Manejo clínico e obstétrico em gestantes portadoras de hepatite autoimune complicada pela plaquetopenia moderada ou grave / Clinical and obstetrical management of pregnant women with autoimmune hepatitis complicated by moderate or severe thrombocytopenia

OBJETIVO: O presente trabalho tem como objetivo descrever o manejo do pré-natal e do parto em pacientes portadoras de hepatite autoimune associada à plaquetopenia moderada ou grave. MÉTODOS: Este trabalho foi realizado em hospital universitário, de nível terciário. Foram analisadas, retrospectivamente, 13 gestações em dez pacientes com diagnóstico de hepatite autoimune complicadas pela plaquetopenia. Os critérios de inclusão foram: diagnóstico clínico de hepatite autoimune, plaquetopenia moderada ou grave (contagem de plaquetas < 100 x 103/mm3), idade gestacional ao nascimento acima de 22 semanas e pacientes acompanhadas por equipe especializada da instituição. As variáveis estudadas incluíram idade materna, paridade, os regimes de tratamento, contagem de plaquetas, exames para investigação da função hepática, tipo de parto, peso ao nascer e idade gestacional no momento do parto. RESULTADOS: A média da idade materna foi de 24,5 anos (DP = 5,3) e seis (50%) ocorreram em nulíparas. Durante a gravidez, a monoterapia com prednisona foi adotada em 11 (92%) casos. De acordo com o perfil de autoanticorpos, sete (58%) gestações possuíam diagnóstico de hepatite autoimune tipo I, duas (17%) do tipo II e três (25%) eram portadoras de hepatite crônica criptogênica (títulos de autoanticorpos indetectáveis). A hipertensão portal foi caracterizada em 11 (92%) gestações. A idade gestacional média no parto foi de 36,9 semanas (DP = 1,5 semana), com média de peso ao nascer de 2446g (DP = 655g), sendo oito (67%) pequenos para a idade gestacional. No momento do parto, a plaquetopenia grave foi caracterizada em quatro (33%) casos e a cesárea foi realizada em sete (58%). As complicações no parto ocorreram em três casos (25%), uma paciente apresentou atonia uterina e duas, hematoma perineal. Não houve morte materna ou perinatal. CONCLUSÃO: As complicações em pacientes plaquetopênicas com hepatite autoimune são elevadas, no entanto, com os cuidados e atenção necessários, podem ser contornáveis. A associação de duas patologias graves parece aumentar o risco de prematuridade e restrição do crescimento fetal, demandando atenção pré-natal especializada, bem como vigilância do bem-estar do concepto.

OBJECTIVE: To describe the management of prenatal care and delivery in patients bearing autoimmune hepatitis associated with moderate or severe thrombocytopenia. METHODS: This study was performed in a tertiary level university hospital. Thirteen pregnancies in ten patients diagnosed with autoimmune hepatitis, complicated by thrombocytopenia, were retrospectively analyzed. The inclusion criteria were as follows: clinical diagnosis of autoimmune hepatitis, moderate or severe thrombocytopenia (platelet count < 100 x 103/mm3), gestational age at birth over 22 weeks, and patient followed-up by a specialized team at the institution. The variables studied were: maternal age, parity, treatment regimen, platelet count, examinations for investigation of hepatic function, type of delivery, weight at birth, and gestational age at the time of delivery. RESULTS: The average maternal age was 24.5 years (SD = 5.3) and six (50%) occurred in nulliparous women. During pregnancy, monotherapy with prednisone was adopted in 11 cases (92%). According to the autoantibody profiles, seven pregnancies (58%) had the autoimmune hepatitis type I diagnosis, two pregnancies had type II (17%), and three pregnancies (25%) had cryptogenic chronic hepatitis (undetectable titers of autoantibodies). Portal hypertension was featured in 11 pregnancies (92%). The average gestational age at delivery was 36.9 weeks (SD = 1.5 weeks), with an average weight at birth of 2,446 g (SD = 655 g). Eight infants (67%) were small for gestational age. At the time of delivery, severe thrombocytopenia was featured in four cases (33%) and cesarean surgery was performed in seven cases (58%). Complications at delivery occurred in three cases (25%), one patient presented uterine atony, and two patients presented perineal bruising. There was no perinatal or maternal death. CONCLUSION: The complications of thrombocytopenic patients with autoimmune hepatitis are elevated; nevertheless, with appropriate attention and care, they can be resolved. The association between two severe pathologies appears to increase the risk of prematurity and fetal growth restriction, demanding specialized prenatal care, as well as surveillance of newborn well-being.

