Acute liver failure caused by lymphocyte-depleted Hodgkin lymphoma in tuberculosis and HIV-infected patient.

The lymphocyte-depleted classic Hodgkin lymphoma (LDCHL), the rarest subtype of classic Hodgkin lymphoma (CHL), is usually diagnosed at an advanced stage (stage IV) and one that unusually involves the liver, causing a rapidly progressive clinical course. We describe a 40-year-old immunocompromised man presenting with a progressive non-cholestatic jaundice and intermittent fever. The abdominal ultrasonography revealed a nodular liver with coarse echotexture and periportal hypodensities. The thoracic and abdominal contrast-enhanced computed tomography revealed right cervical and paraaortic lymphadenopathy, hepatosplenomegaly, diffuse mural thickening of duodenal and jejunal loops, and bilateral lobulated kidneys. Subsequently, he succumbed to his illness secondary to refractory septic shock. On postmortem examination, he was diagnosed with classic Hodgkin lymphoma (lymphocyte-depleted type) involving paraaortic and mediastinal lymph nodes based on morphology and immunochemistry findings. The lymphomatous process involved the liver (causing multiacinar confluent hepatic necrosis) and spleen, both showing tuberculous foci. This autopsy case depicts an uncommon case of acute liver failure due to infiltration of the liver by LDCHL in an HIV-infected patient. The findings of angiotropism and angioinvasion establish the pathological mechanism of liver failure (hepatocellular necrosis) in such cases.

Acute liver failure caused by lymphocyte-depleted Hodgkin lymphoma in tuberculosis and HIV-infected patient

ABSTRACT The lymphocyte-depleted classic Hodgkin lymphoma (LDCHL), the rarest subtype of classic Hodgkin lymphoma (CHL), is usually diagnosed at an advanced stage (stage IV) and one that unusually involves the liver, causing a rapidly progressive clinical course. We describe a 40-year-old immunocompromised man presenting with a progressive non-cholestatic jaundice and intermittent fever. The abdominal ultrasonography revealed a nodular liver with coarse echotexture and periportal hypodensities. The thoracic and abdominal contrast-enhanced computed tomography revealed right cervical and paraaortic lymphadenopathy, hepatosplenomegaly, diffuse mural thickening of duodenal and jejunal loops, and bilateral lobulated kidneys. Subsequently, he succumbed to his illness secondary to refractory septic shock. On postmortem examination, he was diagnosed with classic Hodgkin lymphoma (lymphocyte-depleted type) involving paraaortic and mediastinal lymph nodes based on morphology and immunochemistry findings. The lymphomatous process involved the liver (causing multiacinar confluent hepatic necrosis) and spleen, both showing tuberculous foci. This autopsy case depicts an uncommon case of acute liver failure due to infiltration of the liver by LDCHL in an HIV-infected patient. The findings of angiotropism and angioinvasion establish the pathological mechanism of liver failure (hepatocellular necrosis) in such cases.

Prognostic factors of liver transplantation for acute-on-chronic liver failure / Fatores prognósticos de transplante hepático em "acute-on-chronic liver failure"

ABSTRACT BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

RESUMO RACIONAL: O transplante hepático (TH) é o único tratamento a proporcionar sobrevida a longo prazo para pacientes com "acute-on-chronic liver failure" (ACLF). Vários estudos identificaram fatores prognósticos para pacientes em ACLF que não realizam TH, porém há poucos dados na literatura sobre fatores prognósticos nessa população transplantada. OBJETIVOS: Avaliar desfechos de pacientes ACLF submetidos a TH, e seus preditores de mortalidade. MÉTODOS: Foram avaliados pacientes em ACLF submetidos a TH entre janeiro de 2005 e abril de 2021. Variáveis como valores CLIF-C ACLF e pontuação no ACLF foram comparadas com os desfechos. RESULTADOS: A sobrevida de ACLF pós TH de pacientes (n=25) em 90 dias, 1, 3, 5 e 7 anos, foi de 80, 76, 59,5, 54,1 e 54,1% versus 86,3, 79,4, 72,6, 66,5 e 61,2% para pacientes submetidos a TH por outras indicações (n=344), (p=0,525). Não houve diferença estatística para mortalidade em 01 ano e 90 dias entre pacientes com os três graus de ACLF (ACLF-1 vs. ACLF-2 vs. ACLF-3), bem como quando comparados a pacientes não ACLF. O escore "chronic liver failure consortium" (CLIF-C) ACLF não se correlacionou com desfechos de óbito. Nenhuma das outras variáveis estudadas mostrou-se preditora independente de mortalidade em 90 dias, após um ano ou global. CONCLUSÕES: TH conferiu sobrevida em longo prazo à maioria dos pacientes transplantados, semelhante aos pacientes submetidos à TH por outras indicações. Nenhuma das variáveis estudadas mostrou-se fator prognóstico associado a desfechos de sobrevida pós-TH para pacientes com ACLF. Estudos adicionais são necessários para estabelecer fatores prognósticos pós-TH em pacientes com ACLF.

