Fulminant acute hepatitis in pediatrics in Latin America and the Caribbean

SUMMARY OBJECTIVE: The objective of this review was to investigate the epidemiology of Fulminant Acute Hepatitis in Latin America and the Caribbean and identify possible measures aimed at a better understanding and improvement of patient support. METHODS: We used 3 different researchers to investigate the topic of Fulminant Acute Hepatitis in pediatrics in papers published by Latin American and Caribbean authors in the PubMed and SciELO databases from 2000 to 2016. RESULTS: We found 2,879 articles in the databases searched. After selecting and excluding articles according to the study protocol, 68 remaining studies were obtained for analysis. A total of 1,265 cases of acute fulminant hepatitis were detected, with a predominance of females (42.9%), followed by males (39.4%), with no description of sex in 17.7% of the cases. The main cause was viral hepatitis, representing 45.1% of the cases. The hepatitis A virus was responsible for 34.7% of the total cases and 76.9% of the infectious causes. Of the total number of patients, 26.9% were described as idiopathic, and 11.5% had no cause. CONCLUSION: The preventable causes of Fulminant Acute Hepatitis include hepatitis viruses - primarily the hepatitis A virus - and poisoning. Active vaccination, basic sanitation, and public awareness can reduce the number of patients and, consequently, the costs of liver transplantation due to these causes.

RESUMO OBJETIVO: O objetivo desta revisão foi investigar a epidemiologia da hepatite aguda fulminante na América Latina e Caribe e identificar possíveis ações objetivando melhor compreensão e melhora do suporte desses pacientes. MÉTODOS: Pesquisou-se o tema hepatite aguda fulminante em pediatria, publicado por autores da América Latina e Caribe nas bases de dados PubMed e SciELO por três diferentes investigadores no período de 2000 a 2016. RESULTADOS: Foram encontrados 2.879 artigos nos bancos de dados pesquisados. Após seleção e exclusão de artigos de acordo com o protocolo de pesquisa, resultaram 68 estudos remanescentes para análise. Foram avaliados 1.265 casos com hepatite aguda fulminante, havendo predominância no sexo feminino (42,9%), seguido do masculino (39,4%), sendo que não houve a descrição de sexo em 17,7% dos casos. A principal causa foram as hepatites virais (HV), representando 45,1% dos casos. O vírus da hepatite A foi responsável por 34,7% do total de casos e por 76,9% das causas infecciosas. Do total de pacientes, 26,9% foram descritos como idiopáticos e 11,5% não tiveram causa descrita. CONCLUSÃO: As causas evitáveis de hepatite aguda fulminante incluem os vírus da hepatite — principalmente o vírus da hepatite A — e intoxicações. A vacinação ativa, o saneamento básico e a conscientização pública podem reduzir o número de doentes e, consequentemente, os custos com transplante hepático por essas causas.

Manejo de la hepatitis B aguda grave y fulminante / Management of acute fulminant hepatitis B

Fulminant hepatitis B virus infection occurs in less than 1percent of acutely infected patients. Acute hepatitis Baccounts for 2-42 percent of the total of fulminant hepatitis cases depending on the geographic area. This infection is associated with 65-93 percent of mortality, without liver transplantation. Its pathogenesis is related to a severe immune response to infected hepatocytes, causing massive cytolysis and liver failure. During the last 3 decades its prognosis has improved due to better medical support in intensive care units, the use of liver transplantation and an improvement in the prevention and management of its complications. More recently the use of liver support devices (MARS, Prometheus, and BAL) has been considered in this situation as a bridge to liver transplantation. Recurrent hepatitis B virus reinfection of the graft was a major issue in the past, but currently with the use of hepatitis B immunoglobulin (HBIg) and oral antiviral therapy, the prognosis has improved, leading to excellent graft and patient outcomes after liver transplantation. There is controversial data on the use of oral antiviral therapy among fulminant hepatitis patients. While some authors have shown beneficial effects, other communications have failed to demonstrate any benefits. Nevertheless, many experts currently recommend the use of oral antiviral therapy in this setting due to their relative safety and potential benefits. This paper reviews the current view on management issues in reference to the patient with fulminant hepatic failure due to acute hepatitis B.

La hepatitis fulminante por virus de hepatitis B ocurre en menos del 1 por ciento de los casos de hepatitis B aguda. Del total de hepatitis fulminantes, entre el 2-42 por ciento son causadas por hepatitis B aguda, dependiendo del lugar geográfico donde se estudia. Se asocia a elevada mortalidad, entre 65-93 por ciento, sin el uso de trasplante hepático. Su patogenia se relaciona a una significativa respuesta inmune a hepatocitos infectados, determinando citolisis masiva y falla hepática. En las últimas 3 décadas el pronóstico de esta patología ha mejorado gracias al soporte médico en unidades de tratamiento intensivo, a la implementación del trasplante hepático, y a la mejoría en la prevención y manejo de sus complicaciones. Más recientemente se ha usado dispositivos de soporte hepático (MARS, Prometheus, BAL), como un puente al trasplante hepático. La reinfección del injerto con hepatitis B era una consideración importante en el pasado, pero con el uso de gamaglobulina específica para hepatitis B y el tratamiento antiviral oral, su pronóstico ha mejorado, determinando un excelente pronóstico del injerto y del paciente a largo plazo post trasplante hepático. Existen datos controversiales referentes al uso de antivirales orales durante una hepatitis fulminante, pues algunos autores muestran beneficios en esta condición, pero otros no han demostrado un beneficio real. Sin embargo, muchos expertos actualmente recomiendan su uso en este escenario, pues son seguros y pueden tener un potencial beneficio. Este artículo revisa el manejo actual del paciente con hepatitis fulminante por hepatitis B aguda.

