Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes / 中华肝脏病杂志

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

Clinical characteristics of Wilson's disease with onset of acute liver failure in 19 children / 中华儿科杂志

Objective: To analyze the clinical characteristics of Wilson's disease (WD) with onset of acute liver failure (ALF) in children. Methods: Clinical data of 19 children diagnosed with WD presented with ALF in Xi'an Children's Hospital from January 2016 to April 2021 were retrospectively analyzed, including general condition, clinical manifestation, laboratory examination, and gene detection. The children were divided into the death group and survival group according to the clinical outcome. The children who had hepatic WD with non-ALF onset during the same period were selected as the control. The general conditions and laboratory indexes were compared between death group and survival group, ALF group and non-ALF group. T-test, Mann Whitney U test or χ2 test were used to compare the differences between the two groups. Results: Of the 19 WD children with ALF onset, 10 were females and 9 were males. The age of admission was (10.1±2.6) years and time to onset of first visit was 9 (4, 15) days. Among the WD children with ALF onset, 4 children were lost to follow-up, 5 cases death (death group) and 10 cases survived (survival group). The ceruloplasmin in the death group was higher than that in the survival group (0.078 (0.055, 0.105) vs. 0.033 (0.027, 0.058) g/L, Z=-2.33, P=0.020). There were 95 children who had hepatic WD with non-ALF onset. The WD patients with ALF onset were older at admission (9.9 (8.0, 11.1) vs. 5.4 (3.7, 6.9) years, Z=-5.25, P<0.001), had higher ceruloplasmin (0.060 (0.030, 0.078) vs. 0.024 (0.006, 0.060) g/L, Z=-3.11, P=0.002), 24 h urinary copper (674 (205, 1 803) vs. 149 (108, 206) μg, Z=-4.25, P<0.001), and positive rate of K-F ring [17/19 vs. 7%(7/95), χ2=50.17, P<0.001] while shorter onset time at initial visit (0.3 (0.1, 0.5) vs. 1.0 (0.7, 6.0) months, Z=-4.28, P<0.001). There was no gender difference between the two groups [9/19 vs. 61%(58/95), χ2=1.22, P=0.269]. Of the 19 WD children with ALF onset, 13 had the ATP7B gene tested, and 15 reported variants were detected. The main variations were c.2333G>T (p. Arg778Leu), c.2621C>T (p. Ala874Val) and c.2975C>T (p. Pro992Leu). The allele frequencies were 6/26(23%), 4/26(15%) and 3/26(12%), respectively. Conclusions: Children of WD onset with ALF are school-aged and above. They have an acute onset, a short course of the disease, and poor prognosis. The positive rate of K-F ring, ceruloplasmin and urinary copper are higher than those of the hepatic WD children with non-ALF onset.

Application of double plasma molecular adsorption system in children with acute liver failure / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of double plasma molecular absorption system (DPMAS) in the treatment of pediatric acute liver failure (PALF).@*METHODS@#A prospective analysis was performed on the medical data of children with PALF who were hospitalized in the Intensive Care Unit (ICU), Hunan Children's Hospital, from March 2018 to June 2020. The children were randomly divided into two groups:plasma exchange group (PE group) and DPMAS group (@*RESULTS@#Compared with the PE group, the DPMAS group had a significantly lower number of times of artificial liver support therapy and a significantly shorter duration of ICU stay (@*CONCLUSIONS@#DPMAS is safe and effective in the treatment of PALF and can thus be used as an alternative to artificial liver support therapy.

