CLINICAL, LABORATORIAL AND EVOLUTIONARY ASPECTS OF PEDIATRIC PATIENTS WITH LIVER DISEASE DUE TO ALPHA 1-ANTITRYPSIN DEFICIENCY.

BACKGROUND: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. OBJECTIVE: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. METHODS: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia-bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. RESULTS: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. CONCLUSION: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

Aspectos clínicos, laboratoriais e evolutivos de pacientes pediátricos com doença hepática por deficiência de alfa 1-antitripsina / Clinical, laboratorial and evolutionary aspects of pediatric patients with liver disease due to alpha 1-antitrypsin deficiency

ABSTRACT Background: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. Objective: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. Methods: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia­bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. Results: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. Conclusion: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

RESUMO Contexto: Deficiência de alfa 1-antitripsina (DAAT) é uma doença hereditária, de caráter autossômico codominante. A apresentação da doença hepática varia desde casos assintomáticos até doença terminal, o que dificulta reconhecimento e diagnóstico precoces. É a principal causa de transplante hepático pediátrico após atresia de vias biliares. Objetivo: Descrever as características clínicas, de exames laboratoriais, histológicos, avaliação fenotípica e/ou genética e sobrevida de uma coorte de pacientes pediátricos com DAAT. Métodos: Estudo observacional retrospectivo de 39 pacientes com diagnóstico de DAAT confirmada ou provável (sem fenotipagem ou genotipagem, mas com clínica sugestiva, baixo nível sérico de alfa 1-antitripsina (A1AT) e biópsia hepática com grânulos PAS, diástase resistentes). Variáveis clínicas, laboratoriais, histológicas, presença de hipertensão portal (HP) e sobrevida com fígado nativo foram analisadas. Resultados: Dos 39 pacientes, 66,7% eram do sexo masculino (26/39). A manifestação inicial foi icterícia colestática em 79,5% (31/39). Em 28,2% (11/39) houve necessidade de transplante hepático. O diagnóstico ocorreu com uma idade média de 3,1 anos e, o transplante hepático, 4,1 anos. Dos pacientes com DAAT confirmada, 89,2% (25/28) eram PI*ZZ ou ZZ. O valor médio de A1AT na admissão de pacientes PI*ZZ ou ZZ foi 41,6 mg/dL. Todos os transplantados com fenotipagem ou genotipagem eram PI*ZZ (ou ZZ). Os ictéricos à admissão foram referenciados mais cedo ao serviço especializado e apresentaram níveis mais elevados de GGT e plaquetas à admissão. Não houve diferença significativa na curva de sobrevida ao compararmos icterícia colestática ou não à admissão. Ao comparar os pacientes que progrediram ou não para HP, observou-se níveis mais elevados de AST e APRI escore ao diagnóstico (P=0,011 e P=0,026, respectivamente) e, nas curvas de sobrevida, pacientes com HP apresentaram comprometimento, com 20,2% de sobrevida com fígado nativo em 15 anos. Conclusão: Icterícia é um sinal clínico importante que motiva o encaminhamento ao especialista, mas parece não comprometer a sobrevida com fígado nativo. Pacientes com evolução para HP tiveram AST e escore APRi mais elevados à admissão e comprometimento significativo da sobrevida com fígado nativo. Importante atentar a esses sinais no seguimento de pacientes com DAAT.

PREDICTIVE FACTORS OF MORBIDITY ASSOCIATED WITH ESOPHAGEAL VARICEAL BLEEDING IN CHILDREN WITH PORTAL HYPERTENSION.

•Most data on the natural history of portal hypertension come from studies in adults. •The morbidity rate of upper gastrointestinal bleeding in children with portal hypertension tend to be underestimated. •This study showed the relevance of morbidity rates after variceal hemorrhage in pediatric patients, especially those with cirrhosis. •Patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications secondary to upper gastrointestinal bleeding and should be closely monitored. Background - Most data on the natural history of portal hypertension come from studies in adults. The morbidity rate of upper gastrointestinal bleeding (UGIB) in children with portal hypertension has not been systematically characterized. Objective - To describe the morbidity and mortality of UGIB in pediatric patients with portal hypertension and identify predictive factors for the occurrence of its main complications. Methods - This retrospective study included pediatric patients with cirrhotic portal hypertension or with extrahepatic portal vein obstruction (EHPVO). Mortality and UGIB complications within a period of up to 6 weeks of the bleeding were investigated. To determine the predictive factors of morbidity, a multivariate analysis was performed using logistic regression; all results were considered significant at P<0.05. Results - A total of 86 patients (51.2% with EHPVO and 48.8% with cirrhosis) had 174 bleeding events. Ascites was the most common complication (43.1% of all cases), being more prevalent in patients with cirrhosis (P<0.001). Cirrhosis was a predictor of the occurrence of any morbidity (OR 20.3). The need for blood transfusion was predictor of at least one complication (OR 5.8), ascites (OR 7.2) and infections (OR 3.8) in the general group and at least one complication (OR 11.3) and ascites (OR 5.8) in cirrhotic patients. The need for expansion was a predictor of any morbidity (OR 4.6) and infections (OR 3.9) in the general group, in addition to being predictor of infection in cirrhotic patients (OR 5.4). There were no deaths from UGIB in the six weeks post-bleeding. Conclusion - The study showed the relevance of morbidity after UGIB in pediatric patients with portal hypertension, especially in those with cirrhosis. The patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications related to upper gastrointestinal bleeding and should be closely monitored.

