RESUMO
OBJECTIVE: To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years. STUDY DESIGN: We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021. RESULTS: Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively. CONCLUSIONS: The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.
Assuntos
Infecções por Adenoviridae , COVID-19 , Hepatite , Humanos , Criança , Adenoviridae , Estudos Retrospectivos , Incidência , Infecções por Adenoviridae/epidemiologiaRESUMO
OBJECTIVE: To determine predictors of native liver survival (NLS) in children and adolescents with autoimmune hepatitis (AIH). STUDY DESIGN: The medical records of children and adolescents with AIH were reviewed. A questionnaire was used to collect data on clinical presentation, biochemical and histologic findings, and treatment. RESULTS: A total of 819 patients were included, 89.6% with AIH-1 and 10.4% with AIH-2. The median age (months) at onset was 108 (min 6; max 210; IQR 59). The female sex was predominant (75.8%). The overall survival was 93.0%, with an NLS of 89.9%; 4.6% underwent liver transplantation. The risk of death or liver transplantation during follow-up was 3.2 times greater in patients with AIH-1 (P = .024). Greater levels of aspartate aminotransferase, alanine aminotransferase, serum albumin, platelet, and normal international normalized ratio at the initial presentation were associated with longer NLS (P = .046, P = .006, P < .001, P = .001, and P = .019, respectively). Normal C3 levels was associated with longer NLS (P = .017), with a chance of death or liver transplantation during follow-up being 3.4 times greater in patients with C3 below normal. Death or liver transplantation during follow-up was 2.8 times greater in patients with associated sclerosing cholangitis (P = .046). Complete remission favored NLS (P < .001), with a risk of death or liver transplantation 11.7 times greater for patients not achieving remission. CONCLUSIONS: The best predictors of NLS in children and adolescents with AIH were the AIH-2 subtype, a normal C3 at diagnosis, remission during treatment, and normal a cholangiogram during the disease course.
Assuntos
Hepatite Autoimune/mortalidade , Hepatite Autoimune/terapia , Transplante de Fígado/estatística & dados numéricos , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Criança , Pré-Escolar , Colagogos e Coleréticos/uso terapêutico , Colangite Esclerosante/complicações , Colangite Esclerosante/tratamento farmacológico , Complemento C3 , Feminino , Hepatite Autoimune/classificação , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunossupressores/uso terapêutico , Lactente , Coeficiente Internacional Normatizado , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Indução de Remissão , Albumina Sérica , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
OBJECTIVES: The aim of the study was to assess neurodevelopmental outcomes among children with biliary atresia (BA) surviving with their native liver at ages 3 to 12 years and evaluate variables that associate with neurodevelopment. METHODS: Participants (ages 3-12 years) in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with Weschler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III, ages 3-5 years) and Weschler Intelligence Scale for Children, 4th edition (WISC-IV, ages 6-12 years). Continuous scores were analyzed using Kolmogorov-Smironov tests compared with a normal distribution (meanâ=â100â±â15). Effect of covariates on Full-Scale Intelligence Quotient (FSIQ) was analyzed using linear regression. RESULTS: Ninety-three participants completed 164 WPPSI-III (mean age 3.9) and 51 WISC-IV (mean age 6.9) tests. WPPSI-III FSIQ (104â±â14, Pâ<â0.02), Verbal IQ (106â±â14, Pâ<â0.001), and General Language Composite (107â±â16, Pâ<â0.001) distributions were shifted higher compared with test norms. WISC-IV FSIQ (105â±â12, Pâ<â0.01), Perceptual Reasoning Index (107â±â12, Pâ<â0.01), and Processing Speed Index (105â±â10, Pâ<â0.02) also shifted upwards. In univariate and multivariable analysis, parent education (Pâ<â0.01) was a significant predictor of FSIQ on WPPSI-III and positively associated with WISC-IV FSIQ. Male sex and higher total bilirubin and gamma glutamyl transferase (GGT) predicted lower WPPSI-III FSIQ. Portal hypertension was predictive of lower WISC-IV FSIQ. CONCLUSIONS: This cohort of children with BA and native liver did not demonstrate higher prevalence of neurodevelopmental delays. Markers of advanced liver disease (higher total bilirubin and GGT for age ≤5 years; portal hypertension for age ≥6) correlate with lower FSIQ and may identify a vulnerable subset of patients who would benefit from intervention.
