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.

Liver transplantation for acute liver failure due to antitubercular drugs - a single-center experience

OBJECTIVES: Patients receiving treatment for tuberculosis are at risk of developing acute liver failure due to the hepatotoxicity of antitubercular drugs. We aimed to describe our experience with liver transplantation from deceased donors in this situation. METHODS: We identified patients undergoing transplantation for acute liver failure due to antitubercular drugs in our prospectively maintained database. RESULTS: Of 81 patients undergoing transplantation for acute liver failure, 8 cases were attributed to antitubercular drugs during the period of 2006-2016. Regarding the time of tuberculosis treatment until the onset of jaundice, patients were on antitubercular drugs for a mean of 64.7 days (21-155 days). The model for end-stage liver disease (MELD) score of patients ranged from 32 to 47 (median 38), and seven patients underwent transplantation under vasopressors. The 1-year survival was 50%. Three patients died during the week following transplantation due to septic shock (including a patient with acute liver failure due to hepatic/disseminated tuberculosis), and the remaining patient died 2 months after transplantation due to pulmonary infection. There were 2 cases of mild rejection and 1 case of moderate rejection. Of the surviving patients, all were considered cured of tuberculosis after alternative drugs were given. CONCLUSION: Patients arrived very sick and displayed poor survival after deceased donor transplantation.

A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in 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.

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

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

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

Falla hepática fulminante en niños / Acute liver failure in children: experience of a liver transplant center

Background: Acute liver failure (ALF) in childhood is defined as biochemical evidence of liver injury, absence of known chronic liver disease and coagulopathy not corrected by vitamin K administration, with INR greater than 1.5 if the patient has encephalopathy or greater than 2.0 if the patient does not have encephalopathy. Objective: Report the experience of a single liver transplant center (LT) in the treatment of 8 children with ALF and review the literature. Method: Retrospective review of clinical charts of patients with ALF. Results: The median age was 8 years-old (range 0-11), three females. Five patients underwent LT. Two patients died, one of them LT. The etiologies were 4 undetermined, 1 autoimmune, 1 Wilson Disease, 1 Parvo virus and 1 chronic graft rejection. All grafts were from cadaver donor, 3 of them reduced. Two out of five patients with encephalopathy grade III-IV died. The one year survival rate was 75 percent. Conclusions: Children with ALF should be treated in experienced centers with facilities for liver transplant. Transplantation should be offered only if the underlying disease is treatable by liver replacement and if transplant prognosis is better than that of the underlying disease.

Falla hepática fulminante (FHF) en la infancia se define como evidencia bioquímica de daño hepático, sin antecedentes conocidos de enfermedad hepática crónica, coagulopatía no corregida por la administración de vitamina K e INR superior a 1,5 si el paciente tiene encefalopatía o superior a 2 si no tiene encefalopatía. Objetivo: Presentar la experiencia de un centro de trasplante hepático (TH) en el tratamiento de 8 niños con FHF y revisar la literatura. Pacientes y Método: Revisión retrospectiva de la historia clínica de pacientes con FHF. Resultados: La edad media fue de 8 años, rango 0-11, tres sexo femenino. Cinco pacientes fueron sometidos a TH. Dos pacientes fallecieron, uno de ellos con TH. La etiología fue indeterminada en 4 pacientes, 1 autoinmune, 1 enfermedad de Wilson, 1 parvovirus y 1 rechazo crónico del injerto. Todos los injertos fueron de donante cadáver, 3 de ellos reducidos. Dos de cinco pacientes con encefalopatía grado III-IV fallecieron. La tasa de sobrevida al año fue de 75 por ciento. Conclusión: El manejo de la FHF debe realizarse en un centro con capacidad de realizar TH, aunque no todos los pacientes requerirán finalmente esta terapia. El TH debiera ser ofrecido sólo si la enfermedad subyacente es tratable con reemplazo hepático y si el pronóstico del TH es mejor que el de la enfermedad misma.