Research on zinc blood levels and nutritional status in adolescents with autoimmune hepatitis / Investigação do nível de zinco sanguíneo e estado nutricional em adolescentes com hepatite autoimune

CONTEXT: Zinc deficiency in children and adolescents impairs their growing, development and immune system. OBJECTIVE: To verify the existence of plasma and leukocyte zinc deficiency in adolescents with autoimmune hepatitis. METHODS: The study comprised 23 patients with autoimmune hepatitis, aged 10-18 years, assisted at the Ambulatory Service of Pediatric Hepatology of the University of Campinas Teaching Hospital, Campinas, SP, Brazil, and adolescents with ages compatible with the patients' ages comprised the control group. Sample of blood in both groups was collected for the analyses of plasma zinc and leukocyte zinc by atomic absorption spectrophotometry, beyond the nutritional status was evaluated in each adolescent. The following statistical tests were used: Mann-Whitney, Spearman's correlation and interclass concordance analysis. RESULTS:The significance level adopted was 5 percent. The average zinc level in plasma in patients was 71.91 ± 11.79 µg/dL and, in the control group, it was 80.74 ± 10.92 µg/dL, showing a significant difference (P = 0.04). The leukocyte zinc level in patients was 222.33 ± 166.13 pmol/10(6) cells and, in the control group, it was 226.64 ± 217.81 pmol/10(6) cells; there was no statistical significance between them (P = 0.45). CONCLUSION:The evaluation of the nutritional status showed that eutrophy is prevalent in patients, and they presented a higher body fat value than the control group, with a significant difference. More research is needed with adolescents with autoimmune hepatitis regarding levels of essential micronutrients, such as zinc, because a good nutritional status can improve the prognostic of liver disease.

CONTEXTO: A deficiência de zinco em crianças ou adolescentes acarreta danos ao crescimento, desenvolvimento e ao sistema imune dos indivíduos. OBJETIVO: Verificar a existência de deficiência de zinco plasmático e/ou leucocitário em adolescentes com hepatite autoimune. MÉTODOS:Participaram do estudo 23 pacientes com hepatite autoimune entre 10 e 18 anos, atendidos no Ambulatório de Hepatologia Pediátrica do Hospital de Clínicas da UNICAMP - Campinas, SP e 23 adolescentes com idade pareada com os pacientes formaram o grupo controle. Foi coletada amostra de sangue de todos os pacientes e grupo controle para as análises de zinco plasmático e zinco leucocitário por meio da espectrofotometria de absorção atômica, além de ter sido verificado o estado nutricional de cada adolescente. Os testes estatísticos empregados foram o de Mann-Whitney, correlação de Spearman e análise de concordância interclasses. RESULTADOS: O nível de significância adotado foi de 5 por cento. A média de zinco plasmático nos pacientes foi de 71.91 ± 11.79 µg/dL e no grupo controle foi de 80.74 ± 10.92 µg/dL, essa diferença foi significante (P = 0.04). O nível de zinco leucocitário nos pacientes foi igual a 222.33 ± 166.13 pmol/10(6) células e no grupo controle foi de 226.64 ± 217.81 pmol/10(6) células, não ocorrendo diferença estatisticamente significante entre estes (P = 0.45). CONCLUSÃO: A avaliação do estado nutricional mostrou que a eutrofia é prevalente nos pacientes e estes possuem maior valor de gordura corporal que o grupo controle com diferença significativa. São necessárias mais pesquisas com adolescentes com hepatite autoimune em relação aos níveis de micronutrientes essenciais, como o zinco, pois um bom estado nutricional pode melhorar o prognóstico da doença hepática.

