Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, which primarily affects middle-aged women. The liver histology is characterized by inflammation and destruction of the intrahepatic bile ducts as well as a high frequency of granuloma. Although the etiology is unknown, the occurrence of associated multiorganic abnormalities such as Sjogren's syndrome, scleroderma, rheumatic disorders and thyroid gland diseases have been cited as evidence favouring an autoimmune background. Addison and Gull in 1851 described the first patient with jaundice and xanthomatosis. PBC was first mentioned in 1876 as an entity by Hanot. PBC was considered to be a rare disease until in 1973 Sherlock and Scheuer described 100 patients. Since then a greater awareness of the disease combined with a wider use of laboratory screening methods has led to the discovery of an increasing number of patients with PBC. In an epidemiological investigation of PBC in the northern part of Sweden a point prevalence of 151 per 106 was found, which is the highest so far reported, and the mean annual incidence amounted to 13.3 per 106. Asymptomatic PBC was present in more than one third of the patients which is consistent with the finding in other epidemiological investigations and is supposed to explain the higher prevalence of PBC and the better prognosis. Nevertheless 25 patients died during the study period, 14 as a direct consequence of the liver disease. Chronic intrahepatic cholestasis has been reported in sarcoidosis and, moreover, a high frequency of liver granuloma is found. The implication of the present study is that a negative Kveim test in combination with positive mitochondrial antibodies is accurate in differentiating PBC from sarcoidosis. Multisystem involvement is frequently observed in PBC and the present study confirms this. In the prospective investigation of 26 PBC patients 50 % had arthropathy considered to be associated with PBC. Rheumatoid arthritis was found in 5 patients, who all had symptoms of liver disease in addition. Lung function impairment was present in 56% (1 asymptomatic PBC). Most commonly a reduced diffusion capacity was found (36%). Bronchial asthma was present in three patients, and severe lung emphysema in one. Features of Sjogren's syndrome was found in 73% (3 asymptomatic PBC). In 6 patients keratoconjunctivitis sicca (KCS) was evident with the rose bengal test demonstrating corneal staining and a Schirmer test of less than 5 mm. Radiological findings of sialectasia were demonstrated in 6 patients, of whom 5 had KCS as well. The ultimate treatment in PBC is liver transplantation and to calculate the need for that, good epidemiological surveys are needed, and also indicators of hepatocellular function. The present investigation indicates that determination of the von Willebrand factor could be used for this purpose. / <p>Härtill 6 uppsatser</p> / digitalisering@umu

Os estuários são o receptáculo final de muitos contaminantes antrópicos, como os hidrocarbonetos policíclicos aromáticos (HPAs), que podem ser tóxicos aos organismos. A biodisponibilidade dos HPAs pode ser avaliada através de biomarcadores de exposição, como os metabólitos biliares. Este trabalho teve como objetivo avaliar a biodisponibilidade do HPAs em peixes da espécie Mugil curema do Estuário de Santos e de Cananéia, através da análise de metabólitos de HPAs em bile de peixes. As coletas no Estuário de Cananéia foram realizadas nos meses de junho e novembro de 2008 e as coletas no Estuário de Santos foram realizadas entre os meses de março e maio de 2009. Os metabólitos foram analisados através de cromatografia líquida com detector de fluorescência (HPLC/F). A concentração de metabólitos biliares totais para o Estuário de Cananéia variou entre 0,91 a 89,97 ?g g-1 de bile, e para o Estuário de Santos variou de 4,68 a 528,43 ?g g-1 de bile. Houve diferença significativa entre os locais estudados. Observou-se também que não houve diferença significativa entre as amostras de machos e de fêmeas. A biodisponibilidade de HPAs foi considerada como baixa para o Estuário de Cananéia e alta para o Estuário de Santos. Valores de referência foram propostos para analise ambiental de metabólitos biliares de HPAs, sendo estipulada uma concentração de 2,22 ?g g-1 de bile para locais não contaminados. / Estuaries are the final receptacle to many anthropic contaminants, such as polycyclic aromatic hydrocarbons (PAHs), who can be toxic to organisms. The PAH bioavailability can be evaluated through biomarkers, such as biliary metabolites. This work had as objective evaluate the PAHs bioavailability in fishes of Mugil curema from Santos and Cananéia Estuaries, through the analysis of PAHs metabolites in fish bile. The Cananéia Estuary sampling was made in June and November from 2008 and the Santos Estuary sampling was made between the months of March and May from 2009. The metabolites were analyzed through a high performance liquid chromatograph with fluorescence detector (HPLC/F). The biliary metabolites concentrations from the Cananéia Estuary varied between 0,91 a 89,97 ?g g-1 of bile, and from Santos Estuary varied between 4,68 a 528,43 ?g g-1 of bile. There were significant differences between the sampling sites. There were no significant differences between the male and female samples. The PAHs bioavailability was considered low to Cananéia Estuary and high to Santos Estuary. Reference values were proposed to PAHs biliary metabolites environmental analysis, been stipulated a concentration of 2,22 ?g g-1 of bile to uncontaminated sites.