Liver transplantation for acute liver failure: a 5 years experience / Transplante hepático na hepatite fulminante: uma experiência de 5 anos

BACKGROUND: Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. AIM: To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. METHODS: A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease) scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. RESULTS: Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2 percent at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. CONCLUSION: Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients.

RACIONAL: OBJETIVO: Avaliar a evolução de 20 pacientes com insuficiência hepática aguda e indicação de transplante hepático. MÉTODOS: Foi realizado estudo retrospectivo de 20 pacientes com insuficiência hepática aguda e indicação de transplante hepático. Os pacientes foram divididos em dois grupos: grupo A com 12 pacientes que foram submetidos a transplante hepático e grupo B com oito pacientes não submetidos a transplante hepático. Ambos os grupos foram analisados de acordo com idade, sexo, tipagem sangüínea, etiologia da insuficiência hepática aguda, tempo em lista até o transplante ou até o óbito e sobrevida. Os pacientes do grupo A foram ainda analisados de acordo com o escore MELD (Model for End-stage Liver Disease), valores de pico pré-operatório de INR, AST e ALT, necessidade de transfusão de concentrado de hemácias e plasma fresco congelado durante o transplante, tempo de isquemia fria, tempo de permanência hospitalar e em unidade de terapia intensiva e necessidade de diálise no pós-transplante imediato. RESULTADOS: Grupo A: o tempo médio de espera em lista até o transplante foi de 3,4 dias e o MELD médio, de 36. Sete pacientes continuam vivos com boa função hepática em um tempo médio de seguimento de 26,2 meses. A sobrevida atuarial em 1 ano foi de 65,2 por cento. Grupo B: foram estudados dois homens e seis mulheres com média de idade de 30,9 anos. O tempo médio de espera em lista até o óbito foi de 7,4 dias. Todos os pacientes foram a óbito esperando por um doador. CONCLUSÃO: Mesmo com todos os avanços nos cuidados de terapia intensiva, a maioria dos pacientes com insuficiência hepática aguda e indicação de transplante hepático não sobrevivem por muito tempo sem o transplante. O transplante hepático é potencialmente a única terapêutica curativa atualmente disponível e melhorou consideravelmente o prognóstico desses pacientes.

Factores pronósticos en insuficiencia hepática aguda / Prognoses factors in acute hepatic insufficiency

Introducción. La insuficiencia hepática aguda (IHA) es un síndrome poco frecuente aunque con elevada mortalidad. El objetivo de este estudio fue determinar las características clínico-epidemiológicas de la IHA. Materiales y métodos: Estudio abierto, prospectivo, descriptivo de pacientes con diagnóstico de IHA hospitalizados en la Unidad de Hígado del HNERM desde Febrero 1999 hasta Enero 2003. Resultados. Se estudiaron 15 casos. La edad promedio fue 63 años (30-81), la relación M/F fue 2/1. La etiología fue hepatitis viral B (53.3 por ciento), reacciones tóxicas por idiosincracia (20 por ciento), indeterminada (20 por ciento) y hepatitis A (6.7 por ciento). En el momento del diagnóstico el 80 por ciento presentó encefalopatía Grado I y el 20 por ciento encefalopatía III. El 13.3 por ciento no tuvo ascitis y el 86.7 por ciento ascitis leve-moderada. El 53.3 por ciento tenía como antecedente una enfermedad crónica (diabetes, insuficiencia renal crónica, cardiopatía y otros). Los valores de laboratorio fueron: albúmina media 2.5 gr./dl, bilirrubina media 25.9 mg/dl, tiempo de protrombina media 29'' y Factor V media 40.7 por ciento. Las complicaciones más frecuentes fueron la sepsis y el edema cerebral. La mortalidad global fue 80 por ciento. El tiempo de sobrevida media fue 16.6 días. Conclusiones. La mayoría de casos tuvieron más de 60 años. La principal causa de IHA fue la hepatitis viral B, esta enfermedad puede prevenirse con la inmunización activa. La infección y el edema cerebral fueron causas importantes de muerte. La IHA aunque rara, es una entidad rápidamente progresiva y fatal.