Fatores preditivos de morbidade associada à sangramento de varizes esofágicas em crianças com hipertensão porta / Predictive factors of morbidity associated with esophageal variceal bleeding in children with portal hypertension

ABSTRACT Background: Most data on the natural history of portal hypertension come from studies in adults. The morbidity rate of upper gastrointestinal bleeding (UGIB) in children with portal hypertension has not been systematically characterized. Objective: To describe the morbidity and mortality of UGIB in pediatric patients with portal hypertension and identify predictive factors for the occurrence of its main complications. Methods: This retrospective study included pediatric patients with cirrhotic portal hypertension or with extrahepatic portal vein obstruction (EHPVO). Mortality and UGIB complications within a period of up to 6 weeks of the bleeding were investigated. To determine the predictive factors of morbidity, a multivariate analysis was performed using logistic regression; all results were considered significant at P<0.05. Results: A total of 86 patients (51.2% with EHPVO and 48.8% with cirrhosis) had 174 bleeding events. Ascites was the most common complication (43.1% of all cases), being more prevalent in patients with cirrhosis (P<0.001). Cirrhosis was a predictor of the occurrence of any morbidity (OR 20.3). The need for blood transfusion was predictor of at least one complication (OR 5.8), ascites (OR 7.2) and infections (OR 3.8) in the general group and at least one complication (OR 11.3) and ascites (OR 5.8) in cirrhotic patients. The need for expansion was a predictor of any morbidity (OR 4.6) and infections (OR 3.9) in the general group, in addition to being predictor of infection in cirrhotic patients (OR 5.4). There were no deaths from UGIB in the six weeks post-bleeding. Conclusion: The study showed the relevance of morbidity after UGIB in pediatric patients with portal hypertension, especially in those with cirrhosis. The patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications related to upper gastrointestinal bleeding and should be closely monitored.

RESUMO Contexto: A maioria dos dados sobre a história natural da hipertensão porta provém de estudos em adultos. A morbidade associada à hemorragia digestiva alta (HDA) em crianças com hipertensão porta ainda não foi sistematicamente estudada. Objetivo: Descrever a morbimortalidade da HDA em pacientes pediátricos com hipertensão porta e identificar fatores preditivos para a ocorrência de suas principais complicações. Métodos: Este estudo retrospectivo incluiu pacientes pediátricos com hipertensão porta cirrótica ou com obstrução extra-hepática da veia porta (OEHVP). A mortalidade e as complicações da HDA foram estudadas até seis semanas após o sangramento. Para determinar os fatores preditivos de morbidade, foi realizada análise multivariada por meio de regressão logística; todos os resultados foram considerados significativos com P<0,05. Resultados: Oitenta e seis pacientes (51,2% com OEHVP e 48,8% com cirrose) tiveram 174 eventos hemorrágicos. A ascite foi a complicação mais comum (43,1% de todos os casos), sendo mais prevalente em pacientes com cirrose (P<0,001). A cirrose foi preditor da ocorrência de pelo menos uma complicação (OR 20,3). A necessidade de transfusão sanguínea foi preditora de pelo menos uma complicação (OR 5,8), ascite (OR 7,2) e infecções (OR 3,8) no grupo geral e pelo menos uma complicação (OR 11,3) e ascite (OR 5,8) nos cirróticos. A necessidade de expansão foi preditor de qualquer morbidade (OR 4,6) e infecções (OR 3,9) no grupo geral, além de ser preditor de infecção em cirróticos (OR 5,4). Não houve óbitos por HDA nas 6 semanas pós-sangramento. Conclusão: O estudo mostrou a relevância da morbidade após HDA em pacientes pediátricos com hipertensão porta, principalmente naqueles com cirrose. Os pacientes com instabilidade hemodinâmica que necessitam de transfusão de sangue ou expansão na admissão têm risco aumentado de complicações relacionadas à hemorragia digestiva alta e devem ser monitorados de perto.

Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant.

The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis.

Non-invasive Predictors of Esophageal Varices With a High Risk of Bleeding in Pediatric Cirrhotic Patients.

OBJECTIVES: To evaluate non-invasive predictive factors of varices with a high risk of bleeding in pediatric cirrhotic patients. METHODS: This retrospective, cross-sectional study included data from 158 children with cirrhosis, median age of 5.38 years (interquartile [IQ] 2.08-11.52 years), and no history of upper gastrointestinal bleeding. Patients underwent an endoscopy to screen for esophageal varices. Varices with a high risk of bleeding were defined as those with a medium to large caliber, presence of red spots, or the presence of gastric varices and identified as high-risk varices (HRV). Laboratory and clinical factors were evaluated as possible predictors of HRV. RESULTS: HRV were detected in 30 children (19%) after the first endoscopy. In the multivariate analysis, only the risk score (RS), as described by Park et al, and the aspartate aminotransferase-to-platelet ratio index (APRi) were predictive of HRV. The best non-invasive predictor of HRV was the RS with an area under the receiver operating characteristic curve of 0.764. When used a cut-off point of -1.2, the sensitivity of the RS was 90% and specificity was 53%. The use of RS or APRi correctly identified 96% of children with HRV. CONCLUSIONS: The described predictors allow the correct identification of patients with HRV. The association of RS >-1.2 or APRi >1.4 has a good sensitivity to identify HRV and to prevent unnecessary endoscopy in about one-third of children with no HRV.