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.

Adverse reactions to antituberculosis drugs presenting as DRESS syndrome and acute liver failure

Drug induced liver injury (DILI) can be can be triggered by many medications including antituberculosis drugs. We present the case of a 37-year-old woman with a smear- positive pulmonary tuberculosis who started treatment with first-line antituberculosis drugs and 4 weeks later presented jaundice, somnolence and a morbilliform generalized rash with progressive neurologic deterioration which had a fatal outcome. Antituberculosis drugs can cause DILI in 2 to 28% of patients and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) in 1.2%. Acute liver failure (ALF) can occur in 35% of patients with DILI with an overall mortality of 9.7%. If the ALF is unresponsive to medical treatment, liver transplantation has shown promising results and can avoid progression of complications. DILI can be a serious medical condition in patients receiving antituberculosis drugs. If ALF develops and is unresponsive to medical treatment, liver transplantation should be considered as the treatment of choice.

La injuria hepática inducida por fármacos (IHIF) puede ser desencadenado por varios medicamentos incluyendo fármacos anti tuberculosos. Presentamos el caso de una paciente mujer de 37 años con un frotis positivo para tuberculosis pulmonar quien inició tratamiento de primera línea y 4 semanas después, presentó ictericia, somnolencia y un exantema generalizado de tipo morbiliforme con deterioro neurológico progresivo y un desenlace fatal. Los fármacos anti tuberculosos pueden producir injuria inducida por fármacos en 2 a 28% de pacientes y síndrome de DRESS (reacción de sensibilidad a medicamentos con eosinofilia y síntomas sistémicos) en 1,2%. La falla hepática aguda (FHA) en pacientes con injuria hepática inducida por fármacos, puede presentarse en un 35% con una mortalidad del 9,7%. Si la FHA no responde a tratamiento médico, el trasplante hepático ha mostrado resultados positivos y evita la progresión de complicaciones. La IHIF puede ser una condición médica grave en pacientes que reciben medicamentos antituberculosos. Si se desencadena una FHA y no responde a tratamiento médico, debe considerarse con urgencia la posibilidad de trasplante hepático.

N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury: a systematic review and meta-analysis.

The role of N-acetylcysteine (NAC) in the treatment of acetaminophen induced acute liver injury (ALI) is well established but its role in non-acetaminophen induced ALI is still elusive. We conducted this meta-analysis to evaluate the role of NAC in non-acetaminophen induced ALI. We searched electronic databases for studies published till Oct 25, 2020. We used RevMan v5.4 software to analyze the data extracted from selected studies by using Covidence systematic review software. Outcome estimation was done using Odds Ratio (OR) with 95% confidence interval (CI). The heterogeneity in various studies was determined using the I2 test. A total of 11 studies were included in quantitative analysis. Use of NAC in non-acetaminophen induced ALI showed 53% reduction in mortality compared to standard of care (OR, 0.47; CI, 0.29-0.75) and reduced mean duration of hospital stay by 6.52 days (95% CI, -12.91 to -0.13). Similarly, the rate of encephalopathy was 59% lower in the treatment group (OR, 0.41; CI, 0.20-0.83). However, the risk of developing nausea and vomiting (OR, 3.99; CI, 1.42-11.19), and the need for mechanical ventilation (OR 3.88; CI, 1.14-13.29) were significantly higher in the treatment group. These findings conclude use of NAC decreases mortality and hepatic encephalopathy compared to standard of care in patients with non-acetaminophen induced ALI. Although there is an increased risk of nausea and vomiting with the use of NAC, the majority of adverse events are transient and minor.

Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH) / Liver transplantation in a patient with human immunodeficiency virus (HIV): case report

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

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

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

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

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.