Introduction. Acute Hepatic Insufficiency (AHI) is a rare syndrome but has a highmortality rate. The purpose of this study was to determine the clinico-epidemiological characteristics of AHI. Materials and Methods. Open study, prospective, descriptive of patients diagnosed with AHI in the Liver Unit of the Edgardo Rebagliati Martins State Hospital (HNERM) from February 1999 until January 2003. Results. Fifteen (15) cases were studied. The average age was 63 (30-81), the M-Fratio was 2/1. The diagnosis was viral Hepatitis B (53.3 per cent), toxic idiosyncratic reactions(20 per cent), undetermined (20 per cent) and Hepatitis A (6.7 per cent). At the time of diagnosis 80 per cent had Grade I encephalopathyand 20 per cent Grade III encephalopathy; 13.3 per cent did not have ascites and 86.7 per cent had mild-moderate ascites; 53.3 per cent had a history of chronic illness (diabetes, chronic renal insufficiency, cardiopathy and others). Average laboratory values were: albumin 2.5 gr./dl, bilirubin 25.9 mg/dl, prothrombin time 29” and Factor V 40.7 per cent. The most frequent complications were sepsis and cerebral oedema. Global mortality was 80 per cent. The average survival time was 16.6 days.Conclusions. In most cases the patients were over 60 years of age. The main cause of AHI was viral Hepatitis B, a disease which can be prevented with active immunisation. Infection and cerebral oedema were common causes of death. AHI, although rare, is a rapidly degenerative and fatal condition.

Outcome of acute liver failure due to acute hepatitis E in pregnant women.

INTRODUCTION: Acute liver failure due to acute hepatitis E carries a high mortality. METHODS: Clinical and laboratory parameters of 42 pregnant women (median age 25.5 years) with acute liver failure due to acute hepatitis E were retrospectively analyzed. RESULTS: 22 women delivered, whereas pregnancy continued in 20 women. The maternal mortality in these two groups was similar (9/22 [41%] versus 14/20 [70%], p=0.056). However, in patients with grade I, II or III hepatic encephalopathy, delivery of fetus was associated with reduced mortality in those who delivered as against those who continued pregnancy (5/16 (31%) vs. 13/20 (65%), p=0.046). On multivariate analysis, higher grade of encephalopathy at admission was associated with risk of death (p=0.005). CONCLUSION: Mortality in pregnant women with acute liver failure with acute hepatitis E is high, especially in patients who present with higher grades of encephalopathy.

Disfunción hepática en el trasplante de celulas progenitoras hematopoyéticas: Impacto sobre la mortalidad / Liver dysfunction in recipients of hematopoietic stem cells: Impact on mortality

El compromiso hepático en receptores de transplante alogénico de células progenitoras hemotopoyéticas (TCPH) es una complicación muy frecuente y es responsable de la morbimortalidad precoz. La toxicidad por fármacos la enfermedad injerto versus huésped ( EICH) , la enfermedad venooclusiva (EVO) y las infecciones fúngicas, bacterianas y virales constituyen las principales etiologias. El objetivo de este estúdio retrospectivo fue estabelecer la prevalencia y etiología de la afectación hepática, evaluar el impacto en la mortalidad y analizar el valor predictivo de las transaminasas pré TCPH en la ocurrencia de EICH agudo, crônico y mortalidad. De un total de 236 pacientes transplantados, se evaluaron 82 sometidos a TCPH alogénico. El 88% de los pacientes tuvo afectación hepática: EICH agudo 40.2%, EICH crônico 15.9%, de causa indeterminada 9.8% sepsis 7.3%, toxicidad por fármacos 6.1%, EVO 3.7%, hepatitis aguda y recidiva de enfermedad 2.4%. La mortalidad evaluada al año fue 36.6%. La insuficiência hepática aguda (IHA) represento el 10% de las muertes. Las causas de IHA fueron: progresón de EICH agudo, recidiva de la enfermedad hematológica en el hígado, hepatitis herpética y EVO. El valor predictivo positivo de las transaminasas pré TCPH para EICH agudo, crônico y mortalidad fue 0.27, 0.14 y 0.43 respectivamente. No se hallaron diferencias significativas entre pacientes con pruebas bioquímicas hepáticas pré TCPH alteradas o normales en la ocurrencia de EICH agudo, crónico o mortalidad.