Endoscopic prophylaxis and factors associated with bleeding in children with extrahepatic portal vein obstruction.

OBJECTIVES: This study aimed to evaluate factors associated with upper digestive hemorrhage and primary and secondary endoscopic prophylaxis outcomes in children with extrahepatic portal vein obstruction. METHODS: This observational and prospective study included 72 children with extrahepatic portal vein obstruction who were followed from 2005 to 2017. Risk factors associated with upper digestive hemorrhage and the results of primary and secondary prophylaxis of these patients were evaluated. RESULTS: Fifty patients (69.4%) had one or more episodes of bleeding during follow-up, with a median age at first hemorrhage of 4.81 years. The multivariate analysis showed that medium- to large-caliber esophageal varices were associated with an 18-fold risk of upper digestive hemorrhage (95% CI: 4.33-74.76; p < 0.0001). Primary prophylaxis was administered to 14 patients, with eradication in 85.7%; however, 14.3% of these patients had hemorrhages during the follow-up period and 41.7% had a relapse of varices. Secondary prophylaxis was administered to 41 patients. Esophageal varices were eradicated in 90.2% of patients. There were relapse and re-bleeding of esophageal varices in 45.9% and 34.1% of the children, respectively. CONCLUSION: Primary and secondary endoscopic prophylaxes showed high rates of esophageal varix eradication, but with significant relapses. Eradication of esophageal varices cannot definitively prevent recurrent upper digestive hemorrhage, since bleeding from alternate sites can occur. Medium- and large-caliber esophageal varices were associated with upper digestive hemorrhage in patients with extrahepatic portal vein obstruction. To the best of the authors' knowledge, this study is the first to evaluate bleeding risk factors in children with extrahepatic portal vein obstruction.

Colelitíase na infância e adolescência: abordagem diagnóstica e tratamento / Cholelithiasis in childhood and adolescence: diagnostic approach and treatment

Com exceção dos casos decorrentes de doença hemolítica crônica, a colelitíase biliar é pouco comum na infância e adolescência quando comparada aos adultos. No entanto, nas últimas décadas observou-se importante aumento da incidência da doença na pediatria, principalmente em adolescentes do sexo feminino. Os fatores de risco associados à colelitíase têm se assemelhado àqueles encontrados nos adultos e o cálculo de colesterol é o principal responsável pelo aumento da prevalência. Acredita-se que a maioria dos pacientes pediátricos com colelitíase biliar apresente sintomas inespecíficos; a cólica biliar típica é encontrada mais frequentemente em crianças mais velhas. O tratamento padrão para a colelitíase sintomática é o tratamento cirúrgico com retirada da vesícula biliar, sendo a colecistectomia videolaparoscópica preferível à cirurgia aberta devido ao menor tempo de recuperação e de internação hospitalar. Contudo, na colelitíase assintomática o tratamento deve ser individualizado, sendo indicada a cirurgia em casos selecionados. O objetivo desta revisão é apresentar os principais aspectos da doença calculosa biliar na infância e contribuir para maior suspeição clínica da doença entre os pediatras, aprimorando a abordagem diagnóstica e a definição terapêutica adequada.

Excluding the cases resulting from chronic hemolytic disease, cholelithiasis is uncommon in childhood and adolescence when compared to adults. However, in recent decades there has been noted an increased incidence of the disease in pediatrics, especially in female adolescents. The risk factors associated with cholelithiasis have been similar to those found in adults and cholesterol stones are the main responsible for the increase of the prevalence. The majority of pediatric patients with cholelithiasis have no specific symptoms; typical biliary colic is found more often among older children. The standard treatment for symptomatic cholelithiasis is surgery to remove the gallbladder; the laparoscopic cholecystectomy is preferable to open surgery because of the shorter recovery time and hospital stay. However, in asymptomatic cholelithiasis treatment must be individualized and surgery is indicated in selected cases. The aim of this review is to present the main aspects of gallstone disease in childhood and contribute to greater clinical suspicion of the disease among pediatricians, improving the diagnostic approach and the appropriate therapeutic definition.

Doença Hepática Gordurosa Não Alcoólica em crianças e adolescentes / Non-alcoholic fatty liver disease in childhood and adolescence

A obesidade infantil é uma epidemia mundial. São várias as comorbidades associadas à obesidade, destacando-se a doença hepática gordurosa não alcoólica (DHGNA), um termo abrangente que envolve desde a esteatose hepatocelular simples até quadros mais avançados de esteato-hepatite, fibrose e cirrose hepática. Atualmente, é a segunda maior causa de transplante hepático em adultos nos Estados Unidos, com potencial de se tornar a primeira nas próximas décadas. Associado a este panorama, ainda existe o desafio do diagnóstico, uma vez que os critérios clínicos e laboratoriais ainda são controversos, especialmente em crianças. A biópsia é o padrão ouro, entretanto é um procedimento invasivo e sujeito a riscos. Por isso, a dosagem de enzimas hepáticas e a ultrassonografia abdominal são utilizadas para triagem e avaliação, apesar de suas limitações. O tratamento de DHGNA deve obrigatoriamente incluir a abordagem da obesidade. Por isso, os pilares do tratamento envolvem a mudança do estilo de vida e dos hábitos alimentares. Embora a eficácia de várias medicações venha sendo estudada, a alimentação saudável e a atividade física permanecem como a mais importante estratégia de prevenção e tratamento da DHGNA na infância e adolescência. A equipe multidisciplinar deve, junto ao paciente e a família, construir uma rotina de hábitos alimentares e atividades físicas adequadas para cada caso. (AU)

