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Resumen: La insuficiencia hepática aguda es una enfermedad poco común pero que amenaza la vida y afecta con mayor frecuencia a pacientes que no tienen enfermedades preexistentes del hígado. El paracetamol (acetaminofén) es uno de los medicamentos analgésicos-antipiréticos prescritos con más frecuencia por los médicos y automedicados por las personas, cuyos efectos adversos son desde molestias leves hasta efectos adversos letales, que no necesariamente requieren la dosis tóxica para causar tales efectos graves. No es sorprendente que el paracetamol sigue siendo causa importante de sobredosis: desde intoxicaciones intencionadas (suicida) y no intencionadas (consumo crónico), cuyos efectos graves van desde la insuficiencia hepática fulminante relacionada con sobredosis hasta la muerte; la mitad de estos episodios se atribuyen al paracetamol y estos casos parecen estar aumentando cada vez más debido a su fácil acceso y venta libre. El objetivo de este artículo es comunicar un caso y revisar la bibliografía al respecto.
Abstract: Acute liver failure is a rare disease but life-threatening, and occurs more frequently in patients without preexisting liver disease. Paracetamol (acetaminophen) is one of the analgesic-antipyretic drugs most frequently prescribed by physicians and self- medicated by people, whose adverse effects are mild discomfort and even lethal side effects that do not necessarily require the toxic dose to cause such serious effects. Not surprisingly, acetaminophen remains a major cause of overdose: from intentional poisoning (suicide) and unintentional (chronic use), whose major effects are ranging from fulminant hepatic failure related to overdose to death; half of these episodes are attributable to paracetamol, and these cases seem to be increasing more and more, because of its easy access and free sale. The aim of this paper is to present a case report and a literature review.
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INTRODUCTION AND AIM: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. MATERIAL AND METHODS: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. RESULTS: A total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). CONCLUSIONS: Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.
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Falência Hepática Aguda/cirurgia , Transplante de Fígado , Listas de Espera , Adulto , Argentina/epidemiologia , Técnicas de Apoio para a Decisão , Feminino , Sobrevivência de Enxerto , Nível de Saúde , Indicadores Básicos de Saúde , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/mortalidade , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Obtenção de Tecidos e Órgãos , Resultado do Tratamento , Listas de Espera/mortalidade , Adulto JovemRESUMO
Despite the increasing incidence of syphilis and due to its wide variety of clinical manifestations, syphilis remains an under-diagnosed condition. We report an unusual case of secondary syphilis presenting with acute hepatitis and skin lesions, confirmed based on positive treponemal and non-treponemal assays. Despite adequate diagnosis and treatment, the patient developed fulminant hepatitis and brain death. This atypical presentation emphasizes the importance of high clinical suspicion in recognizing syphilis as an etiology for unexplained acute hepatitis, allowing early diagnosis and treatment and possibly avoiding severe complications such as fulminant hepatic failure.
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Hepatite/complicações , Falência Hepática Aguda/etiologia , Sífilis/complicações , Adolescente , Morte Encefálica , Evolução Fatal , Feminino , Humanos , Testes de Função Hepática , Sífilis/diagnóstico , Sorodiagnóstico da SífilisRESUMO
Hepatic encephalopathy (HE) represents a serious complication of acute liver failure (ALF) in which cerebral edema leading to brainstem herniation as a result of increased intracranial hypertension is a major consequence. Long non-coding RNAs (lncRNAs) play a significant role in coordinating gene expression, with recent studies indicating an influence in the pathogenesis of several diseases. To investigate their involvement in the cerebral pathophysiology of ALF, we profiled the expression of lncRNAs in the frontal cortex of mice at coma stage following treatment with the hepatotoxin azoxymethane. Of the 35,923 lncRNAs profiled using microarrays, 868 transcripts were found to be differentially expressed in the ALF-treated group compared to the sham control group. Of these, 382 lncRNAs were upregulated and 486 lncRNAs downregulated. Pathway analysis revealed these lncRNAs target a number of biological and molecular pathways that include cytokine-cytokine receptor interaction, the mitogen activated protein kinase signaling pathway, the insulin signaling pathway, and the nuclear factor-κB signaling pathway. False discovery rate adjustment identified 9 upregulated lncRNAs, 2 of which are associated with neuroepithelial transforming gene 1 (NET1) and the monocarboxylate transporter 2 (Slc16a7), potential contributors to astrocyte cytoskeletal disruption/swelling and lactate production, respectively. Our findings suggest an important role for lncRNAs in the brain in ALF in relation to inflammation, neuropathology, and in terms of the functional basis of HE. Further work on these non-coding RNAs may lead to new therapeutic approaches for the treatment and management of cerebral dysfunction resulting from this potentially life-threatening disorder.