Factors influencing the severity of acute viral hepatitis A / 대한간학회지

BACKGROUND/AIMS: Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. METHODS: We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR> or =1.5). Clinical variables were compared between the two groups. RESULTS: The incidence of fulminant hepatitis was 1.4 % (10/713) in patients with acute hepatitis A. Thirty-three (4.6 %) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. CONCLUSIONS: While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection. (

HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in cirrhotics in Bangladesh. Sewerage contamination of piped water following floods may contribute to the higher incidence of HEV infection.

Hepatotropic viruses in the Brazilian Amazon: a health threat: [review]

Viral Hepatitis B, C and D are a serious public health problem in Brazil and other South American countries, mainly in the Amazonian region. Despite the paucity of clinical and epidemiological studies, a high prevalence of Hepatitis viruses has often been described in this area. Genotype F of Hepatitis B and Genotype III of Hepatitis D have been found to be quite prevalent in this area and preliminary studies have implicated both genotypes in carcinogenesis and peculiar pathogenic liver mechanisms. Initial epidemiological studies have further demonstrated a high prevalence of Hepatitis C in the western Brazilian Amazon. The geographic, cultural, ethnic and environmental aspects of this region may favor hepatotropic virus dissemination, as well as rendering difficult the implementation of governmental programs in the treatment of patients and prevention of disease dissemination.

Acetaminophen overdose in Jamaica / Sobredosis de acetaminofén en Jamaica

Acetaminophen is a dose dependent hepatotoxin which is frequently associated with intentional self-harm. Forty-nine cases of parasuicide attempts involving paracetamol only or in combination with another drug were treated at the UHWI, Jamaica, between 1994-2004. The majority were women (84%) and the mean age was 23 years. Acetaminophen was the only agent ingested in 71% of cases; 29% involved an additional drug. Patients presented an average of 6.5 hours after ingestion (range 1-45 hours). Serum transaminases were elevated in 18% of cases and N-acetylcysteine (NAC) therapy given in 55%. The mean duration of hospitalization was three days. One patient developed liver failure and there were no deaths. Education of the public and medical profession is needed to increase awareness of the potential toxic effects of acetaminophen overdose. N-acetylcysteine therapy should be given early in suspected cases.

El acetaminofén es una hepatotoxina dosis-dependiente, frecuentemente asociada con intenciones auto-destructivas. Cuarenta y nueve casos de intentos parasuicidas que involucraban paracetamol o combinación con otra droga, fueron tratados en el UHWI, Jamaica, entre 1994-2004. En la mayoría de los casos se trataba de mujeres (84%) y la edad promedio fue 23 años. El acetaminofén fue el único agente ingerido en 71% de los casos; 29% involucraron un medicamento adicional. Las transaminasas en suero fueron elevadas en 18% de los casos y se aplicó terapia de N-acetilcisteína en el 55% de los casos. La duración promedio de hospitalización fue de tres días. Uno de los pacientes tuvo un fallo hepático y no hubo muertes. Se requiere la educación del público y la profesión médica a fin de aumentar la conciencia sobre los efectos tóxicos potenciales de la sobredosis de acetaminofén. La terapia con N-acetilcisteína (NAC) debe aplicarse tan pronto como el caso despierte sospecha.

Occurrence & nucleotide sequence analysis of hepatitis G virus in patients with acute viral hepatitis & fulminant hepatitis.

BACKGROUND & OBJECTIVE: Association of hepatitis G virus (HGV) with acute viral hepatitis (AVH) and fulminant hepatitis (FH) is not clearly understood.This study was designed to asses the occurrence of HGV infection and its relationship with other hepatotropic viruses in patients with FH and AVH and also to determine the nucleotide sequence of HGV isolates. METHODS: The study included 100 patients of FH and 125 of AVH on the basis of clinical examination, liver function test and serology for hepatitis A, B, C and E virus. HGV RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing for 4 randomly selected samples followed by phylogenetic analysis. RESULTS: Of the 100 patients with FH, 30 were negative for hepatitis viruses A, B, C and E by serology (non A-non E) while 60 were negative in the AVH group. In the non A-non-E hepatitis group, HGV was positive in 16.66 per cent (5/30) cases of FH, 10 per cent (6/60) cases of AVH and 6 per cent (6/100) of healthy controls. The difference in HGV seropositivity between FH and AVH patients was statistically not significant compared to healthy controls, while HBV and HCV infections were significant. The four isolates sequenced seemed to be of same type and close to Chinese strain of HGV (Y13755.1 Y13756.1 Y15407, and U67782) on phylogeny. INTERPRETATION & CONCLUSION: In HGV infection was not found to be clinically significant as well as nonpathogenic in the patients of FH and AVH and appeared to be an innocent bystander in the course of the disease. The four sequenced HGV isolates showed close pairing with Chinese strains.