Childhood obesity is a worldwide epidemic. There are several comorbidities associated with obesity, including non-alcoholic fatty liver disease (NAFLD), a wide term that ranges from a hepatocellular steatosis to more advanced steatohepatitis, fibrosis and liver cirrhosis. This is the second major cause of liver transplant in adults in the United States, with the potential to become the first one in the next few decades. Associated with this scenario, the challenge of diagnosis still exists, since screening is still controversial, especially in children. Biopsy is the gold standard, but it is an invasive and risky procedure. Therefore liver enzymes and abdominal ultrasound are used for screening and assessment although their limitations. Treatment of NAFLD should involve an approach to obesity with focus in lifestyle intervention and healthy diet. While the efficacy of several medications has been investigated in children, healthy diet and physical activity remain the only prevention and treatment strategies for paediatric NAFLD. A multidisciplinary team should, together with the patient and a family, build a routine of healthy eating and physical activities (AU)

HLA-DRB1 GENE POLYMORPHISMS IN PEDIATRIC PATIENTS WITH TYPE 1 AUTOIMMUNE HEPATITIS AND TYPE 1 AUTOIMMUNE HEPATITIS OVERLAP SYNDROME WITH AUTOIMMUNE CHOLANGITIS.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

Polimorfismos do gene HLA-DRB1 em pacientes pediátricos com hepatite autoimune tipo 1 e hepatite autoimune associada à colangite autoimune / Hla-drb1 gene polymorphisms in pediatric patients with type 1 autoimmune hepatitis and type 1 autoimmune hepatitis overlap syndrome with autoimmune cholangitis

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

RESUMO CONTEXTO: Hepatite autoimune (HAI) é uma doença hepática inflamatória crônica, rara, associada à perda da tolerância imunológica aos auto-antígenos. A susceptibilidade à HAI é parcialmente determinada pela presença de genes relacionados ao antígeno leucocitário humano (HLA), principalmente variantes alélicas do DRB1. OBJETIVO: O objetivo deste estudo foi investigar a frequência de polimorfismos no gene HLA-DRB1 em crianças e adolescentes com HAI tipo 1 e HAI tipo 1 associada à colangite autoimune, em comparação com indivíduos saudáveis pareados por sexo e idade (grupo controle). MÉTODOS: Este é um estudo transversal de 25 pacientes pediátricos com diagnóstico de HAI tipo 1 e 18 com HAI associada à colangite autoimune. Cinquenta e sete indivíduos saudáveis foram incluídos como controles. Os polimorfismos do gene HLA-DRB1 foram avaliados por PCR e incluíram HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07 e HLA-DRB1*13. RESULTADOS: Nossos resultados mostraram que a presença do alelo HLA-DRB1*13 aumentou a chance de colangite autoimune (OR=3,96; IC 1,07 a 14,61; P=0,04). O HLA-DRB1*04 e o HLA-DRB1*07 não apresentam associação com a HAI e colangite autoimune no grupo de pacientes mais jovens. CONCLUSÃO: Este trabalho demonstra uma associação dos principais polimorfismos no gene HLA-DRB1 à HAI com ou sem colangite na população brasileira.

MULTIVARIATE ANALYSIS OF BILIARY FLOW-RELATED FACTORS AND POST-KASAI SURVIVAL IN BILIARY ATRESIA PATIENTS.

BACKGROUND: Biliary atresia represents the most common surgically treatable cause of cholestasis in newborns. If not corrected, secondary biliary cirrhosis invariably results. OBJECTIVE: To evaluate, through multivariate analysis, the prognostic factors associated with the presence of biliary flow and survival with the native liver following Kasai portoenterostomy. METHODS: The study analyzed data from 117 biliary atresia patients who underwent portoenterostomy and had suitable histological material for evaluation. A logistic regression model was used to assess the presence of biliary flow. Survival was investigated through Kaplan-Meier curves and Cox-adjusted models. RESULTS: One third of patients achieved biliary flow and the median age at surgery was 81 days. Age at surgery, albumin, postoperative complications, biliary atresia structural malformation (BASM), liver architecture, larger duct diameter at porta hepatis, and cirrhosis (Ishak score) were the initial variables for the multivariate analysis. Age at surgery >90 days was the only variable associated with the absence of biliary drainage. Survival analysis revealed that the absence of biliary flow (P<0.0001), age at surgery >90 days (P=0.035), and the presence of BASM (P<0.0001), alone, could predict death or need for liver transplantation. Multivariate analysis demonstrated that the absence of biliary flow (P<0.0001 hazard ratio [HR] 6.25, 95% confidence interval [CI] 3.19-12.22) and the presence of BASM (P=0.014 HR 2.16, 95% CI 1.17-3.99) were associated with lowest survival with the native liver. CONCLUSION: Age at surgery >90 days was associated with absence of biliary flow. The presence of biliary drainage and the absence of structural malformations are cornerstone features for higher survival rates with the native liver.