Falla hepática aguda en pediatría / Pediatric acute liver failure

Resumen: La falla hepática aguda (FHA) es poco frecuente en pediatría, amenaza la vida y requiere aborda je multidisciplinario para su diagnóstico y tratamiento tempranos. El presente artículo tiene como objetivo realizar actualización de definiciones, enfoques y tratamientos disponibles. Los artículos se obtuvieron de la revisión de la literatura disponible entre 2000 y 2020 en varias bases de datos (Pub- med, LILACS, BIREME, Google Académico y UpToDate), empleando términos "acute liver failure" en Pubmed, "pediatric acute liver failure", "falla hepática aguda en pediatría" para otros buscadores y aplicando filtros según edad, fecha de publicación y tipo de estudio (ensayos clínicos, artículos de revisión, revisiones sistemáticas, estudios de casos y controles), se eligieron aquellos artículos con mayor número de citaciones y con datos recientes. La FHA requiere soporte en cuidado intensivo pe diátrico y su diagnóstico temprano favorece la instauración del tratamiento. Se recomienda el enfo que de pruebas diagnósticas específicas por edad en pacientes pediátricos con FHA. No hay consenso acerca de las indicaciones de trasplante hepático en FHA en pediatría.

Abstract: Acute liver failure (ALF) is a rare and life-threatening entity in pediatrics which requires a multidis ciplinary approach for early diagnosis and treatment. The objective of this article is to update defi nitions, management, and available treatments. We obtained the articles by reviewing the literature available between 2000 and 2020 in different databases (Pubmed, LILACS, BIREME, Google Scholar, and UpToDate), using terms such as "acute liver failure" in Pubmed, and in other databases "pedia tric acute liver failure" and "falla hepática aguda en pediatría" using filters such as age, publication date, and types of study (clinical trials, review articles, systematic reviews, and case-control studies). We chose those articles with the highest number of citations and with recent data. The ALF requires support in the pediatric intensive care unit and its early diagnosis favors the beginning of treatment. In pediatric patients with ALF, it is recommended to focus on age-specific diagnostic testing. There is no agreement regarding the liver transplantation in pediatric cases of ALF.

Falla hepática aguda / Acute liver failure

La falla hepática aguda es la pérdida súbita de la función hepática en un corto plazo en un paciente sin enfermedad hepática previa, que se acompaña de coagulopatía y encefalopatía. Es una entidad rara con una incidencia muy baja que afecta especialmente a personas jóvenes. La principal causa en países desarrollados es la toxicidad por acetaminofén, mientras que en los países subdesarrollados son las hepatitis virales. El curso natural de la enfermedad es la progresión rápida a muerte por falla orgánica multisistémica, sepsis o edema cerebral. Después del diagnóstico, los pacientes deben remitirse tempranamente a la unidad de cuidado intensivo y a centros que ofrezcan trasplante hepático. La supervivencia sin trasplante hepático hasta hace pocos años era menor al 15%; sin embargo, en la actualidad puede ser hasta del 50%, dependiendo de la causa, y está relacionada con tratamientos específicos, la disponibilidad de trasplante hepático y una atención óptima en las unidades de cuidados intensivos. El trasplante hepático se constituye en el tratamiento de elección para los pacientes con falla hepática aguda y criterios de mal pronóstico del King's College.

Acute liver failure is the severe short-term liver function impairment in a patient without previous liver disease, which is accompanied by coagulopathy and encephalopathy. It is a rare condition with a very low incidence that affects young people. The leading cause in developed countries is acetaminophen toxicity, while in developing countries is mainly caused by viral hepatitis. The natural course is characterized by a rapid progression to death due to multisystemic organ failure, sepsis, or cerebral edema. After diagnosis, patients must be transferred to the intensive care unit and liver transplantation centers. Survival without liver transplantation until a few years ago was less than 15%; however, currently it can be up to 50% depending on the cause, and it is related to specific treatments, availability of liver transplantation and optimal care in the intensive care units. Liver transplantation is the treatment of choice for patients with acute liver failure and King's College criteria for poor prognosis.

Hepatitis autoinmune en la edad pediátrica / Autoimmune hepatitis in the pediatric age

Resumen: En pediatría, la hepatitis autoinmune y la colangitis esclerosante son patologías de afección hepática cuyo mecanismo de daño es inmunológico. La hepatitis autoinmune es una enfermedad de etiología desconocida, caracterizada por hepatitis de interfase, hipergammaglobulinemia, autoanticuerpos circulantes y una respuesta favorable a la inmunosupresión. Es una enfermedad eminentemente pediátrica, con una afección prevalente hacia mujeres jóvenes. La terapia debe ser instituida con prontitud para prevenir el deterioro rápido, promover la remisión de la enfermedad y la supervivencia a largo plazo. La falta persistente de respuesta o la falta de adherencia al tratamiento dan como resultado una enfermedad hepática terminal. Los pacientes que desarrollan esta patología, y aquellos con insuficiencia hepática fulminante en el momento del diagnóstico, requerirán trasplante hepático.