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

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

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

Nimesulide-induced fatal acute liver failure in an elderly woman with metastatic biliary adenocarcinoma. A case report / Insuficiência hepática aguda fatal induzida por nimesulida em uma mulher idosa com adenocarcinoma biliar metastático. Um relato de caso

CONTEXT:Nimesulide is a selective inhibitor of the enzyme cyclooxygenase 2. Although considered to be a safe drug, cases of acute hepatitis and fulminant liver failure have been reported in Europe, the United States and South America, especially among elderly female patients. Until now, there had not been any reports in the literature relating to Brazilian subjects.CASE REPORT:An 81-year old female who had been using nimesulide therapy for six days presented hematemesis and epistaxis two days before hospitalization. Clinical examination showed an extensive coagulation disorder, diffuse hematomas, hypotension and tachypnea. Laboratory tests revealed abnormalities in coagulation tests; leukocytosis; reduced platelet, hemoglobin and red blood cell counts; and elevated direct bilirubin, serum aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase and renal function biomarkers. Hepatitis B and C tests were not reactive. Carcinoembryonic antigen (CEA), CA-19-9 and CA-125 levels were increased by, respectively, 1,000, 10,000 and 13 fold, whereas the alpha-fetoprotein level was normal, thus indicating a malignant tumor in the bile duct that did not originate from the liver. Thirty-six hours after hospitalization, the patient's condition worsened, leading to death. The necropsy findings included acute hepatitis with hepatocellular collapse, as well as metastasis of a carcinoma, probably from the bile duct.CONCLUSION:Despite the carcinoma presented by the patient, nimesulide use may have contributed towards the fatal acute liver failure. Until this issue has been clarified, caution is required in prescribing nimesulide for liver disease patients.

CONTEXTO:A nimesulida é um inibidor seletivo da enzima ciclo-oxigenase 2. Apesar de ela ser considerada fármaco seguro, casos de hepatite aguda e falência hepática fulminante foram descritos na Europa, Estados Unidos e América do Sul, principalmente em idosos do sexo feminino. Até o momento não há relatos na literatura em indivíduos brasileiros.RELATO DE CASO:Mulher de 81 anos, em uso terapêutico de nimesulida por seis dias, apresentou hematêmese e epistaxe dois dias antes da hospitalização. O exame clínico mostrou importante distúrbio de coagulação, hematomas difusos, hipotensão e taquipneia. Os exames laboratoriais mostravam alteração das provas de coagulação, leucocitose, redução do número de plaquetas, hemoglobina e hemácias, aumento de bilirrubina direta, elevação dos valores de aspartato aminotransferase (AST), gama glutamil transpeptidase (GGT), fosfatase alcalina e marcadores de função renal. Exames para hepatite B e C apresentaram-se não reagentes. Elevados níveis dos marcadores antígeno carcinoembriônico (CEA), CA-19-9 e CA-125 foram encontrados (1.000, 10.000 e 13 vezes, respectivamente), enquanto a alfa-fetoproteína estava normal, indicando um tumor maligno no ducto biliar, não oriundo do fígado. Trinta e seis horas após a hospitalização, a paciente evoluiu a óbito. Os achados necroscópicos incluíram hepatite aguda com colapso hepatocelular, bem como metástase de carcinoma, provavelmente do ducto biliar.CONCLUSÃO:Apesar do carcinoma apresentado pela paciente, o uso de nimesulida pode ter contribuído para o dano hepático. Até que esta questão seja esclarecida, a prescrição de nimesulida deve ser cuidadosa para pacientes com doenças hepáticas.

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.

Healthcare resource utilization and costs of outpatient follow-up after liver transplantation in a university hospital in São Paulo, Brazil: cost description study / Utilização de recursos em saúde e custos do acompanhamento ambulatorial pós-transplante de fígado em um hospital universitário em São Paulo, Brasil: estudo de descrição de custos

CONTEXT AND OBJECTIVE: Data on the costs of outpatient follow-up after liver transplantation are scarce in Brazil. The purpose of the present study was to estimate the direct medical costs of the outpatient follow-up after liver transplantation, from the first outpatient visit after transplantation to five years after transplantation. DESIGN AND SETTING: Cost description study conducted in a university hospital in São Paulo, Brazil. METHODS: Cost data were available for 20 adults who underwent liver transplantation due to acute liver failure (ALF) from 2005 to 2009. The data were retrospectively retrieved from medical records and the hospital accounting information system from December 2010 to January 2011. RESULTS: Mean cost per patient/year was R$ 13,569 (US$ 5,824). The first year of follow-up was the most expensive (R$ 32,546 or US$ 13,968), and medication was the main driver of total costs, accounting for 85% of the total costs over the five-year period and 71.9% of the first-year total costs. In the second year after transplantation, the mean total costs were about half of the amount of the first-year costs (R$ 15,165 or US$ 6,509). Medication was the largest contributor to the costs followed by hospitalization, over the five-year period. In the fourth year, the costs of diagnostic tests exceeded the hospitalization costs. CONCLUSION: This analysis provides significant insight into the costs of outpatient follow-up after liver transplantation due to ALF and the participation of each cost component in the Brazilian setting. .