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Córtex Cerebral/metabolismo , Falência Hepática Aguda/genética , RNA Longo não Codificante/metabolismo , Animais , Falência Hepática Aguda/metabolismo , Masculino , Camundongos Endogâmicos C57BLRESUMO
Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.
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Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Técnicas de Apoio para a Decisão , Progressão da Doença , Humanos , Falência Hepática Aguda/complicações , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/mortalidade , Transplante de Fígado/mortalidade , Seleção de Pacientes , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To describe the clinical manifestations and outcome of acute liver failure (ALF) associated with dengue viral infection, a rare but severe complication. METHODS: One hundred and fifty five consecutive patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described. RESULTS: All patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum) age was 33.5 (17, 47) years with 50% female. The median (minimum, maximum) duration from the onset of fever to development of ALF was 7.5 (5, 13) days and the maximum hepatic encephalopathy (HE) grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS) on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase [median admission 1140.5 u/L (639, 4161); median peak 2487 u/L (998, 5181)], serum bilirubin [median admission 29 µmol/L (23, 291); median peak 127 µmol/L (72, 592)], and prothrombin time [median admission 16.8 s (15.3, 26.2); median peak 22 s (15.3, 40.7)]. The survival rate with standard medical therapy alone was 100%. CONCLUSIONS: Dengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Dengue/complicações , Hepatite Viral Humana/virologia , Falência Hepática Aguda/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
A encefalopatia hepática (EH) é um distúrbio funcional do sistema nervoso central (SNC) associado à insufi ciência hepática, de fisiopatologia multifatorial e complexa. Devido aos avanços no conhecimento sobre o manejo da EH na cirrose e na insuficiência hepática aguda (IHA), a diretoria da Sociedade Brasileira de Hepatologia (SBH) promoveu uma reunião monotemática acerca da fi siopatologia, diagnóstico e tratamento da EH, abordando aspectos controversos relacionados ao tema. Com a utilização de sistemática da medicina baseada em evidências, foram abordados o manejo da EH e da hipertensão intracraniana na IHA, o manejo da EH episódica na cirrose, as controvérsias no manejo da EH e a abordagem da EH mínima. O objetivo desta revisão é resumir os principais tópicos discutidos na reunião monotemática e apresentar recomendações sobre o manejo da síndrome votadas pelo painel de expertos da SBH.
Hepatic encephalopathy (HE) is a functional disorder of the central nervous system (CNS) associated with liver failure, either end-stage chronic liver disease or fulminant hepatic failure. Its pathogenesis remains complex and poorly understood. In view of recent advances in the management of HE, the Brazilian Society of Hepatology endorsed a monothematic meetingregarding HE in order to gather experts in the to discuss related data and to draw evidence-based recommendations concerning: management of HE and intracranial hypertension in FHF, treatment of episodic HE in cirrhosis, controversies in the management of EH including difficult to treat cases and diagnostic and treatment challenges for minimal HE. The purpose of this review is to summarize the lectures and recommendations made by the panel of experts of the Brazilian Society of Hepatology.
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Humanos , Encefalopatia Hepática , Fibrose , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/fisiopatologia , Transplante de Fígado , Falência Hepática Aguda , Hipertensão Intracraniana/prevenção & controle , Amônia , Hipertensão PortalRESUMO
Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.