Abstract: In pediatrics, autoimmune hepatitis and sclerosing cholangitis are liver disorders with an immunological damage mechanism. Autoimmune hepatitis is a disease of unknown etiology characterized by interface hepatitis, hypergammaglobulinemia, circulating autoantibodies and a favorable response to immunosuppression. It is an eminently pediatric disease with a prevalent condition in young women. Therapy should be instituted promptly to prevent rapid deterioration, promote remission of disease and long-term survival. The persistent lack of response or lack of adherence to treatment results in terminal liver failure; these patients, and those with fulminant hepatic insufficiency at the time of diagnosis, will require liver transplantation.

Evaluating the best time to intervene acute liver failure in rat models induced by d-galactosamine

ABSTRACT PURPOSE: To describe an animal model for acute liver failure by intraperitoneal d-galactosamine injections in rats and to define when is the best time to intervene through King's College and Clichy´s criteria evaluation. METHODS: Sixty-one Wistar female rats were distributed into three groups: group 1 (11 rats received 1.4 g/kg of d-galactosamine intraperitoneally and were observed until they died); group 2 (44 rats received a dose of 1.4 g/kg of d-galactosamine and blood and histological samples were collected for analysis at 12 , 24, 48 , 72 and 120 hours after the injection); and the control group as well (6 rats) . RESULTS: Twelve hours after applying d-galactosamine, AST/ALT, bilirubin, factor V, PT and INR were already altered. The peak was reached at 48 hours. INR > 6.5 was found 12 hours after the injection and factor V < 30% after 24 hours. All the laboratory variables presented statistical differences, except urea (p = 0.758). There were statistical differences among all the histological variables analyzed. CONCLUSION: King's College and Clichy´s criteria were fulfilled 12 hours after the d-galactosamine injection and this time may represent the best time to intervene in this acute liver failure animal model.

ERK 1/2 activation does not contribute to increased survival mediated by bone marrow cells after 90% partial hepatectomy in Wistar rats

We investigated the influence of bone marrow cells upon activation of ERK 1/2 in an animal model of 90% PH. Phosphorylated ERK 1/2 was evaluated by western blot. No differences were found between the groups. Thus, increased survival does not appear to be mediated by ERK 1/2 activation (AU)

Depression as a Clinical Determinant of Dependence and Low Quality of Life in Elderly Patients with Cardiovascular Disease / Depressão como Determinante Clínico de Dependência e Baixa Qualidade de Vida em Idosos Cardiopatas

Background: The aging process promotes a progressive increase in chronic-degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns “quality of life related to health”. Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists. Objective: Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life. Methods: This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State. Results: The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 ± 6.62 years-old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 ± 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36. Conclusion: Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression. .