CONTEXTO E OBJETIVO: Dados sobre os custos do seguimento ambulatorial pós-transplante de fígado são escassos no Brasil. O objetivo do presente estudo foi estimar os custos diretos médicos do seguimento ambulatorial pós-transplante de fígado a partir da primeira visita ambulatorial pós-transplante até cinco anos após o transplante. TIPO DE ESTUDO E LOCAL: Estudo de descrição de custos realizado em um hospital universitário em São Paulo, Brasil. MÉTODOS: Dados de custos estavam disponíveis para 20 adultos que foram submetidos a transplante de fígado devido a insuficiência hepática aguda (IHA) de 2005 a 2009. Os dados foram retrospectivamente obtidos em prontuários médicos e no sistema de informação contábil hospitalar de dezembro de 2010 a janeiro de 2011. RESULTADOS: A média de custo por paciente/ano foi de R$ 13.569 (US$ 5.824). O primeiro ano de acompanhamento foi o mais caro, R$ 32.546 (US$ 13,968), e medicação foi o principal impulsionador dos custos totais, respondendo por 85% dos custos totais no período de cinco anos e 71,9% dos custos totais do primeiro ano. No segundo ano pós-transplante, os custos médios totais foram cerca da metade do montante de custos do primeiro ano (R$ 15.165 ou US$ 6,509). Medicação foi o maior contribuinte para os custos seguido da internação, no período de cinco anos. No quarto ano, os custos dos testes diagnósticos superam os custos de internação. CONCLUSÃO: Esta análise proporciona uma compreensão significativa dos custos do seguimento ambulatorial pós-transplante de fígado por IHA e a participação de cada componente de custo no cenário brasileiro. .

Hipotermia terapêutica como ponte até transplante em pacientes com falência hepática fulminante / Therapeutic hypothermia as a bridge to transplantation in patients with fulminant hepatic failure

Os tópicos mais importantes na falência hepática fulminante são o edema cerebral e a hipertensão intracraniana. Dentre todas as opções terapêuticas, tem sido relatado que a hipotermia sistêmica induzida em níveis entre 33 - 34ºC reduz a elevação da pressão e aumenta o tempo durante o qual os pacientes podem tolerar um enxerto. Esta revisão discutiu as indicações e os efeitos adversos da hipotermia.

The most important topics in fulminant hepatic failure are cerebral edema and intracranial hypertension. Among all therapeutic options, systemic induced hypothermia to 33 - 34ºC has been reported to reduce the high pressure and increase the time during which patients can tolerate a graft. This review discusses the indications and adverse effects of hypothermia.

The effects of anesthetic regimen in 90% hepatectomy in rats / Os efeitos do regime anestésico na hepatectomia de 90% em ratos

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63±31.7 mg/dL) than in the isoflurane group (98±21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

OBJETIVO: Avaliar a influência do regime anestésico sobre a recuperação anestésica, a sobrevida em 72 horas e a glicemia após hepatectomia parcial de 90% em ratos. MÉTODOS: Trinta ratos Wistar machos adultos foram distribuídos em dois grupos conforme o regime anestésico: combinação de ketamina e xilazina intraperitoneal ou isoflurano inalatório. Para prevenção de hipoglicemia foi administrada glicose intraperitoneal e adicionado glicose (20%) na água de beber. RESULTADOS: A recuperação anestésica no grupo ketamina e xilazina foi mais prolongada. Durante primeira hora após hepatectomia, nenhum rato anestesiado com ketamina e xilazina despertou. Todos do grupo isoflurano estavam ativos minutos após final da cirurgia. A sobrevida em 72 horas foi menor (Log rank=0,0001) no grupo ketamina e xilazina (0,0%) que no grupo isoflurano (26,7%). Glicemia em 6 horas do grupo ketamina e xilazina (63±31,7 mg/dL) foi menor (p=0,017) que no grupo isoflurano (98 ±21,2 mg/dL). Prolongado tempo de recuperação anestésica com ketamina e xilazina diminuiu sobrevida e glicemia após hepatectomia 90%. CONCLUSÃO: Anestesia com isoflurano reduziu tempo de recuperação e hipoglicemia, além de aumentar a sobrevida nas primeiras horas, possibilitando uma janela terapêutica adequada para estudos experimentais.

