates. ALF usually presents in a previously healthy child who initiates with unspecific symptoms of variable duration and then evolve with jaundice, vomiting, hypoglycemia and seizures, when the clinical syndrome becomes evident. The etiologic diagnosis is importantbecause some diseases have specific treatments. However in 50% of the cases a specific diagnosis is not estabilished. The criteria for diagnosing ALF is biochemical evidence of acute hepatic failure without signs of chronic liver disease associated with coagulopathy non responsive to vitamin K (INR>1,5 with encephalopathy or INR>2 regardless the presence of encephalopathy signs). The time between the initial symptoms and the development of encephalopathy must be less than 8 weeks. Recognizing and referring the patient for a reference center must be a priority. The need for liver transplantation should be periodically assessed. Intensive multidisciplinary care is essential for survival.

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)