Fundamento: Com o envelhecimento, a prevalência de doenças crônico-degenerativas sofreu aumento progressivo. A repercussão dessas doenças sobre a capacidade funcional foi reconhecida. Outro parâmetro de saúde é a “qualidade de vida relacionada à saúde”. Na população idosa, as doenças cardiovasculares destacam-se pelo impacto epidemiológico e clínico. Elas, geralmente, vêm associadas a outras afecções. Esse conjunto de problemas pode comprometer a independência e a qualidade de vida do idoso que busca tratamento cardiológico. Objetivo: Avaliar, em uma população de idosos cardiopatas, quais são os determinantes clínicos mais relevantes de dependência e de qualidade de vida. Métodos: O grupo foi selecionado aleatória e consecutivamente, sendo aplicados quatro questionários: HAQ, SF-36, PRIME‑MD e Mini Exame do Estado Mental. Resultados: Incluiu-se 1020 idosos, 63,3% mulheres. O grupo tinha em média 75,56 ± 6,62 anos. 61,4% mostrou-se independente ou com dependência leve. O escore de qualidade de vida foi elevado (HAQ: 88,66 ± 2,68). 87,8% dos pacientes apresentou escore total do SF-36 ≥ 66. À análise multivariada, a associação entre os diagnósticos e graus elevados de dependência foi significante apenas para acidente vascular cerebral prévio (p = 0,014), obesidade (p < 0,001), sedentarismo (p = 0,016), osteoartrite (p < 0,001), déficit cognitivo (p < 0,001), e depressão maior (p < 0,001). Ao analisarmos a qualidade de vida, a depressão maior e a depressão por doença física associou-se significativamente com todos os domínios do SF-36. Conclusão: Em uma população de idosos cardiopatas, os determinantes clínicos mais relevantes de prejuízos para dependência e qualidade de vida foram as comorbidades não cardiovasculares, particularmente a depressão. .

Actualización en el diagnóstico y manejo del daño hepático agudo grave en el embarazo / Causes and management of severe acute liver damage during pregnancy

Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

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.

Abordagem inicial à insuficiência hepática aguda / Initial approach to acute hepatic insufficiency

A insuficiência hepática aguda é uma entidade clínica rara cujo reconhecimento precoce é crucial para a instituição de medidas e transferência do paciente para centro de transplante hepático emergencial. O objetivo deste artigo é revisar tópicos diagnósticos e o tratamento inicial da insuficiência hepática aguda.

Acute liver failure is a rare critical illness whose early recognition is crucial for the establishment of management measures and to proceed the patient transference to a center with active emergency liver transplantation program. The purpose of this article is to review basic topics of diagnosis and initial treatment of acute liver failure.

Therapeutic effects of blood purification in treatment of fulminant hepatic failure

OBJECTIVES: To evaluate the clinical effects of blood purification for treating fulminant hepatic failure (FHF). METHODS: Thirty-three severe FHF patients with hepatic encephalopathy (HE) above grade III were subjected to a combined blood purification treatment in addition to the comprehensive liver protection therapy. Patients underwent continuous hemofiltration on a daily basis during the daytime followed by sequential treatment with plasma exchange or hemodialysis every 2-3 days. The therapeutic effects of this treatment were evaluated. RESULTS: After treatment with blood purification, restoration of consciousness (those who abandoned the treatment without restoration of consciousness were excluded) was achieved in 6 of 8 cases (75%) in acute liver failure (ALF) group, 3 of 3 cases (100%) in subacute liver failure (SALF) group, and 9 of 14 cases (64.29%) in acute/subacute on chronic liver failure (A/SCLF) group. Of all cases, 11 patients restored consciousness after 7 days in a coma. The rate of long-term survival (those who abandoned the treatment were excluded) was 3/7 (42.86%) for ALF group, 2/2 (100%) for SALF group, and 1/11 (9.09%) for A/SCLF group. The levels of hemoglobin and platelet in peripheral blood were significantly reduced after blood purification. CONCLUSIONS: Treatment of FHF patients with daily continuous hemofiltration during the daytime is effective in treating HE and in improving health status in the early stages of the disease. Long-term prognosis also benefits from this treatment. The rate of consciousness recovery and long-term survival is highest in SALF group followed by ALF group. This treatment is less effective in A/SCLF patients. It should be noted that blood purification procedure may cause damage to blood cells.

Falência hepática aguda / Acute liver failure

Falência hepática aguda é uma síndrome clínica devastadora, com alta taxa de mortalidade, apesar dos recentes avanços da terapia intensiva. Determinar a causa tem importantes implicações prognósticas, e o transplante de fígado é um tratamento que salva vidas em casos selecionados. O conhecimento das últimas diretrizes e protocolos pode levar a melhores resultados.

Acute liver failure is a devasting clinical syndrome, with high mortality rate, despite critical care advances. Determining the cause has important prognostic implications, and the orthotopic liver transplantation is a life-saving treatment in select cases. Knowledge of the latest guidelines and treatment protocols can lead to improved patient case.