The effects of anesthetic regimen in 90% hepatectomy in rats / Os efeitos do regime anestésico na hepatectomia de 90% em ratos

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63±31.7 mg/dL) than in the isoflurane group (98±21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.(AU)

OBJETIVO: Avaliar a influência do regime anestésico sobre a recuperação anestésica, a sobrevida em 72 horas e a glicemia após hepatectomia parcial de 90% em ratos. MÉTODOS: Trinta ratos Wistar machos adultos foram distribuídos em dois grupos conforme o regime anestésico: combinação de ketamina e xilazina intraperitoneal ou isoflurano inalatório. Para prevenção de hipoglicemia foi administrada glicose intraperitoneal e adicionado glicose (20%) na água de beber. RESULTADOS: A recuperação anestésica no grupo ketamina e xilazina foi mais prolongada. Durante primeira hora após hepatectomia, nenhum rato anestesiado com ketamina e xilazina despertou. Todos do grupo isoflurano estavam ativos minutos após final da cirurgia. A sobrevida em 72 horas foi menor (Log rank=0,0001) no grupo ketamina e xilazina (0,0%) que no grupo isoflurano (26,7%). Glicemia em 6 horas do grupo ketamina e xilazina (63±31,7 mg/dL) foi menor (p=0,017) que no grupo isoflurano (98 ±21,2 mg/dL). Prolongado tempo de recuperação anestésica com ketamina e xilazina diminuiu sobrevida e glicemia após hepatectomia 90%. CONCLUSÃO: Anestesia com isoflurano reduziu tempo de recuperação e hipoglicemia, além de aumentar a sobrevida nas primeiras horas, possibilitando uma janela terapêutica adequada para estudos experimentais.(AU)

Sistemas de soporte hepático extracorpóreo: [revisión] / Extracorporeal liver support systems: [review]

Introducción. Los sistemas de soporte hepático extracorpóreo (SHE) surgen como una alternativa al trasplante hepático (TH), dado el incremento en la incidencia de falla hepática aguda (FHA), falla hepática crónica agudizada (FHCA), así como las restricciones en la oferta de órganos. Objetivo. Revisión de la literatura de los sistemas de soporte hepático extracorporeo. Metodología. Búsqueda de la literatura publicada entre julio de 1990 y noviembre de 2010 en las principales bases de datos médicas que incluyeron MEDLINE, SciELO y EMBASE, de artículos que analizaran tecnologías relacionadas con sistemas de soporte hepático en cuanto a sus especificaciones técnicas, sus usos y la evidencia respecto a su efectividad en pacientes con algún tipo de falla hepática que requirieran soporte.Resultados. Estos sistemas pueden dividirse en artificiales (hemofiltración, sistema MARS) y bioartificiales (como el Hepatassist™). Su fundamento consiste en reemplazar los procesos de destoxificación relacionados específicamente con el sistema de bilirrubinas, la eliminación de aminoácidos aromáticos, agentes inflamatorios y el manejo de los productos de degradación del sistema de la coagulación. Los recientes avances en bioingeniería y biogenética han hecho que estas tecnologías se acerquen cada vez más a una forma ideal, permitiendo que sean utilizados con relativo éxito en humanos. Los SHE, en su gran mayoría en desarrollo, pretenden no solo actuar como puente al TH, sino que, en casos puntuales, pueden llegar a ser la piedra angular del tratamiento mientras la FHA logra resolverse.

Background. Extracorporeal liver support systems (ELS) have emerged as an alternative to liver transplant (LT), given the growing incidence of acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and the limited organ supply. Objective. Review of literature about Extracorporeal Liver Support Systems. Methodology. A literature search was conducted on the main medical databases including MEDLINE, SciELO and EMBASE for papers published between July 1990 and November 2010 looking at technologies associated with liver support systems, their technical specifications, their use, and evidence regarding their effectiveness in patients with some forms of liver failure requiring support. Results. These systems may be divided into artificial (hemofiltration, MARS) and bioartificial (such as the Hepatassist™). They work by replacing detoxification processes associated specifically with bilirubins, aromatic aminoacids, and inflammatory agents, and the elimination of breakdown products of coagulation. Recent advances in bioengineering and biogenetics have brought these technologies closer to hetheideal, enabling their use in humans with a relative degree of success. ELS systems, most of them still under development, are designed not only to act as a bridge for LT but may also become the cornerstone of treatment in specific cases while the ALF resolves.