Assuntos
Atresia Biliar/psicologia , Transtornos do Neurodesenvolvimento/epidemiologia , Atresia Biliar/sangue , Atresia Biliar/patologia , Bilirrubina/sangue , Criança , Desenvolvimento Infantil , Pré-Escolar , Escolaridade , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/psicologia , Fígado/patologia , Estudos Longitudinais , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Escalas de Wechsler , gama-Glutamiltransferase/sangueRESUMO
OBJECTIVE: To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis. STUDY DESIGN: Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis. Median 2D (8) and point (10) shear wave speed measurements were calculated for each subject and used for analyses. The Mann-Whitney U test was used to compare shear wave speed and laboratory measurements between patients with and without biliary atresia. Receiver operating characteristic curve analyses and multivariable logistic regression were used to evaluate diagnostic performance. RESULTS: Thirteen subjects (31.7%) were diagnosed with biliary atresia, and 28 subjects (68.3%) were diagnosed with other causes of neonatal cholestasis. Median age at the time of ultrasound SWE was 37 days. Median 2D (2.08 vs 1.49 m/s, P = .0001) and point (1.95 vs 1.21 m/s, P = .0014) ultrasound SWE measurements were significantly different between subjects with and without biliary atresia. Using a cut-off value of >1.84 m/s, 2D ultrasound SWE had a sensitivity = 92.3%, specificity = 78.6%, and area under the receiver operating characteristic curve (AuROC) of 0.89 (P < .0001). Using a cut-off value of >320 (U/L), gamma-glutamyl transferase (GGT) had a sensitivity = 100.0%, specificity = 77.8%, and AuROC of 0.85 (P < .0001). Multivariable logistic regression demonstrated an AuROC of 0.93 (P < .0001), with 2 significant covariates (2D ultrasound SWE [OR = 23.06, P = .01]; GGT [OR = 1.003, P = .036]). CONCLUSIONS: Ultrasound SWE and GGT can help discriminate biliary atresia from other causes of neonatal cholestasis.
Assuntos
Atresia Biliar/diagnóstico por imagem , Colestase/diagnóstico por imagem , Alanina Transaminase/sangue , Atresia Biliar/patologia , Biomarcadores/sangue , Colestase/etiologia , Colestase/patologia , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Ultrassonografia , gama-Glutamiltransferase/sangueRESUMO
OBJECTIVES: Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1âg/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5âmg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; Pâ>â0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.
Assuntos
Atresia Biliar/cirurgia , Imunoglobulinas Intravenosas/uso terapêutico , Atresia Biliar/mortalidade , Pré-Escolar , Drenagem , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Recém-Nascido , Transplante de Fígado , Masculino , Portoenterostomia Hepática , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the impact of corticosteroid therapy on the growth of participants in the Steroids in Biliary Atresia Randomized Trial (START) conducted through the Childhood Liver Disease Research Network. The primary analysis in START indicated that steroids did not have a beneficial effect on drainage in a cohort of infants with biliary atresia. We hypothesized that steroids would have a detrimental effect on growth in these infants. STUDY DESIGN: A total of 140 infants were enrolled in START, with 70 randomized to each treatment arm: steroid and placebo. Length, weight, and head circumference were obtained at baseline and follow-up visits to 24 months of age. RESULTS: Patients treated with steroids had significantly lower length and head circumference z scores during the first 3 months post-hepatoportoenterostomy (HPE), and significantly lower weight until 12 months. Growth trajectories in the steroid and placebo arms differed significantly for length (P < .0001), weight (P = .009), and head circumference (P < .0001) with the largest impact noted for those with successful HPE. Growth trajectory for head circumference was significantly lower in patients treated with steroids irrespective of HPE status, but recovered during the second 6 months of life. CONCLUSIONS: Steroid therapy following HPE in patients with biliary atresia is associated with impaired length, weight, and head circumference growth trajectories for at least 6 months post-HPE, especially impacting infants with successful bile drainage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00294684.