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Animais , Humanos , Camundongos , Imunoglobulina A Secretora/imunologia , Falência Hepática Aguda/imunologia , Estudos de Casos e Controles , Imunofluorescência , Imuno-Histoquímica , Imunidade nas Mucosas/imunologia , Imunoglobulina A Secretora/metabolismo , Mucosa Intestinal/imunologia , Falência Hepática Aguda/metabolismo , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo RealRESUMO
INTRODUCTION: Hepatitis A virus (HAV) infection is a vaccine-preventable disease. The most severe complication in children is fulminant hepatic failure (FHF), estimated to occur in 0.4% of cases; patients with FHF often require a liver transplant (LT). Following another outbreak of HAV infection in Argentina during 2003-2004, a one-dose HAV universal immunization (UI) program was started in 2005, resulting in a reduction in the incidence of HAV infection. We have investigated the impact of HAV UI on the trends in the occurrence of FHF and LT in children. METHODS: All pediatric cases of FHF admitted to four pediatric centers in Buenos Aires during March 1993-July 2005 were retrospectively reviewed, and data of cases during August 2005-December 2008 were collected. Information about demography, HAV infections and vaccination status, diagnostic data for FHF using the Pediatric Acute Liver Failure criteria, clinical laboratory results, encephalopathy, the severity of liver disease using the Pediatric End Stage Liver Disease score, assessment of patients on the LT waiting list using King's College Criteria for LT, treatment given for FHF (pre- and post-transplant), and clinical outcome were collected using a case report form. The frequency and outcomes of HAV-associated FHF and LT cases before and after UI were analyzed. RESULTS: During the pre-immunization period, March 1993-July 2005, 54.6% (N = 165) of FHF cases were caused by HAV; HAV-associated FHF cases peaked during 2003-2004. During the post-immunization period, August 2005-December 2008, only 27.7% (N = 18) of FHF cases were caused by HAV infection; only one of these patients had received the HAV vaccine (one dose only). The number of HAV-associated FHF cases decreased from 2005, and no cases were reported from November 2006-December 2008. Multivariate analyses showed that the association of FHF with HAV infection rather than other etiologies decreased with increasing age (P = 0.03), UI against HAV (P = 0.002), and anti-actin antibodies (P = 0.002), and increased with increasing weight (P = 0.0004). CONCLUSIONS: The number of children with HAV-associated FHF in Argentina has strongly decreased since the initiation of the UI program. Further monitoring is required to confirm the long-term health and economic benefits of UI against HAV infection.
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BACKGROUND: Elevated intracranial pressure (ICP) is a common cause of death in acute liver failure (ALF) and is determinant for decision-making regarding the timing of liver transplantation. The recommended type ICP monitoring device is controversial in ALF patients. Epidural devices had less risk of hemorrhagic complications, but they are less reliable than intraparenchymal ones. METHOD: Twenty-three patients with ALF were treated, and 19 of them received a liver transplant. Seventeen patients had ICP monitoring because of grade III-IV encephalopathy. All patients received fresh plasma (2-3 units) before and during placing the intraparenchymal device. RESULTS: Eleven cases (64.7 percent) had elevated ICP, and 6 patients (35.2 percent) had normal values. One patient (5.9 percent) had an asymptomatic small intraparenchymal haemorrhage <1cm³ in CTscan, which did not prevent the liver transplantation. CONCLUSION: In our experience, intraparenchymal ICP monitoring in patients with ALF seems to be an accurate method with a low risk of complications.