Análise multivariada de variáveis relacionadas ao fluxo biliar e sobrevida pós-Kasai em pacientes com atresia biliar / Multivariate analysis of biliary flow-related factors and post-kasai survival in biliary atresia patients

ABSTRACT BACKGROUND: Biliary atresia represents the most common surgically treatable cause of cholestasis in newborns. If not corrected, secondary biliary cirrhosis invariably results. OBJECTIVE: To evaluate, through multivariate analysis, the prognostic factors associated with the presence of biliary flow and survival with the native liver following Kasai portoenterostomy. METHODS: The study analyzed data from 117 biliary atresia patients who underwent portoenterostomy and had suitable histological material for evaluation. A logistic regression model was used to assess the presence of biliary flow. Survival was investigated through Kaplan-Meier curves and Cox-adjusted models. RESULTS: One third of patients achieved biliary flow and the median age at surgery was 81 days. Age at surgery, albumin, postoperative complications, biliary atresia structural malformation (BASM), liver architecture, larger duct diameter at porta hepatis, and cirrhosis (Ishak score) were the initial variables for the multivariate analysis. Age at surgery >90 days was the only variable associated with the absence of biliary drainage. Survival analysis revealed that the absence of biliary flow (P<0.0001), age at surgery >90 days (P=0.035), and the presence of BASM (P<0.0001), alone, could predict death or need for liver transplantation. Multivariate analysis demonstrated that the absence of biliary flow (P<0.0001 hazard ratio [HR] 6.25, 95% confidence interval [CI] 3.19-12.22) and the presence of BASM (P=0.014 HR 2.16, 95% CI 1.17-3.99) were associated with lowest survival with the native liver. CONCLUSION: Age at surgery >90 days was associated with absence of biliary flow. The presence of biliary drainage and the absence of structural malformations are cornerstone features for higher survival rates with the native liver.

RESUMO CONTEXTO: A atresia biliar representa a principal causa de colestase tratada cirurgicamente durante o período neonatal. Se a criança não for operada, ela evolui invariavelmente para cirrose biliar secundária. OBJETIVO: Avaliar, através de análise multivariada, os fatores prognósticos associados à presença de fluxo biliar e à sobrevida com fígado nativo após a realização da portoenterostomia de Kasai. MÉTODOS: O estudo analisou 117 pacientes com atresia biliar submetidos à portoenterostomia e com material histológico adequado para avaliação. O modelo de regressão logística foi utilizado para avaliar a presença de fluxo biliar. Sobrevida foi estudada através das curvas Kaplan-Meier e ajuste do modelo de Cox. RESULTADOS: Um terço dos pacientes obteve fluxo biliar e a mediana de idade à cirurgia foi de 81 dias. Idade à cirurgia, albumina, complicação pós-operatória, BASM (do inglês, biliary atresia structural malformation), arquitetura hepática, diâmetro do maior canalículo no porta hepatis e cirrose, segundo o escore de Ishak, foram as variáveis iniciais da análise multivariada. Idade à cirurgia maior que 90 dias de vida foi a única variável associada à ausência de drenagem biliar. A análise de sobrevida mostrou que as variáveis: ausência de fluxo biliar (P<0,0001), idade à cirurgia maior que 90 dias (P=0,035) e presença de BASM (P<0,0001), isoladamente, predizem morte ou necessidade de transplante hepático. Na análise multivariada, ausência de fluxo biliar (P<0,0001 HR:6,25 [IC95% 3,19; 12,22]) e presença de BASM (P=0,014 HR:2,16 [IC95% 1,17; 3,99]) mostraram-se associadas, com significância estatística, a menor sobrevida com fígado nativo. CONCLUSÃO: Idade à cirurgia maior que 90 dias foi identificada como fator de risco independente para ausência de fluxo biliar. Além disso, a presença de drenagem biliar e a ausência de malformações estruturais da atresia biliar são variáveis fundamentais para a maior sobrevida com fígado nativo.

Colangite esclerosante primária em crianças e adolescentes / Primary sclerosing cholangitis in children and adolescents

ABSTRACT BACKGROUND: Primary sclerosing cholangitis is a rare disease, but its prevalence has been underestimated in children and adolescents due to broad variation in clinical presentation as well as diagnostic challenges in this life period. OBJECTIVE: To evaluate children and adolescents with primary sclerosing cholangitis and to describe their clinical, laboratorial, histopathological, and cholangiography conditions. METHODS: This is an observational descriptive research that took place from 2005 to 2016 and included all the patients seen in the Outpatient Unit for Pediatric Hepatology of Hospital das Clinicas of UFMG who had been diagnosed with primary sclerosing cholangitis before the age of 18. Diagnosis was established through clinical, laboratory, radiographic and/or histopathologic criteria. Other chronic liver diseases were excluded, as well as secondary causes of cholangitis. Data analysis used statistic resources in SPSS software. Variables were expressed as averages, standard deviation, absolute frequency, and percentage. RESULTS: Twenty-one patients fulfilled criteria to be included in the research sample. Male patients predominated (3.2:1) and average age at diagnosis was 6.7±3.9 years. Five (23.8%) patients had associated inflammatory bowel disease, four had ulcerative colitis and one indeterminate colitis. Signs and symptoms vary and are usually discrete at presentation. The most frequent symptom was abdominal pain (47.6%) followed less frequently by jaundice (28.6%) and itching (14.3%). The reason for medical investigation was asymptomatic or oligosymptomatic enzyme alterations in 33.3% of patients. All patients presented increased hepatic enzymes: aminotransferases, gamma glutamyl transferase, and alkaline phosphatase. Twenty patients had alterations compatible to primary sclerosing cholangitis in their cholangiography exam; one patient had no alterations at magnetic resonance cholangiography, but presented histopathologic alterations that were compatible to small duct cholangitis. Hepatic fibrosis was present in 60% of 15 patients who were biopsied upon admission; cirrhosis being present in four (26.7%) patients. A total of 28.5% of patients had unfavorable outcomes, including two (9.5%) deaths and four (19%) transplants. CONCLUSION: Primary sclerosing cholangitis is a rare disease in childhood and adolescence and its initial diagnosis may be delayed or overlooked due to asymptomatic or unspecific clinical manifestations. The association with inflammatory bowel disease is common. Prognosis may be unfavorable as the disease progresses and hepatic transplant is the definitive treatment.