Assuntos
Corticosteroides/efeitos adversos , Atresia Biliar/tratamento farmacológico , Atresia Biliar/cirurgia , Insuficiência de Crescimento/induzido quimicamente , Sarcopenia/induzido quimicamente , Corticosteroides/uso terapêutico , Atresia Biliar/mortalidade , Peso Corporal/efeitos dos fármacos , Cefalometria/métodos , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Método Duplo-Cego , Insuficiência de Crescimento/epidemiologia , Insuficiência de Crescimento/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Monitorização Fisiológica/métodos , Portoenterostomia Hepática/métodos , Portoenterostomia Hepática/mortalidade , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Valores de Referência , Medição de Risco , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. STUDY DESIGN: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. RESULTS: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P < .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P < .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age. CONCLUSION: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00061828 and NCT00294684.
Assuntos
Atresia Biliar/terapia , Deficiências do Desenvolvimento/etiologia , Fígado/fisiologia , Testes Neuropsicológicos , Atresia Biliar/complicações , Pré-Escolar , Cognição , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Destreza Motora , Análise Multivariada , Estudos Observacionais como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Risco , Resultado do Tratamento , Populações VulneráveisRESUMO
OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 µM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00061828 and NCT00294684.
Assuntos
Atresia Biliar/cirurgia , Bilirrubina/sangue , Progressão da Doença , Portoenterostomia Hepática , Ascite/epidemiologia , Atresia Biliar/epidemiologia , Biomarcadores/sangue , Canadá/epidemiologia , Pré-Escolar , Bases de Dados Factuais , Coagulação Intravascular Disseminada/epidemiologia , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Hipoalbuminemia/epidemiologia , Lactente , Recém-Nascido , Transplante de Fígado/estatística & dados numéricos , Modelos Logísticos , Prognóstico , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The discovery of genetic mutations in children with inherited syndromes of intrahepatic cholestasis allows for diagnostic specificity despite similar clinical phenotypes. Here, we aimed to determine whether mutation screening of target genes could assign a molecular diagnosis in children with idiopathic cholestasis. PATIENTS AND METHODS: DNA samples were obtained from 51 subjects with cholestasis of undefined etiology and surveyed for mutations in the genes SERPINA1, JAG1, ATP8B1, ABCB11, and ABCB4 by a high-throughput gene chip. Then, the sequence readouts for all 5 genes were analyzed for mutations and correlated with clinical phenotypes. Healthy subjects served as controls. RESULTS: Sequence analysis of the genes identified 14 (or 27%) subjects with missense, nonsense, deletion, and splice site variants associated with disease phenotypes based on the type of mutation and/or biallelic involvement in the JAG1, ATP8B1, ABCB11, or ABCB4 genes. These patients had no syndromic features and could not be differentiated by biochemical markers or histopathology. Among the remaining subjects, 10 (or â¼20%) had sequence variants in ATP8B1 or ABCB11 that involved only 1 allele, 8 had variants not likely to be associated with disease phenotypes, and 19 had no variants that changed amino acid composition. CONCLUSIONS: Gene sequence analysis assigned a molecular diagnosis in 27% of subjects with idiopathic cholestasis based on the presence of variants likely to cause disease phenotypes.