Hepatitis autoinmune en niños: diagnostico / Autoimmune hepatitis in children: diagnosis

El diagnóstico de la hepatitis autoinmune (HAI), se basa en una serie de criterios definidos por elGrupo Internacional de HAI (IAIHG) que permite clasificarla como HAI probable o definitiva. Un criterio clave para el diagnóstico de la HAI es la detección de ANA, SMA, y anti- LKM-1 por inmunofluorescencia indirecta. Otros anticuerpos menos frecuentes probados, pero de importancia diagnóstica en HAI pediátrica incluyen los anticuerpos tipo: citosol 1 hígado (LC-1), anti- citoplasma de los neutrófilos (ANCA) y el antígeno soluble hepático (SLA). La Ig G está usualmente elevada en ambos tipos de HAI, cerca del 15% de niños con HAI I y el 25% de niños con HAI tipo II tienen valores normales. La biopsia hepática es necesaria para establecer el diagnóstico de HAI.

The diagnosis of autoimmune hepatitis (HAI), is based on a set of criteria defined by the International HAI Group (IAIHG) that allows classified as a probable or definite HAI. A key criterion for the diagnosis of HAI is the detection of ANA, SMA, and anti-LKM-1 by indirectimmunofluorescence. Other less common antibodies tested, but important diagnostic tool in pediatric HAI include antibodies such as: liver cytosol 1 (LC-1), anti-neutrophil cytoplasmic (ANCA) and soluble liver antigen (SLA). The Ig G is usually high in both types of HAI, about 15% of children with HAI I and 25% of children with HAI type II are normal. Liver biopsy is necessary to establish the diagnosis of HAI.

Elevated serum immunoglobulin G levels in patients with chronic liver disease in comparison to patients with autoimmune hepatitis

Hypergammaglobulinemia is frequently observed in patients with chronic liver disease [CLD] of different causes. On the other hand, elevated levels of serum immunoglobulin G [IgG] are the best diagnostic marker for autoimmune hepatitis [AIH]. Thus, the ability to distinguish AIH patients from patients with other liver disease, especially patients with advanced liver cirrhosis, is important since most AIH patients will a have favorable treatment response if diagnosed properly. We conducted this study to evaluate the significance of elevated IgG levels in patients with nonautoimmune CLD and to compare these IgG levels with those in patients with AIH upon diagnosis. Setting and study population: The serum IgG levels in 27 patients with AIH determined at the time of diagnosis were compared to the serum IgG levels in 27 patients with other CLDs of variable severity at the King Abdul Aziz University Hospital in Jeddah, Saudi Arabia. Severity of the disease was evaluated in all patients. We found that the patients in the CLD group with decompensated cirrhosis had significantly higher serum IgG levels compared to the compensated CLD patients [p<0.02]. In addition, the AIH patients had significantly higher serum IgG levels than the non-autoimmune hepatitis CLD patients and the decompensated cirrhosis patients in the CLD group [p<0.001 and p<0.044, respectively]. Most patients with elevated serum IgG of the AIH group [67%] and the CLD group [75%] had significant hypergammaglobulinemia, not just isolated elevated IgG levels. Elevated serum IgG levels with hypergammaglobulinemia are commonly found in patients with advanced CLD. The differentiation of such cases from AIH is important in order to avoid misdiagnosis and confusion with AIH

Nutritional status of patients with biliary atresia and autoimmune hepatitis related to serum levels of vitamins A, D and E / Estado nutricional de pacientes com atresia biliar e hepatite autoimune e relação com os níveis séricos de vitaminas A, D e E

CONTEXT: Chronic liver disease may induce to malabsorption of lipids and fat-soluble vitamins, leading to injury of nutritional status. OBJECTIVES: To evaluate the nutritional status of pediatric-age patients with autoimmune hepatitis and biliary atresia related to serum levels of vitamins A, D and E and the disease severity. METHODS: This controlled transverse study, evaluated the patients with autoimmune hepatitis and biliary atresia and a reference group paired by sex and age. The patients underwent anthropometric evaluation, alimentary inquiry and determination of serum levels of vitamins A, D and E by high performance liquid chromatography. The Mann-Whitney test, Spearman correlation coefficients and variance analysis (ANOVA) were utilized for data treatment, regarding significant difference if P<0.05. RESULTS: The highest nutritional deficit was observed in patients with biliary atresia, mainly with cholestasis. The serum levels of vitamins A and E for the reference group changed as a function of age. The serum levels of vitamins A, D and E were higher in reference group than in patients with biliary atresia and autoimmune hepatitis together or separately. There were not difference in the serum levels of vitamins A, D and E between biliary atresia groups with cholestasis and without cholestasis. It was verified correlation between weight/age, triceps skinfold thickness, subscapular skinfold thickness, midarm circumference, midarm fat area values and vitamin A serum levels, as well as between all anthropometric indicators and vitamin E in patients with autoimmune hepatitis and biliary atresia. CONCLUSION: The patients with biliary atresia and cholestasis presented the highest nutritional injury. The patients with biliary atresia and autoimmune hepatitis presented lower serum levels of vitamins A, D and E that in control group. There is a directly proportional correlation between vitamin serum levels, mainly vitamin E, and all anthropometric...