RESUMO CONTEXTO: A colangite esclerosante primária é uma doença rara, mas sua prevalência tem sido subestimada em crianças e adolescentes, tanto pela variedade de apresentação clínica quanto pela dificuldade diagnóstica neste período. OBJETIVO: Avaliar crianças e adolescentes com colangite esclerosante primária descrevendo seu quadro clínico, laboratorial, histopatológico e colangiográfico. MÉTODOS: Trata-se de um estudo descritivo observacional, de 2005 a 2016, de todos os pacientes atendidos no Ambulatório de Hepatologia Pediátrica do Hospital das Clínicas da UFMG, com o diagnóstico de colangite esclerosante primária até a idade de 18 anos. O diagnóstico foi estabelecido segundo os critérios clínicos, laboratoriais, radiológicos e/ou histopatológicos. Foi realizada investigação para exclusão de outras doenças hepáticas crônicas e causas secundárias de colangite. A análise dos dados foi efetuada com os recursos estatísticos do software SPSS. As variáveis foram expressas por meio de médias, desvio-padrão, frequência absoluta e porcentagem. RESULTADOS: Vinte e um pacientes preencheram os critérios de inclusão. Houve predomínio no sexo masculino (3,2:1). A média de idade ao diagnóstico foi 6,7±3,9 anos. Cinco (23,8%) pacientes apresentavam doença inflamatória intestinal associada, sendo quatro casos de colite ulcerativa e um de colite indeterminada. Na apresentação, os sinais e sintomas são variados, em geral discretos. O sintoma mais frequente foi dor abdominal (47,6%), seguido menos frequentemente por icterícia (28,6%) e prurido (14,3%). Em 33,3% dos pacientes, o motivo de início da investigação foi alteração de enzimas em pacientes assintomáticos ou oligossintomáticos. Todos os pacientes exibiam aumento das enzimas hepáticas: aminotransferases, gama glutamiltransferase e fosfatase alcalina. Vinte pacientes apresentavam alterações em exame colangiográfico, compatíveis com colangite esclerosante primária; um paciente não apresentava alterações na colangiorressonância, mas apresentava alterações histopatológicas compatíveis com colangite de pequenos ductos. Fibrose hepática já estava presente em 60% dos 15 pacientes com biópsia à admissão; com cirrose estabelecida em quatro pacientes. 28,5% dos pacientes tiveram evolução desfavorável, com dois (9,5%) óbitos e quatro (19%) pacientes transplantados. CONCLUSÃO: Colangite esclerosante primária é uma doença rara na criança e no adolescente, cujo diagnóstico inicial pode ser atrasado ou passar despercebido, principalmente por apresentar manifestações clínicas inespecíficas ou cursar de forma assintomática. É frequente a associação com doença inflamatória intestinal. O prognóstico pode ser reservado com o avançar da doença, sendo o transplante hepático o tratamento definitivo.

PRIMARY SCLEROSING CHOLANGITIS IN CHILDREN AND ADOLESCENTS.

BACKGROUND: Primary sclerosing cholangitis is a rare disease, but its prevalence has been underestimated in children and adolescents due to broad variation in clinical presentation as well as diagnostic challenges in this life period. OBJECTIVE: To evaluate children and adolescents with primary sclerosing cholangitis and to describe their clinical, laboratorial, histopathological, and cholangiography conditions. METHODS: This is an observational descriptive research that took place from 2005 to 2016 and included all the patients seen in the Outpatient Unit for Pediatric Hepatology of Hospital das Clinicas of UFMG who had been diagnosed with primary sclerosing cholangitis before the age of 18. Diagnosis was established through clinical, laboratory, radiographic and/or histopathologic criteria. Other chronic liver diseases were excluded, as well as secondary causes of cholangitis. Data analysis used statistic resources in SPSS software. Variables were expressed as averages, standard deviation, absolute frequency, and percentage. RESULTS: Twenty-one patients fulfilled criteria to be included in the research sample. Male patients predominated (3.2:1) and average age at diagnosis was 6.7±3.9 years. Five (23.8%) patients had associated inflammatory bowel disease, four had ulcerative colitis and one indeterminate colitis. Signs and symptoms vary and are usually discrete at presentation. The most frequent symptom was abdominal pain (47.6%) followed less frequently by jaundice (28.6%) and itching (14.3%). The reason for medical investigation was asymptomatic or oligosymptomatic enzyme alterations in 33.3% of patients. All patients presented increased hepatic enzymes: aminotransferases, gamma glutamyl transferase, and alkaline phosphatase. Twenty patients had alterations compatible to primary sclerosing cholangitis in their cholangiography exam; one patient had no alterations at magnetic resonance cholangiography, but presented histopathologic alterations that were compatible to small duct cholangitis. Hepatic fibrosis was present in 60% of 15 patients who were biopsied upon admission; cirrhosis being present in four (26.7%) patients. A total of 28.5% of patients had unfavorable outcomes, including two (9.5%) deaths and four (19%) transplants. CONCLUSION: Primary sclerosing cholangitis is a rare disease in childhood and adolescence and its initial diagnosis may be delayed or overlooked due to asymptomatic or unspecific clinical manifestations. The association with inflammatory bowel disease is common. Prognosis may be unfavorable as the disease progresses and hepatic transplant is the definitive treatment.