Ambientes marinhos adjacentes a centros urbanos, como a Baía de Santos, estão sujeitos à introdução de contaminantes que apresentam caráter tóxico, como os hidrocarbonetos policíclicos aromáticos (PAHs). A biodisponibilidade dos PAHs pode ser avaliada através de biomarcadores de exposição, como metabólitos biliares e atividade da 7-etoxiresorufina-desetilase (EROD). Este trabalho investigou a biodisponibilidade dos PAHs na Baía de Santos através dos metabólitos biliares, usando a atividade EROD como análise auxiliar. Coletas mensais foram realizadas em três regiões da Baía de Santos entre junho e dezembro de 2005. As espécies escolhidas foram: Stellifer rastrifer, Micropogonia furnieri, Nebris microps e Sphoeroides testudineus. Os metabólitos foram analisados através de cromatógrafo a líquido com detector de fluorescência (HPLC/F). A concentração de metabólitos biliares e de atividade EROD variou, respectivamente de 65,5 a 589 g.g-1 de bile e 6,88 a 262 pmol.min-1.mg-1 de proteína. Os níveis de metabólitos de fenantreno e benzo(a)pireno foram menores na espécie N. microps e maiores na S. testudineus, não havendo diferenças significativas entre as espécies para os metabólitos de naftaleno. Não houve diferenças significativas dos metabólitos estudados entre os locais e períodos de coleta. A biodisponibilidade de PAHs na Baía de Santos foi evidenciada pelos metabólitos e confirmada pela atividade EROD. / Marine environments near urban areas, such as Santos Bay, are subjected to toxic contaminants input, as polycyclic aromatic hydrocarbons (PAHs). The PAHs bioavailability can be evaluated through biomarkers, such as biliary metabolites and 7-ethoxyresorufin-O-deethylase activity (EROD). The goal of the present study was to evaluate the PAH bioavailability in Santos Bay through the biliary metabolites, and the EROD activity as an auxiliary analysis. The samples were collected in three different regions of Santos Bay. The chosen species were: Stellifer rastrifer, Micropogonia furnieri, Nebris microps e Sphoeroides testudineus. The metabolites were analyzed through a high performance liquid chromatograph with fluorescence detector (HPLC/F). The metabolites and the EROD activity concentration varied, respectively, from 65,5 to 589 g.g-1 of bile and 6,88 a 262 pmol.min-1.mg-1 of protein. The phenanthrene and benzo(a)pirene metabolites levels were lower to N. microps and higher to S. testudineus. The naphthalene metabolites did not present significant differences among the species. There were no significant differences in the metabolites for the sampling areas and the period of collection. The PAHs bioavailability was evidenced by the metabolites and confirmed through the EROD activity.