Acute liver failure: prognostic markers.

Acute liver failure (ALF) is defined as liver failure occurring within one month of the occurrence of jaundice. The disease has a grim prognosis, with a mortality of 65% to 85%. The management of ALF has till recently been conservative, and newer therapeutic modalities like bioartificial liver, hepatocyte transplant, and extracorporeal liver assist devices have not yet been proven to be successful. Liver transplant has changed the gloomy outlook of the disease, and post-transplant survival rates of 60%-70% have been reported from most centers. However liver transplant is expensive, necessitates life-long immunosupression, and is limited by a global shortage of available organs. It is thus necessary to select patients who are at greatest risk of death for liver transplantation. Prognostic criteria are based primarily either on clinical and laboratory (coagulation tests, serum bilirubin) parameters, or on other parameters like liver volume. Prognostic criteria have been developed both from the East and the West; these are essentially similar except that the Western criteria take into account etiology (drug overdose being the main cause of ALF there) as well as jaundice-encephalopathy interval as factors for prognostication. The King's College criteria were one of the first prognostic systems; it has two parts for both paracetamol as well as non paracetamol ALF. The criteria from our institute found prothrombin time >25 s, serum bilirubin >15 mg/dL, age >40 years, and cerebral edema to be bad prognostic markers. Criteria from the PGIMER, Chandigarh found age >50 years, raised intracranial pressure, prothrombin time >100 s, and onset of HE more than seven days after the jaundice as poor prognostic markers. All these clinical criteria have similar sensitivity and specificity.

Acute liver failure.

Acute liver failure in children is associated with a high mortality. Most cases in our setup are due to water borne hepatotropic viruses HAV and HEV. The clinician must be aware of the earliest and the subtle signs of acute liver failure to identify cases early enough and institute supportive therapy. Focus of therapy has to be on prevention, early recognition and appropriate management of complications. Despite good intensive care, about 40-60% children with liver failure die. As and when liver transplantation becomes available in India, it would be an attractive option.

Acute liver failure in children: observations in Vitória, Espírito Santo State, Brazil

In this communication we report 46 cases of acute liver failure in children diagnosed at the Hospital Infantil Nossa Senhora da Glória in Vitória, E Santo. Serology for IgM anti-HAV, IgM anti-HBc, HbsAg, anti-HCV and biochemical tests were performed in all cases in a routine laboratory. The M/F ratio was 1.1:1 and the mean age was 4.7±3.2 years, without gender difference. Anti-HAV IgM+ in 38 (82.6 percent) cases, anti-HbcIgM+ in two (4.3 percent) cases and 6 (13.1 percent) cases were negative for all viral markers investigated. Anti- HCV+ in one anti-HAV IgM+ case. HbsAg+ in two anti-HbcIgM+ and in two HAVIgM+ cases. Among the six A, B and C negative cases, four (8.6 percent) did not have the suspected exogenous intoxication. Mortality was 50 percent, without gender or age differences. These results demonstrate that HAV infection is the main etiology of acute liver failure in children in Brazil, confirming that, although it is a self limited, relatively mild illness, it can cause serious and even fatal disease. The observation of four cases without A, B and C viral markers and no history of exogenous intoxication, agree with the observation of non A-E acute sporadic hepatitis in Northeastern Brazil

Liver transplantation in the developing world.

Liver transplantation is an accepted therapy for acute and chronic liver failure. Advances in preoperative and postoperative management and surgical techniques have extended the indications and improved results. Most international centres report one year actual survival rates of between 58-90% and 5-8 years survival of 75-80%. These developments, however, have been limited largely to the West. While the need for liver transplantation is well recognised in the developing world, liver transplantation has only recently been performed successfully in India. This article examines the challenges of liver transplantation in the developing world.