Evaluation of endoscopic secondary prophylaxis in children and adolescents with esophageal varices / Avaliação da profilaxia secundária endoscópica em crianças e adolescentes com varizes de esôfago

ABSTRACT BACKGROUND Bleeding of esophageal varices is the main cause of morbidity and mortality in children and adults with portal hypertension and there are few studies involving secondary prophylaxis in children and adolescents. OBJECTIVE To evaluate the efficacy of endoscopic secondary prophylaxis in prevention of upper gastrointestinal bleeding in children and adolescents with esophageal varices. METHODS This is a prospective analysis of 85 patients less than 18 years of age with or without cirrhosis, with portal hypertension. Participants underwent endoscopic secondary prophylaxis with sclerotherapy or band ligation. Eradication of varices, incidence of rebleeding, number of endoscopic sessions required for eradication, incidence of developing gastric fundus varices and portal hypertensive gastropathy were evaluated. RESULTS Band ligation was performed in 34 (40%) patients and sclerotherapy in 51 (60%) patients. Esophageal varices were eradicated in 81.2%, after a median of four endoscopic sessions. Varices relapsed in 38 (55.1%) patients. Thirty-six (42.3%) patients experienced rebleeding, and it was more prevalent in the group that received sclerotherapy. Gastric varices and portal hypertensive gastropathy developed in 38.7% and 57.9% of patients, respectively. Patients undergoing band ligation showed lower rebleeding rates (26.5% vs 52.9%) and fewer sessions required for eradication of esophageal varices (3.5 vs 5). CONCLUSION Secondary prophylaxis was effective in eradicating esophageal varices and controlling new upper gastrointestinal bleeding episodes due to the rupture of esophageal varices. Band ligation seems that resulted in lower rebleeding rates and fewer sessions required to eradicate varices than did sclerotherapy.

RESUMO CONTEXTO Os episódios de sangramento das varizes esofágicas são a principal causa de morbidade e mortalidade em crianças e adultos com hipertensão porta e poucos são os estudos envolvendo a profilaxia secundária em crianças e adolescentes. OBJETIVO Avaliar a eficácia da profilaxia endoscópica secundária na prevenção de hemorragia digestiva alta em crianças e adolescentes com varizes de esôfago. MÉTODOS Estudo prospectivo com 85 pacientes menores de 18 anos com hipertensão porta, cirróticos e não cirróticos. A profilaxia secundária endoscópica foi realizada através de ligadura elástica ou escleroterapia. Foram avaliadas erradicação de varizes, incidência de ressangramento, número de sessões endoscópicas necessárias para a erradicação, incidência de surgimento de varizes gástricas e da gastropatia da hipertensão porta. RESULTADOS Ligadura elástica foi realizada em 34 (40%) pacientes e escleroterapia em 51 (60%). As varizes de esôfago foram erradicadas em 81,2% após mediana de quatro sessões endoscópicas. Foi observada recidiva de varizes de esôfago em 38 (55,1%) pacientes. Ressangramento por ruptura de varizes de esôfago ocorreu em 36 (42,3%) pacientes e foi mais prevalente no grupo submetido à escleroterapia. O surgimento de varizes gástricas e gastropatia da hipertensão porta ocorreram em 38,7% e 57,9% respectivamente. Os pacientes submetidos à ligadura elástica apresentaram taxas menores de ressangramento (26,5% vs 52,9%) e número menor de sessões necessárias para erradicação das varizes de esôfago (3,5 vs 5). CONCLUSÃO A profilaxia secundária endoscópica mostrou-se eficaz para erradicação de varizes de esôfago e evitar novos episódios de hemorragia digestiva alta secundária à ruptura de varizes de esôfago. A ligadura elástica endoscópica provavelmente apresenta menores taxas de ressangramento e número menor de sessões necessárias para erradicação das varizes de esôfago, quando comparada à escleroterapia.

Evaluation of endoscopic secondary prophylaxis in children and adolescents with esophageal varices.