Le cholangiocarcinome (CC) est une tumeur maligne au pronostic péjoratif dont le traitement repose sur la résection chirurgicale. Il représente 3 % de l’ensemble des cancers digestifs et il est la deuxième tumeur primitive du foie, en fréquence, derrière le carcinome hépatocellulaire. L’âge moyen est de 70 ans avec une prédominance masculine. On distingue actuellement les cholangiocarcinomes intra et extra-hépatiques. La survie est inférieure à 5% à 5 ans tous stades confondues. 60 à 70 % sont des tumeurs de la convergence des canaux biliaires appelées également tumeurs de Klatskin.Le but de ce travail était de répondre aux interrogations persistantes concernant le cholangiocarcinome péri-hilaire (CCPH) en appliquant différentes méthodes statistiques sur différentes bases de données et revue de la littérature.Les trois axes principaux de ce travail s’articulent selon la temporalité de prise en charge, du diagnostic aux suites post-opératoires en passant par la mise en condition préopératoire.Le premier axe repose sur une base de données locale (registre de cancer digestif du Calvados). Les résultats montrent que le CCPH constitue seulement un tiers des cholangiocarcinomes dans la population générale, que son taux d’incidence est stable avec néanmoins une diminution d’incidence, bien que non-significative, chez les femmes ayant un CCPH et que le sexe féminin est un facteur pronostic négatif pour la survie à 5 ans. Le deuxième axe concernait la prise en charge préopératoire des patients, notamment l’optimisation préopératoire du foie restant par le drainage biliaire. Ce travail repose sur deux méta-analyses. Il a permis de mettre en évidence la supériorité de la voie radiologique sur la voie endoscopique concernant les complications liées à la procédure mais en revanche, l’absence de différence significative sur la morbi-mortalité post-résection hépatique, la survie à 5 ans, la survie sans récidive et le taux de dissémination liée à la procédure quand les procédures sont étudiées en intention de traiter. Nos résultats suggèrent qu’un mauvais choix de voie d’abord pour réaliser le drainage biliaire conduit à des échecs répétés qui influencent la récidive tumorale et donc la survie. Le troisième axe s’intéressait aux facteurs pronostiques de morbi-mortalité immédiates post-résection hépatique à partir d’une base de données Européenne (base de l’association Française de chirurgie). Les résultats montrent que la surface corporelle ≥ 1.82 m², l’hyperbilirubinémie > 50 µmol/l et la résection hépatique droite sont des facteurs prédictifs indépendants influençant la mortalité post-opératoire à 30 jours. / Cholangiocarcinoma (CC) is a malignant tumor with a poor prognosis. Its treatment is based on surgical resection. It accounts for 3% of all digestive cancers and is the second primary tumor of the liver, in frequency, after hepatocellular carcinoma. The average age is 70 years old with male predominance. At present intra and extrahepatic cholangiocarcinomas are distinguished. Survival rate is less than 5% at 5 years in all stages. 60 to 70% are tumors of the biliary convergence also called Klatskin tumors.The aim of this work was to answer persistent questions about peri-hilar cholangiocarcinoma (PHCC) by applying different statistical methods on different databases and review of the literature.The three main axes of this work are articulated according to the temporality of management, from the diagnosis to the postoperative follow-up, going through the preoperative setting.The first axis is based on a local database (registry of digestive cancer of Calvados). The results show that PHCC accounts for only one third of cholangiocarcinomas in the general population, that its incidence rate is stable with a decrease in incidence, although not significant, in women having PHCC and that female gender is a negative prognostic factor for 5-year survival. The second axis concerned the preoperative management of patients, including preoperative optimization of the remaining liver by biliary drainage. This work is based on two Meta-analyzes. It made it possible to highlight the superiority of the radiological way in the endoscopic way concerning the complications related to the procedure but on the other hand, the absence of significant difference on the morbi-mortality post hepatic resection, the survival at 5 years, the recurrence free survival and the rate of dissemination related to the procedure when the procedures are studied in intent to treat. Our results suggest that a poor choice of pathway for achieving biliary drainage leads to repeated failures that influence tumor recurrence and thus survival. The third axis was concerned with the prognostic factors of immediate morbidity and mortality after hepatic resection from a European database (base of the French association of surgery). The results show that body surface area ≥ 1.82 m², hyperbilirubinemia > 50 μmol / l and right hepatic resection are independent predictors influencing post-operative mortality at 30 days.