Acute liver failure: an update

Acute liver failure is a serious medical emergency resulting from various insults that liver sustains. In our setting, viral etiology is the commonest cause. The syndrome results in significant liver damage leading to hepatic encephalopathy, coagulopathy and several other serious clinical consequences. Sepsis, cardio vascular failure and renal failure can result in multi system organ failure and fatal consequences. Management requires identification of etiologic agent as soon as possible. Nursing care in intensive care unit [ICU] setting is recommended. Attention towards correction of electrolyte imbalance, coagulopathy, encephalopathy and systemic complication along with judicious use of antibiotics help in obtaining a favorable outcome. Transplant remains the ultimate management

Curso de atualização em emergências médicas: aula 18: insuficiência hepatica aguda / Course of updating in medical emergencies: class 18: acute hepatic failure

A insuficiência hepática aguda (IHA) é uma síndrome clínica extremamente grave, de diagnóstico precoce difícil, evolução rápida e alta mortalidade. Nesta revisão buscamos reunir as informações mais atuais sobre classificação, etiologia, diagnóstico e tratamento, discutindo as diversas controvérsias sobre o tema. O diagnóstico da IHA é difícil e engloba o quadro clínico e laboratorial de hepatite aguda (grave), tempo de protrombina alargado, com qualquer alteração do sensório, além de pesquisa cuidadosa na história do paciente, incluindo o uso de medicações ou ervas e presença de diagnóstico prévio de hepatopatia. O diagnóstico etiólogico inclui infecções virais, medicamentos e toxinas, causas cardíacas e vasculares, metabólicas, além da hepatite autoimune, doenças de Wilson e neoplasias. O tratamento da IHA é dado em duas etapas, sendo a primeira constituída pelas medidas de suporte, prevenção e tratamento das complicações, que devem ser oferecidas a todos os pacientes, e a segunda pelas medidas específicas, que serão direcionadas dependendo da etiologia. O transplante hepático é a única terapia definitiva para os pacientes que não conseguem o restabelimento da função hepática.

Acute hepatic failure (AHF) is one extremely serious clinical syndrome of difficult pre-emptive diagnosis, rapid evolution and high mortality. In this review we summarized the current information regarding its classification, etiology, diagnosis and treatment, and discussed the controversies about the issue. The diagnosis of the AHF is difficult and includes laboratorial and clinical findings of severe acute hepatitis, increased prothrombin time and presence of hepatic encephalopathy. It is necessary that a careful history of the patient be obtained especially with respect to utilization of medications, herbs as well as the presence of previous diagnosis of liver disease. The possible etiologies include viral infections, cardiac and vascular affections, medications and toxins, metabolic causes, auto-immune hepatitis, Wilson's disease and neoplasm. The treatment of AHF requires support measures, prevention and treatment of complications that must be offered all patients and specific measures which should be offered according to the etiology of AHF. Liver transplant is the only definitive therapy for patients who do not recover the hepatic function.

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.

Natural course of fulminant hepatic failure: the scenario in Bangladesh and the differences from the west

Fulminant hepatic failure [FHF] is a devastating complication of acute viral hepatitis, leading to death in most cases. The etiology and predictors of outcome differ according to the geographical region. This study was conducted with the aim of evaluating the etiology, complications, and outcome of FHF in Bangladesh. In this prospective study, we included 67 consecutive cases of FHF presenting to the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, between November 2003 and May 2008. Thirty-nine of the patients were male and 28 were female. Data was analyzed using SPSS, version 13.0. The mean age of the subjects was 31.9 +/- 11 .7 years. Hepatitis E virus [HEV] was the commonest etiological factor for FHF [50 cases, 74.6%]; of the 50 cases with HEV infection, 43 [64.2%] were not coinfected with any other virus, four cases were Hepatitis B virus [HBV] carriers, and three had coinfection with hepatitis A virus [HAV]. HBV was the cause of FHF in nine [13.4%] patients. HCV, paracetamol, and alcohol were not responsible for any of the cases. Most of the patients [57 patients, 85%] developed FHF within 2 weeks of the onset of jaundice. Of the 67 patients, 49 [73.1%] died. Cerebral edema was the single most common cause of death [48 patients, 71.6%]. Other complications were renal failure [23 patients, 34.3%], sepsis [15 patients, 22.4%], electrolyte imbalance [12 patients 17.9%], and bleeding tendency [7 patients, 10.4%]. Occurrence of cerebral edema, longer prothrombin time, higher grade of encephalopathy, and longer jaundice-to-encephalopathy interval had significant negative influence on outcome. The etiology of FHF in Bangladesh is different from that in the West. Prolongation of prothrombin time and occurrence of cerebral edema are predictors of the worst prognosis