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

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

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

Incidence and Risk Factors of Acute Hepatic Failure after Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma / 대한소화기학회지

BACKGROUND/AIMS: Although transcatheter arterial chemoembolization (TACE) is a major treatment modality for unresectable hepatocellular carcinoma (HCC), acute hepatic failure after TACE is not rare. However, reports dealing with this important complication are not good enough and results are often variable. The purpose of this study was to evaluate the incidence and associated risk factors of acute hepatic failure after TACE. METHODS: From January 2001 to November 2004, six hundred and thirtytwo TACE sessions were performed in 377 patients (294 men and 83 women). Adriamycin mixed lipiodol solution and gelfoam were used for TACE. Various clinical and radiological factors before and after the procedure were reviewed retrospectively. Univariate and multivariate analyses were performed to evaluate the risk factors associated with the development of acute hepatic failure after TACE. RESULTS: Acute hepatic failure occurred in 76 (12.0%) of the 632 TACE sessions within 14 days. Univariate analysis revealed that Child-Pugh class, 1st TACE, total bilirubin level, number of involved segments, total size of tumor, presence of right portal vein thrombosis (PVT) or main PVT, involvement of segment 1, 5, 6, 7, modified UICC stage, and doses of chemotherapeutic agent were significantly different between the patients with or without hepatic failure after TACE. Among them, elevated total bilirubin (p=0.001, E (beta)=1.449), presence of right (p=0.035, E (beta)=2.109) or main (p=0.011, E (beta)=4.067) PVT were independently associated factors in multivariate analysis. CONCLUSIONS: The incidence of acute hepatic failure after TACE was 12.0%. Elevated bilirubin level and portal vein thrombosis could be considered as the predictive factors for acute hepatic failure after TACE in HCC patients.

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

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

Insuficiência hepática aguda da gravidez: experiência clínica com sete casos / Acute liver failure of pregnancy: clinical experience with seven cases

Objetivos: avaliar a dificuldade diagnóstica, o tratamento e seu resultado em casos de insuficiência hepática aguda da gravidez. Métodos: sete pacientes com insuficiência hepática aguda da gravidez admitidas em nosso Serviço nos últimos quatro anos foram estudadas com ênfase nos sintomas presentes, achados laboratoriais, curso clínico, complicaçöes maternas e sobrevida fetal. Resultados: a média de idade foi de 25,8 anos (sendo duas primigestas) com idade gestacional média de 30,1. Destas, quatro receberam diagnóstico final de esteatose hepática aguda da gravidez e três de colestase intra-hepática da gravidez. Os principais sinais e sintomas encontrados foram: anorexia, náusea, dor abdominal, icterícia e encefalopatia. Ocorreu morte materna em dois casos: uma paciente por falência hepática enquanto aguardava órgäo para transplante e outra por falência hepática, coagulopatia grave e choque hemorrágico após biopsia hepática. Uma paciente com esteatose hepática aguda evoluiu para cronicidade e encontra-se viva um ano após transplante hepático. Nos quatro casos restantes houve completa remissäo do quadro com as medidas de suporte, associadas à interrupçäo da gravidez. As mortalidades materna e fetal foram, respectivamente, 28,6 por cento e 57,1 por cento. Conclusöes: conclui-se, nesta experiência inicial, que a insuficiência hepática aguda da gravidez constitui evento clínico grave, de elevada mortalidade materno-fetal, e que seu pronto reconhecimento e encaminhamento para centros terciários especializados em fígado, além da imediata interrupçäo da gestaçäo, säo fatores decisivos para o sucesso do tratamento.

Pronóstico vital en insuficiencia hepática aguda grave: valor de los índices cuantitativos de evaluación / Life prognosis in severe acute hepatic failure: value of assessment quantitative index

The aim of this study was to assess the predictive value for mortality of admission and daily APACHE II score, mortality due to multiple organ failure and the organ failure score in patients with acute hepatic failure. We retrospectively studied 15 such patients admitted to an intensive care unit. Thirteen patients died (87 percent) and their admission APACHE II score was 22ñ7.5 compared to 21ñ8.5 in survovors. Daily APACHE II score, mortality due to multiple organ failure and multiple organ failure score had a 100 percent sensitivity to predict mortality and a 69.2, 76.9 and 76.9 percent specificity respectively. The predictive accuracies of multiple organ failure and multiple organ failure score were 80 percent and significantly better than the accuracy of admission APACHE II score (53 percent). We conclude that these prognostic scores can be useful in the assessment of patients with acute hepatic failure