The face of transplantation has changed in recent decades. The improvement can be observed not only in terms of survival, but also the improved quality of life after this demanding procedure. This is one of the reasons why quality of life is one of the factors to consider (Durant, 2019). This is also due to the fact that in today's modern society one does not only want to survive, but wants to live fully. He wants to benefit his family and the society in which he lives. He wants to do his hobbies. Everybody wants to be active physically and also mentally. Today, quality of life is considered an indicator suitable for assessing physical, mental and social health (Chrastina, 2015). Methodology: The aim of this work is to evaluate how patients after liver transplantation perceive different domains related to quality of life and whether the results are different depending on the time elapsed from transplantation. For the purposes of the research was chosen a quantitative method using a questionnaire. A standardized WHOQOL BREF was used. The questionnaire contains 24 closed questions, which contain four domains and two questions themselves. Two separate questions assess the overal quality of life and overall health. The questionnaire was supplemented by two questions, which were aimed at obtaining...

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13138号 / 論医博第2138号 / 新制||医||1025(附属図書館) / (主査)教授 伊達 洋至, 教授 坂井 義治, 教授 武藤 学 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background The number of liver resections is constantly rising over the last decades. Despite the reduction of overall mortality and morbidity in liver surgery, biliary leakage is still a relevant postoperative complication that can lead to a fatal postoperative course. Aim of this analysis is the identification of specific risk factors for postoperative biliary complications after liver resections and the development of a predictive biliary leakage risk score. Methods A single-center, retrospective analysis of 844 liver resections performed in the Department of Visceral, Thoracic and Vascular Surgery, Technische Universität Dresden, between 1/2013 and 12/2019 is conducted to identify risk factors for postoperative biliary leakage and a risk score for biliary leakage after hepatectomy is established based on multivariate regression. The score has been validated by an independent validation cohort consisting of 142 patients. Results Overall morbidity is 43.1% with 36% surgical complications and an overall mortality of 4.3%. Biliary leakage occurred in 15.8% of patients. A predictive score for postoperative biliary leakage based on age, major resection, pretreatment with FOLFOX/cetuximab and operating time is created. Patients are stratified to low (< 15%) and high (> 15%) risk with a sensitivity of 67.4% and a specificity of 70.7% in development cohort and a specificity of 68.2% and sensitivity of 75.8% in validation cohort. Conclusions The presented score is robust and has been validated in an independent patient cohort. Depending on the calculated risk, prevention or early treatment can be initiated to avoid bile leakage and to improve postoperative course.

Introdução: A maioria dos pacientes acometidos pela neoplasia que envolve a confluência biliopancreática é diagnosticada em fase avançada. A Colangiopancreatografia Retrógrada Endoscópica (CPRE) é o método de escolha para a drenagem da via biliar obstruída. Todavia, existe um índice de insucesso em torno de 10%. Nesses casos, técnicas alternativas serão aplicadas, como drenagem percutânea trans-hepática e drenagens cirúrgicas. Objetivo: Avaliar o sucesso técnico, clínico, qualidade de vida e sobrevida da drenagem biliar pela cirurgia convencional e técnica endoscópica ecoguiada em pacientes portadores de neoplasia maligna da confluência biliopancreática. Método: No período de abril de 2010 a setembro de 2013, foram estudados 32 pacientes portadores de neoplasia maligna da confluência biliopancreática. Todos os que foram incluídos nesse estudo apresentaram falha na drenagem biliar por CPRE. Três deles foram excluídos por insucesso técnico (falha na confecção da anastomose hepaticojejunal e da formação da fístula coledocoduodenal ecoguiada). O Grupo I foi formado por 15 pacientes submetidos à Hepaticojejunostomia (HJT) em \"Y\" de Roux e derivação gastrojejunal. O Grupo II foi formado por 14 pacientes submetidos à coledocoduodenostomia ecoguiada (CDT). O sucesso clínico foi avaliado pela queda da bilirrubina sérica total em mais de 50% nos sete primeiros dias após o procedimento. A