ANTECEDENTES: La presión intracraneana elevada (PIC) es una causa frecuente de muerte en la falla hepática aguda (FHA) y es determinante para la toma de decisiones respecto del momento del transplante hepático. El tipo de dispositivo para el monitoreo de OIC es controversial em los pacientes em FHA. Los dispositivos epidurales tienen menos riesgo de complicaciones hemorrágicas, pero son menos confiables que los intraparenquimatosos. MÉTODO: Veintitrés pacientes con FHA fueron tratados, y 19 de ellos recibieron un transplante hepático. diecisiete pacientes tuvieron monitoreo de PIC debido a encefalopatía grado III-IV. Todos los pacientes recibieron plasma fresco (2-3 unidades) antes y durante la colocación de la fibra intraparenquimatosa. RESULTADOS: Once casos (64.7 por ciento) tuvieron PIC elevada, y 6 pacientes (35.2 por ciento) tuvieron valores normales. Un paciente (5.9 por ciento) tuvo una pequeña hemorragia intraparenquimatosa asintomática <1cm³ en TAC, la cual no impidió el transplante hepático. CONCLUSIÓN: En nuestra experiencia, el monitoreo intraparenquimatoso de presión intracraneana en pacientes con FHA parece ser un método preciso y con bajo riesgo de complicaciones.
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Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Hipertensão Intracraniana/etiologia , Pressão Intracraniana/fisiologia , Transplante de Fígado , Falência Hepática Aguda/complicações , Monitorização Fisiológica/métodos , Distribuição por Idade , Falência Hepática Aguda/cirurgia , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
El trasplante hepático (TH) está indicado en pacientes con enfermedades hepáticas agudas o crónicas severas e irreversibles para las cuales no exista un tratamiento alternativo y en ausencia de contraindicaciones. Las indicaciones de TH pueden ser agrupadas en cuatro categorías: cirrosis hepática, hepatitis fulminante, tumores hepáticos y defectos genéticos de origen hepático que producen daño en otros órganos. Deben ser derivados para TH los pacientes con cirrosis que desarrollen cualquier complicación mayor o coagulopatía. La derivación precoz es "la clave del éxito" en la hepatitis fulminante por el alto riesgo de muerte y por tener una evolución mayormente impredecible. La oportunidad del TH es el momento en la historia natural de la hepatopatía cuando la sobrevida esperada es mayor con TH que en lista de espera. Estudios recientes han sugerido que el máximo beneficio del TH se obtiene en pacientes con MELD >15. Sin embargo, en algunos casos sin riesgo de muerte inminente, el objetivo del TH es mejorar la calidad de vida o prevenir contraindicaciones como la progresión del hepatocarcinoma cuando el tiempo de espera excede los 8 meses. Actualmente existe una marcada desproporción entre el número de donantes disponibles y el número creciente de potenciales receptores, lo que ha determinado un incremento progresivo del tiempo y mortalidad en lista. La racionalidad de distribuir los órganos en base al score de MELD es otorgar prioridad en la lista a los candidatos más enfermos y a aquellos que no pueden esperar como los pacientes con hepatocarcinoma.
Liver transplantation (OLT) is indicated in patients with severe and irreversible acute or chronic liver disease without alternative therapy and in the absence of contraindications. Indications for OLT can be grouped in four categories, namely cirrhosis, fulminant hepatitis, malignant hepatic tumors and liver-based genetic defects that trigger damage of other organs. Patients with cirrhosis should be referred for OLT after the onset of any of the major complications or coagulopathy. Early referral is crucial in fulminant hepatitis due to the high mortality with medical therapy and the unpredictable nature of this condition. Ideal timing for OLT is the moment in the natural history of the disease when the expected survival of patients on the waiting list is higher with than without OLT. Recent data suggest that maximal benefit of OLT is obtained in patients with a MELD score >15. However, in some cases with no imminent risk of death, OLT is indicated to improve quality of life or to prevent contraindications such as progression of hepatocellular carcinoma. At present, there is a marked disproportion between the number of donors available and the growing number of patients listed worldwide, which in turn has resulted in prolongation of the time-interval to OLT and waitlist mortality. The rationale of allocation systems utilizing the MELD score is to prioritize on the waiting list patients with severe liver dysfunction ("the sickest first") and those with hepatocellular carcinoma who may loose the benefits of OLT when waitlist time exceeds eight months.