Hepatic necrosis associated with drug-induced hypersensitivity syndrome.

Drug-induced hypersensitivity syndrome (DIHS; also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) is a life-threatening condition first described by Chaiken et al. in 1950. It is characterized by extensive mucocutaneous rash; fever; lymphadenopathy; hepatitis; hematological abnormalities; damage to several organs such as kidney, heart, lungs, and pancreas; and possible reactivation of human herpesvirus-6 (HHV-6) or other herpes virus. Rare and severe cases may present hepatic necrosis, and about 15% of them result in death or liver transplantation. A hallmark of this syndrome is the late onset of symptoms after the drug exposure. The most common culprit drugs are the aromatic anticonvulsants (in almost 30% of the cases) and the antibiotics (which in some series represent 20% of the cases). The authors report a case of a 41-year-old female who presented to the emergency department with erythroderma, acute hepatitis, acute pancreatitis and acute renal failure, and was then treated with corticosteroid after the diagnosis of DIHS/DRESS. A specific culprit drug could not confidently be determined due to the presence of multiple drugs used by the patient. The clinical and laboratory outcome was apparently satisfactory, but unexpectedly, on the sixth day of hospitalization, the patient complained of nonspecific malaise, drowsiness, which progressed in a few hours with signs and symptoms of hepatic failure, refractory shock, and death. The autopsy findings showed submassive hepatic necrosis, and the immediate cause of death was attributed to hepatic failure.

Falla hepática fulminante por virus hepatitis B en paciente coinfectado por VIH: un desafío terapéutico. Caso clínico / Fulminant hepatic failure by hepatitis B virus in a patient with human immunodeficiency virus infection: Report of one case

The human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection is a common problem in the world, with an estimated prevalence of up to 8 percent. We report a 27-year-old man admitted to the intensive care unit with an acute liver failure by HBV. During hospital stay, a co-infection with HIV virus was detected. Treatment with early antiviral therapy was started with emtricitabine, tenofovir and raltegravir, to cover both HBV and HIV. Despite therapy, the patient died two weeks after admission.

A new experimental model for acute hepatic failure in rats / Novo modelo experimental em ratos para insuficiência hepática aguda

PURPOSE: To develop a reliable surgical model of acute hepatic failure and hyperammonemia in rats that avoids porto-systemic shunt and bile duct ligation, applicable to hepatic encephalopathy research. METHODS: The pedicles of right lateral and caudate lobes were exposed and clamped. One hour later, the animal was reopened, clamps were released and anterior subtotal hepatectomy (resection of median and left lateral lobes) was performed, comprising 75 percent of liver removal. Four hours after hepatectomy, blood samples and liver tissues were collected from ALF and control groups. RESULTS: Differences between ALF and control groups were significant for ALT, AST, total and direct bilirubin, sodium, potassium, alkaline phosphatasis, gamma-glutamyltransferase and most important, ammonia. Histologically, significant differences were noticed between groups. CONCLUSION: The model is useful for the study of specific aspects of ALF and the development of new therapeutic approaches.

OBJETIVO: Desenvolver um modelo cirúrgico de IHA e hiperamonemia em ratos, que evita o shunt porto-sistêmico e a ligadura do ducto biliar, que seja aplicável à pesquisa de encefalopatia hepática. MÉTODOS: Após anestesia geral e laparotomia mediana, os pedículos dos lobos laterais direito e caudado foram isolados e clampeados. Após 1 hora, o animal foi reaberto, os clampes retirados e foi realizada hepatectomia anterior subtotal (ressecção dos lobos médio e lateral esquerdo), compreendendo a remoção de 75 por cento do parênquima. Quatro horas após a hepatectomia, amostras de sangue e tecido hepático foram coletadas nos grupos IHA e controle. RESULTADOS: Diferenças entre os grupos IHA e controle foram significativas para ALT, AST, bilirrubina total e direta, sódio, potássio, fosfatase alcalina, gama glutamiltransferase e principalmente amônia. Histologicamente, diferenças significativas foram observadas entre os grupos. CONCLUSÃO: O modelo é útil para o estudo de aspectos específicos da IHA e o desenvolvimento de novas abordagens terapêuticas.