qualidade de vida foi avaliada pelo questionário SF-36 e a sobrevida pela curva de Kaplan-Meier. Resultados: O sucesso técnico foi de 93,75% (15/16) no Grupo I e de 87,5% (14/16) no Grupo II (p = 0,598). O sucesso clínico ocorreu em 14 (93,33%) pacientes pertencentes ao Grupo I e em 10 (71,43%) do Grupo II. Não houve diferença estatisticamente significativa (p = 0,169). O comportamento médio dos escores de qualidade de vida foi estatisticamente igual entre as técnicas ao longo do seguimento (p > 0,05 Técnica * Momento). Houve alteração média estatisticamente significativa ao longo do seguimento nos escores de capacidade funcional, saúde física, dor, aspectos sociais, aspectos emocionais e saúde mental em ambas as técnicas (p < 0,05). O escore de saúde mental foi, em média, estatisticamente maior nos do Grupo II (CDT) em todos os momentos (p = 0,035). O tempo médio de sobrevida daqueles pertencentes ao Grupo I foi de 82,27 dias e os do Grupo II, de 82,36 dias. Sessenta por cento dos pertencentes ao Grupo I faleceram até 90 dias após o procedimento cirúrgico. Por outro lado, 42,9% dos submetidos à CDT faleceram no mesmo período. Não houve diferença estatisticamente significativa no tempo de sobrevida entre os Grupos (p = 0,389). Conclusão: Os dados relacionados aos sucessos técnico, clínico, qualidade de vida e sobrevida foram semelhantes em ambos os grupos, não se verificando diferença estatisticamente significativa / Introduction: Most patients with neoplasm in the biliopancreatic junction are diagnosed at an advanced stage. Endoscopic retrograde cholangiopancreatography (ERCP) is the method of choice for drainage of obstructed biliary tract. However, there is a failure rate of about 10%. In such cases, alternative techniques, such as, percutaneous transhepatic drainage and surgical drainage are applied. Aim: To evaluate the technical and clinical success, quality of life and patient survival of biliary drainage by conventional surgery and endosonography-guided technique in patients with malignant neoplasm of the biliopancreatic junction. Methodology: From April 2010 to September 2013, 32 patients with malignant neoplasm of the biliopancreatic junction were studied. All patients included in this study had failed biliary drainage by ERCP. Three patients were excluded due to technical failure (failure in the construction of hepatico-jejuno anastomosis and formation of endosonography-guided choledochoduodenal fistula). Group I comprised of 15 patients who underwent Roux-en-Y hepaticojejunostomy (HJT) and gastrojejunal bypass. Group II consisted of 14 patients who underwent endosonography-guided choledochoduodenostomy (CDT). Clinical success was assessed by the decrease of more than 50% in total serum bilirubin in the first seven days after the procedure. Quality of life was assessed by SF-36 questionnaire and survival by Kaplan-Meier curve. Results: Technical success rate was 93.75% (15/16) in group I and 87.5% (14/16) in group II (p = 0.598). Clinical success occurred in 14 (93.33%) patients in group I and 10 (71.43%) patients in group II. There was no significant statistically difference (p = 0.169). The average quality of life score were statistically equal between the techniques during follow-up (p > 0.05 * Technical Moment). There were statistically significant mean changes during follow-up of functional capacity score, physical health, pain, social functioning, emotional and mental health aspects in both techniques (p < 0.05). The mental health score was, on average, statistically higher in group II (CDT) at all times (p = 0.035). The median survival time of patients in group I was 82.27 days and Group II patients was 82.36 days. Sixty percent of patients in group I died within 90 days after the surgical procedure. On the other hand, 42.9% of the patients who underwent CDT died in the same period. There was no statistically significant difference in survival time between the groups (p = 0.389). Conclusion: Data relating to technical and clinical success, quality of life and survival were similar in both groups and there were no statistically significant differences