BACKGROUND: - Bleeding of esophageal varices is the main cause of morbidity and mortality in children and adults with portal hypertension and there are few studies involving secondary prophylaxis in children and adolescents. OBJECTIVE: - To evaluate the efficacy of endoscopic secondary prophylaxis in prevention of upper gastrointestinal bleeding in children and adolescents with esophageal varices. METHODS: - This is a prospective analysis of 85 patients less than 18 years of age with or without cirrhosis, with portal hypertension. Participants underwent endoscopic secondary prophylaxis with sclerotherapy or band ligation. Eradication of varices, incidence of rebleeding, number of endoscopic sessions required for eradication, incidence of developing gastric fundus varices and portal hypertensive gastropathy were evaluated. RESULTS: - Band ligation was performed in 34 (40%) patients and sclerotherapy in 51 (60%) patients. Esophageal varices were eradicated in 81.2%, after a median of four endoscopic sessions. Varices relapsed in 38 (55.1%) patients. Thirty-six (42.3%) patients experienced rebleeding, and it was more prevalent in the group that received sclerotherapy. Gastric varices and portal hypertensive gastropathy developed in 38.7% and 57.9% of patients, respectively. Patients undergoing band ligation showed lower rebleeding rates (26.5% vs 52.9%) and fewer sessions required for eradication of esophageal varices (3.5 vs 5). CONCLUSION: - Secondary prophylaxis was effective in eradicating esophageal varices and controlling new upper gastrointestinal bleeding episodes due to the rupture of esophageal varices. Band ligation seems that resulted in lower rebleeding rates and fewer sessions required to eradicate varices than did sclerotherapy.

Evaluation of primary prophylaxis with propranolol and elastic band ligation in variceal bleeding in cirrhotic children and adolescents / Avaliação da profilaxia primária em crianças e adolescentes cirróticos com propranolol e ligadura elástica

ABSTRACT Background The efficacy of nonselective β-blocker and endoscopic procedures, such as endoscopic variceal ligation, as primary prophylaxis of variceal hemorrhage in cirrhotic adults was demonstrated by numerous controlled trials, but in pediatric population, few are the number of studies. Objective The objective of this study is to evaluate the primary prophylaxis with β-blocker in cirrhotic children and adolescents with portal hypertension. Methods This is a cohort study encompassing 26 cirrhotic patients. β-blocker prophylaxis was performed with propranolol. When contraindicated the use of β-blocker, or if side effects presents, the patients were referred to endoscopic therapy with band ligation. Patients were evaluated by endoscopy, and those who had varicose veins of medium and large caliber or reddish spots, regardless of the caliber of varices, received primary prophylaxis. Results Of the 26 patients evaluated, 9 (34.6%) had contraindications to the use of propranolol and were referred for endoscopic prophylaxis. Six (35.3%) of the 17 patients who received β-blocker (propranolol), had bled after a median follow-up time of 1.9 years. β-blockage dosage varied from 1 mg/kg/day to 3.1 mg/kg/day and seven (41.2%) patients had the propranolol suspended due to fail of the β-blockage or adverse effects, such as drowsiness, bronchospasm and hypotension. Patients who received endoscopic prophylaxis (elastic bandage) had no bleeding during the follow-up period. Conclusion All of the patients that had upper gastroinstestinal bleeding in this study were under propranolol prophylaxis. The use of propranolol showed a high number of contraindications and side effects, requiring referral to endoscopic prophylaxis. The endoscopic prophylaxis was effective in reducing episodes of bleeding.

RESUMO Contexto A eficácia dos beta-bloqueadores e de procedimentos endoscópicos como a ligadura elástica endoscópica para profilaxia primária de ruptura de varizes de esôfago em adultos cirróticos já foram demonstrados por inúmeros ensaios clínicos na população adulta, porém poucos são os estudos envolvendo a faixa etária pediátrica. Objetivo Avaliar a profilaxia primária com β-bloqueador em crianças e adolescentes cirróticos com hipertensão porta. Métodos Estudo de coorte envolvendo 26 pacientes cirróticos. O propranolol foi o β-bloqueador utilizado para a profilaxia. Quando contraindicado o uso de β-bloqueador, ou se efeitos colaterais presentes, os pacientes eram encaminhados para profilaxia endoscópica com ligadura elástica. Os pacientes foram avaliados por endoscopia, e naqueles que foram observadas varizes de médio e/ou grosso calibre ou presença de manchas avermelhadas nas varizes, independentemente do calibre das varizes, a profilaxia primária foi indicada. Resultados Dos 26 pacientes avaliados, 9 (34,6%) tinham contraindicações para o uso de propranolol e foram encaminhados para a profilaxia endoscópica. Seis (35,3%) dos 17 pacientes que receberam β-bloqueador (propranolol) apresentaram sangramento após mediana de tempo de acompanhamento de 1,9 anos. A dose de β-bloqueio variou de 1 mg/kg/dia a 3,1mg/kg/dia e em sete (41,2%) pacientes o propranolol foi suspenso por falha em atingir β-bloqueio ou presença de efeitos adversos, tais como sonolência, broncoespasmo e hipotensão. No grupo de pacientes que receberam a profilaxia endoscópica (ligadura elástica) não foi observado nenhum episódio de hemorragia digestiva alta durante o período de acompanhamento. Conclusão Todos os pacientes que apresentaram hemorragia digestiva alta no presente estudo estavam recebendo profilaxia com propranolol. Foi observado, ainda, elevado número de contraindicações e efeitos colaterais, com consequente encaminhamento para profilaxia endoscópica. A profilaxia endoscópica foi eficaz na redução de episódios de hemorragia digestiva alta.

The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood.

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.