Assuntos
Colestase/genética , Mutação/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Adenosina Trifosfatases/genética , Adolescente , Proteínas de Ligação ao Cálcio/genética , Criança , Pré-Escolar , Colestase/diagnóstico , Diagnóstico Diferencial , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteína Jagged-1 , Proteínas de Membrana/genética , Proteínas Serrate-Jagged , alfa 1-Antitripsina/genéticaRESUMO
Inherited syndromes of intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the prime indication for liver transplantation in children. Our understanding of the pathogenesis of these diseases has increased substantially by the discovery of genetic mutations in children with intrahepatic cholestasis and the findings that inflammatory circuits are operative at the time of diagnosis of biliary atresia. Building on this solid foundation, recent studies provide new insight into genotype-phenotype relationships and how mutations produce altered bile composition and cholestasis. New evidence exists that although liver transplantation is curative for patients with end-stage liver disease owing to cholestasis, some patients may develop recurrence of cholestasis because of the emergence of autoantibodies that disrupt canalicular function in the new graft. Progress is also evident in biliary atresia, with recent studies identifying candidate modifier genes and directly implicating lymphocytes and inflammatory signals in the pathogenesis of bile duct injury and obstruction.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Transportadores de Cassetes de Ligação de ATP , Adenosina Trifosfatases/deficiência , Atresia Biliar/genética , Colestase Intra-Hepática/genética , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Atresia Biliar/patologia , Humanos , Recém-Nascido , Mutação , Fenótipo , Polimorfismo Genético , Tripsina/deficiênciaRESUMO
OBJECTIVE: To provide an updated review on extrahepatic biliary atresia, focusing mainly on its etiopathogenesis, diagnosis, treatment and prognosis. SOURCES: MEDLINE and PubMed databases were searched using the following keywords: biliary atresia, etiopathogenesis, diagnosis, treatment, prognosis, children. SUMMARY OF THE FINDINGS: Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. CONCLUSIONS: Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.
Assuntos
Atresia Biliar , Atresia Biliar/diagnóstico , Atresia Biliar/etiologia , Atresia Biliar/terapia , Criança , Previsões , Humanos , Transplante de Fígado , Portoenterostomia Hepática , PrognósticoRESUMO
OBJETIVOS: Apresentar uma revisão atualizada sobre atresia das vias biliares extra-hepáticas, com ênfase em etiopatogenia, abordagens diagnósticas e terapêuticas e prognóstico. FONTES DOS DADOS: Foram selecionadas pelos sites de busca médica (MEDLINE e PubMed) pesquisas relacionadas à atresia biliar, utilizando as seguintes palavras-chave: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SíNTESE DOS DADOS A atresia das vias biliares extra-hepáticas é a principal indicação de transplante hepático na faixa etária pediátrica. Quanto à etiologia, o citomegalovírus, o reovírus e o rotavírus têm sido os agentes mais estudados como possíveis desencadeadores da obstrução imunomediada da árvore biliar. A resposta imune, especialmente o predomínio da resposta TH1 e do interferon gama, a susceptibilidade genética e as alterações do desenvolvimento embrionário da árvore biliar são aspectos que podem participar na etiopatogênese da obliteração das vias biliares extra-hepáticas. Ainda hoje, o único tratamento disponível é a portoenterostomia, cujos resultados são melhores quando realizada nos primeiros 2 meses de vida. Em relação ao prognóstico, as crianças não tratadas vão a óbito na totalidade, por complicações relacionadas à hipertensão portal e à cirrose hepática, e mesmo os casos tratados necessitam, em sua maioria, do transplante hepático. CONCLUSÃO: A atresia das vias biliares extra-hepáticas continua sendo a principal indicação de transplante hepático em crianças, e a mudança deste panorama depende de um melhor entendimento da etiopatogenia da obstrução biliar nos diferentes fenótipos da doença. Investigações futuras a respeito do papel do interferon gama e de outras citocinas são necessárias para avaliar se esses aspectos seriam potenciais alvos de intervenção terapêutica.
OBJECTIVE: To provide an updated review on extrahepatic biliary atresia, focusing mainly on its etiopathogenesis, diagnosis, treatment and prognosis. SOURCES: MEDLINE and PubMed databases were searched using the following keywords: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SUMMARY OF THE FINDINGS: Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. CONCLUSIONS: Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.