Atresia de vias biliares (AVB) é uma hepatopatia colestática específica da criança, de etiologia desconhecida, com evolução para fibrose hepática precoce. AVB é a principal causa de cirrose na infância e principal indicação de transplante hepático pediátrico (Tx). Compreender os fatores envolvidos na progressão da fibrose é fundamental para estabelecer tratamentos efetivos nas hepatopatias crônicas. Identificar padrões histopatológicos associados ao prognóstico da AVB permitiria melhor planejamento dos centros de transplante e adequado aconselhamento familiar. OBJETIVO: Estabelecer padrões de marcadores histopatológicos e de imunofluorescência para colágenos em biópsias hepáticas iniciais e finais de pacientes com AVB submetidos a tratamento cirúrgico. Correlacionar esses marcadores com o prognóstico da doença, definido com base no tempo de evolução até realização do Tx. MÉTODO: Avaliação histológica de alterações biliares e fibrose hepática e histomorfometria da fibrose marcada por picrossírius e da deposição dos colágenos tipos I, III, IV e V marcados por imunofluorescência indireta (IF), em biópsias hepáticas iniciais e finais de 36 pacientes com AVB submetidos à hepatoportoenterostomia de Kasai (KPE) e ao Tx nos últimos 20 anos em nossa instituição. RESULTADOS: A mediana das idades de realização da KPE foi de 12,5 semanas (6-20) e do Tx foi de 27 meses (6-120). Reação ductular e malformação de placa ductal foram mais intensas nas biópsias iniciais (p < 0,05), enquanto fibrose hepática e ductopenia apresentaram padrão progressivo (p < 0,001), sem correlações com a idade de realização da KPE nem com o tempo de evolução até Tx. A morfometria da fibrose hepática marcada pelo picrossírius nas biópsias iniciais apresentou correlação positiva com a idade da KPE (p = 0,01), mas não com a idade do Tx (p = 0,24). A deposição perissinusoidal dos colágenos dos tipos III e V foi mais intensa nas biópsias iniciais (p < 0,01), enquanto os colágenos dos tipos I e IV apresentaram padrão de deposição progressiva (p < 0,01). Pacientes com maior deposição perissinusoidal de colágeno tipo I nas biópsias iniciais apresentaram curva de tempo de evolução até Tx sugerindo pior prognóstico (p = 0,04). CONCLUSÃO: Marcadores histopatológicos de alterações biliares, fibrose hepática e deposição de colágenos apresentaram características evolutivas distintas nas fases inicial e final da AVB, sem correlação com o tempo de evolução até Tx. A morfometria da deposição perissinusoidal de colágeno tipo I em biopsias iniciais marcadas por IF pode ser correlacionada ao tempo de evolução até Tx em pacientes com AVB operada / Biliary atresia (BA) is a specific cholestatic liver disease of unknown etiology that affects children and progresses to early hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Understanding the factors involved in the progress of fibrosis is essential to establish effective treatment to chronic liver disease. Histopathological markers in liver biopsies could be useful to predict progression to end stage disease and to make it possible to improve planning in transplantation centers and parental orientation. OBJECTIVE: To establish histopathological or immunohistochemical markers in initial or final liver biopsies of BA patients and correlate those markers with prognosis, as defined by progression time lapse until LTx. METHOD: Histological analysis of multiple parameters of biliary alterations and morphometrical assessment of liver fibrosis were performed, besides indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA submitted to Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years in a single center. RESULTS: The median of the ages at KPE was 12.5 weeks (6-20) and at LTx was 27 months (6-120). Ductular reaction and ductal plate malformation were more severe in the initial biopsies (p < 0.05), while ductopenia and liver fibrosis were more severe in final biopsies (p < 0.001), though without correlation with age at KPE nor with progression time lapse until LTx. Morphometrical assessment of liver fibrosis marked by picrosirius red in initial biopsies demonstrated positive correlation with age at KPE (p = 0.01) but not with age at LTx (p = 0.24). The perisinusoidal deposition of type III and V collagens was more extended in the initial biopsies (p < 0.01), while type I and IV collagens deposition indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curve until LTx (p = 0.04). CONCLUSION: Biliary alterations, liver fibrosis and collagens deposition demonstrated distinctive progression findings in the initial or final phases of the BA, without prognostic correlation. Morphometrical assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsies can be correlated with progression time until LTx in patients with post-surgical BA