CONTEXTO: As doenças hepáticas crônicas podem induzir à má absorção de lipídios e vitaminas lipossolúveis e levar ao comprometimento do estado nutricional. OBJETIVOS: Avaliar o estado nutricional e relacionar com os níveis séricos de vitaminas (A, D e E) e a gravidade da doença em pacientes com atresia biliar e hepatite autoimune na faixa etária pediátrica. MÉTODOS: O estudo foi transversal controlado e foram avaliados os pacientes com hepatite autoimune e atresia biliar e um grupo controle pareado por sexo e idade. Foi realizada avaliação antropométrica, aplicação do inquérito alimentar e determinação dos níveis séricos das vitaminas A, D e E pela técnica de cromatografia líquida de alta eficiência. Foram empregados os testes de Mann-Whitney, o coeficiente de correlação de Spearman e análise de variância (ANOVA), sendo considerada diferença significativa se P<0,05. RESULTADOS: O déficit nutricional mais grave foi observado nos pacientes com atresia biliar, principalmente com colestase. Em relação às vitaminas, no grupo controle, constatou-se que os níveis séricos das vitaminas A e E variaram com a idade. Os níveis séricos das vitaminas A, D e E foram maiores no grupo controle em relação aos pacientes com atresia biliar e hepatite autoimune em conjunto ou separadamente. Verificou-se a correlação do peso/idade, prega cutânea tricipital, prega cutânea subescapular, circunferência braquial, área adiposa braquial com a vitamina A e de todos os indicadores antropométricos com a vitamina E nos pacientes com hepatite autoimune e atresia biliar em conjunto. CONCLUSÕES: Os pacientes com atresia biliar e colestase apresentaram o maior comprometimento nutricional. Os pacientes com atresia biliar e hepatite autoimune possuíram menores níveis séricos das vitaminas A, D e E do que o grupo controle. Existe uma correlação diretamente proporcional, principalmente da vitamina E com todos as variáveis antropométricas do grupo de AB e HAI em conjunto.

Autoimmune hepatitis.

Autoimmune hepatitis is one of the causes of chronic progressive liver disease in childhood. Here we report 14 cases with clinical findings, therapeutic management and prognosis, in order to define the course of the disease. Diagnosis of autoimmune hepatitis was done with the presence of at least one of these autoantibodies; antinuclear antibody, smooth muscle antibody, liver-kidney microsomal type 1 antibody, and perinuclear antineutrophilic cytoplasmic antibody. Patients were seen every 3 to 6 months. After doing a complete physical examination, biochemical parameters and autoantibodies determined at each visit. Mean age at diagnosis was 10.9 +/- 2.6 years (range, 7-15.5 years) and female to male ratio was 1:3. Thirteen patients had jaundice and all had high levels of ALT, AST and gammaglobulin. Hepatomegaly was found in 71.4% and splenomegaly in 64.3% of the patients. All patients were classified as type 1 autoimmune hepatitis. Liver biopsies revealed severe active hepatitis with mononuclear cell infiltration in portal areas, piecemeal necrosis. Drug therapy consisted of prednisone (2 mg/kg/day) per oral at the beginning, and addition of azathioprine (1.5 mg/kg/day) per oral at the 3rd-6th month with slow tapering of prednisone in 12 children. Both drugs were started together to two patients. Follow-up period was 30.7 +/- 15.6 months (range, 12-72 months). Sustained normalization of ALT could not be obtained with tapering doses of prednisone alone. Decrease in ALT levels did not correlate with disappearance of serum autoantibodies. None of the patients showed decompensation of liver disease. Azathioprine administration is necessary to decrease prednisone dose and to maintain a sustained normal transaminase values.