Disfunção hepática aguda em paciente com hipertireoidismo e hepatite por vírus B: recuperação após plasmaférese e tireoidectomia - relato de caso / Acute hepatic failure in a patient with hyperthyroidism and virus B hepatitis: recovery after plasmapheresis and thyroidectomy - a case report

Paciente masculino, 31 anos, internado com quadro de dor abdominal, náuseas, vômitos, icterícia e febre, iniciado há duas semanas. História de hipertireoidismo e tratamento irregular com propiltiuracil há dois anos, interrompeu a medicação quando iniciou o quadro atual. Apresentava bócio difuso, cerca de 120 g, T4L 22,7 ng/dL (VN 0,8-1,9 ng/dL); TSH < 0,002 µUI/mL (VN 0,4-5 µUI/mL). Transaminases, bilirrubinas total e direta séricas elevadas. Foi mantido sem antitireoidiano e iniciado propranolol até a dose de 480 mg/dia. Ultra-sonografia de abdome foi normal e sorologias para hepatites A, B e C indicaram infecção aguda por vírus B. Ocorreu piora da função hepática e manutenção de níveis elevados de hormônios tireoidianos. Visando evitar necessidade futura de antitireoidiano, obter rápida normalização dos níveis de hormônios tireoidianos e em virtude do tamanho do bócio foi indicado tireoidectomia. O paciente foi submetido a uma sessão de plasmaférese terapêutica, imediatamente antes da cirurgia, e tireoidectomia subtotal sem intercorrências. No quinto dia após a cirurgia, o paciente apresentava melhora da função hepática e baixos níveis séricos de T4 livre. Concluímos que o hipertireoidismo prévio pode exacerbar e perpetuar a disfunção hepática causada por hepatite viral aguda e que a plasmaférese é um meio rápido, seguro e eficaz de reduzir os níveis de hormônio tireoidiano, permitindo uma tireoidectomia bem-sucedida em pacientes com tireotoxicose grave.

A 31-year-old man admitted with abdominal pain, nauseas, vomiting, jaundice and fever that had began 2 weeks before. He had a history of hyperthyroidism and an irregular treatment with propylthiouracil (PTU) for 2 years. He had stopped PTU when the current symptoms started. The patient presented diffuse goiter, about 120g, FT4 22.7 ng/dL (N: 0.8 - 1.9 ng/dL); THS < 0.002 µUI/mL (N 0.4-5 µUI/mL). Transaminases, serum total and direct bilirubins were increased. He was kept without PTU and propranolol was started and increased until the dose of 480 mg/day. Abdominal ultrassonography was normal and serologic markers for hepatitis A, B and C pointed to acute virus B hepatitis. The patient presented a worse of hepatic function and elevated thyroid hormones levels. To avoid the future need of antithyroid drugs, to get a fast normalization of thyroid hormones levels and because of the goiter size thyroidectomy was recommended. The patient underwent one therapeutic plasmapheresis session just before the surgery. A total thyroidectomy was performed without complications. At the 5th day after surgery the patient presented improvement of hepatic function and low FT4 serum levels. We concluded that preexisting hyperthyroidism may aggravate or perpetuate a hepatic failure caused for acute viral hepatitis and plasmapheresis is a rapid, reliable and effective way to lower thyroid hormones serum levels, allowing a successful thyroidectomy in patients with severe thyrotoxicosis.