Atresia de vias biliares (AVB) é uma hepatopatia colestática específica da criança, de etiologia desconhecida, com evolução para fibrose hepática precoce. AVB é a principal causa de cirrose na infância e principal indicação de transplante hepático pediátrico (Tx). Compreender os fatores envolvidos na progressão da fibrose é fundamental para estabelecer tratamentos efetivos nas hepatopatias crônicas. Identificar padrões histopatológicos associados ao prognóstico da AVB permitiria melhor planejamento dos centros de transplante e adequado aconselhamento familiar. OBJETIVO: Estabelecer padrões de marcadores histopatológicos e de imunofluorescência para colágenos em biópsias hepáticas iniciais e finais de pacientes com AVB submetidos a tratamento cirúrgico. Correlacionar esses marcadores com o prognóstico da doença, definido com base no tempo de evolução até realização do Tx. MÉTODO: Avaliação histológica de alterações biliares e fibrose hepática e histomorfometria da fibrose marcada por picrossírius e da deposição dos colágenos tipos I, III, IV e V marcados por imunofluorescência indireta (IF), em biópsias hepáticas iniciais e finais de 36 pacientes com AVB submetidos à hepatoportoenterostomia de Kasai (KPE) e ao Tx nos últimos 20 anos em nossa instituição. RESULTADOS: A mediana das idades de realização da KPE foi de 12,5 semanas (6-20) e do Tx foi de 27 meses (6-120). Reação ductular e malformação de placa ductal foram mais intensas nas biópsias iniciais (p < 0,05), enquanto fibrose hepática e ductopenia apresentaram padrão progressivo (p < 0,001), sem correlações com a idade de realização da KPE nem com o tempo de evolução até Tx. A morfometria da fibrose hepática marcada pelo picrossírius nas biópsias iniciais apresentou correlação positiva com a idade da KPE (p = 0,01), mas não com a idade do Tx (p = 0,24). A deposição perissinusoidal dos colágenos dos tipos III e V foi mais intensa nas biópsias iniciais (p < 0,01), enquanto os colágenos dos tipos I e IV apresentaram padrão de deposição progressiva (p < 0,01). Pacientes com maior deposição perissinusoidal de colágeno tipo I nas biópsias iniciais apresentaram curva de tempo de evolução até Tx sugerindo pior prognóstico (p = 0,04). CONCLUSÃO: Marcadores histopatológicos de alterações biliares, fibrose hepática e deposição de colágenos apresentaram características evolutivas distintas nas fases inicial e final da AVB, sem correlação com o tempo de evolução até Tx. A morfometria da deposição perissinusoidal de colágeno tipo I em biopsias iniciais marcadas por IF pode ser correlacionada ao tempo de evolução até Tx em pacientes com AVB operada / Biliary atresia (BA) is a specific cholestatic liver disease of unknown etiology that affects children and progresses to early hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Understanding the factors involved in the progress of fibrosis is essential to establish effective treatment to chronic liver disease. Histopathological markers in liver biopsies could be useful to predict progression to end stage disease and to make it possible to improve planning in transplantation centers and parental orientation. OBJECTIVE: To establish histopathological or immunohistochemical markers in initial or final liver biopsies of BA patients and correlate those markers with prognosis, as defined by progression time lapse until LTx. METHOD: Histological analysis of multiple parameters of biliary alterations and morphometrical assessment of liver fibrosis were performed, besides indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA submitted to Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years in a single center. RESULTS: The median of the ages at KPE was 12.5 weeks (6-20) and at LTx was 27 months (6-120). Ductular reaction and ductal plate malformation were more severe in the initial biopsies (p < 0.05), while ductopenia and liver fibrosis were more severe in final biopsies (p < 0.001), though without correlation with age at KPE nor with progression time lapse until LTx. Morphometrical assessment of liver fibrosis marked by picrosirius red in initial biopsies demonstrated positive correlation with age at KPE (p = 0.01) but not with age at LTx (p = 0.24). The perisinusoidal deposition of type III and V collagens was more extended in the initial biopsies (p < 0.01), while type I and IV collagens deposition indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curve until LTx (p = 0.04). CONCLUSION: Biliary alterations, liver fibrosis and collagens deposition demonstrated distinctive progression findings in the initial or final phases of the BA, without prognostic correlation. Morphometrical assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsies can be correlated with progression time until LTx in patients with post-surgical BA