Avaliação de pacientes com hepatite autoimune atendidos em ambulatório de referência do sul do Brasil / Evaluation of patients with autoimmune hepatitis in a specialized outpatient clinic in southern brazil

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by necroinflammation and autoimmune etiology. Studies evaluating the characteristics of patients with AIH are scarce in Brazil. OBJECTIVE: Our objective was to evaluate the profile of patients with AIH in a specialized center in Southern Brazil and to verify factors related to treatment response. METHODS: this was a retrospective cohort study, which analyzed demographic, epidemiological, clinical, laboratory, and histologic data. Patients with AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (IAIHG) were included. In liver biopsies, the degree of fibrosis, histological activity, presence of hepatocyte rosettes, plasma cell infiltrates, and confluent necrosis were evaluated. In the statistical analysis, the significance level was 5%. RESULTS: Forty adults patients diagnosed with AIH were included. The evaluated population predominantly consisted of women (75.0%) and the average age at diagnosis was 44.2 years. The association with extrahepatic autoimmune diseases occurred in 20.0% of cases. Clinically, 35.0% of patients presented with acute onset hepatitis, 37.5% with cirrhosis, and 27.5% with other forms of presentation. The most common clinical manifestation was jaundice (47.5%). Thirty-five patients were treated, and of these, 97.1% used prednisone combined with azathioprine. The average treatment time was 2.7 years. Response to treatment was complete or partial in 30 (85.7%) and absent in 5 (14.3%) patients. There was no statistically significant difference when evaluating response to treatment in relation to forms of presentation, histological findings, and the presence of autoantibodies. Regarding fibrosis, regression was observed in 18.75% of the cases. CONCLUSION: Most patients with AIH were young at presentation and of female sex. The association with extrahepatic autoimmune diseases and cirrhosis at presentation was seen in a considerable proportion of patients. Treatment was effective, but there were no clinical, histological or serological parameters capable of predicting treatment response.

RESUMO CONTEXTO: A hepatite autoimune (HAI) é uma doença hepática crônica, de caráter necroinflamatório e etiologia autoimune. Os estudos que avaliam as características de pacientes com HAI são escassos no Brasil. OBJETIVO: Nosso objetivo foi avaliar o perfil dos pacientes com HAI atendidos em um centro de referência do sul do Brasil e verificar fatores relacionados à resposta ao tratamento. MÉTODOS: Este foi um estudo de coorte retrospectivo, que analisou dados demográficos, epidemiológicos e clínicos. Nas biópsias hepáticas, foram avaliados o grau de fibrose, a atividade histológica, a presença de rosetas, de infiltrado plasmocitário e de necrose confluente. Na análise estatística, o nível de significância foi de 5%. RESULTADOS: Foram incluídos 40 pacientes adultos com diagnóstico de HAI. Houve predomínio do sexo feminino (75,0%), e a média de idade no diagnóstico foi de 44,2 anos. A associação com doenças autoimunes extra-hepáticas ocorreu em 20,0% dos casos. Clinicamente, 35,0% dos pacientes se apresentaram sob forma de hepatite aguda, 37,5% com cirrose e 27,5% com outras formas de apresentação. A manifestação clínica mais comum na apresentação foi a icterícia (47,5%). Trinta e cinco pacientes foram tratados, sendo que destes, 97,1% utilizaram prednisona associada com azatioprina. A média do tempo de tratamento foi 2,7 anos. A resposta ao tratamento foi completa ou parcial em 30 (85,7%) e ausente em 5 (14,3%) pacientes. Não houve diferença estatisticamente significativa quando avaliada a resposta ao tratamento em relação à forma de apresentação, aos achados histológicos e à presença de autoanticorpos. Em relação à fibrose, foi observada regressão em 18,75% dos casos. CONCLUSÃO: A maioria dos pacientes era jovem no momento do diagnóstico e do sexo feminino. A associação com doenças autoimunes extra-hepáticas e com cirrose na apresentação foi vista em uma parcela considerável dos casos. O tratamento foi eficaz, mas não houve parâmetros clínicos, histológicos ou sorológicos capazes de prever a resposta ao tratamento.

Analysis of clinical features and prognosis in patients with primary Sjögren's syndrome and autoimmune liver disease / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical features and prognosis in patients with primary Sjögren's syndrome (pSS) and autoimmune liver diseases (ALD).@*METHODS@#A retrospective analysis of clinical manifestation and prognosis was performed in patients with ALD or without ALD during the three years (February 2014 to December 2017).@*RESULTS@#Totally, 203 patients with pSS were included in this study, 68 patients had ALD (31 patients with autoimmune hepatitis, 37 patients with primary biliary cholangitis), while 135 patients did not have ALD. There were no differences between the two groups regarding age, gender, clinical manifestations, such as dry mouth, dry eyes, pain, fatigue, lymphadenopathy, glandular swelling, cutaneous involvement, lung involvement, and renal involvement, and the incidence rate of other autoimmune diseases, such as autoimmune thyroid disease, rheumatoid arthritis, and vasculitis. There were also no differences in the titer of antinuclear antibody (ANA), the positive rates of anti-Sjögren's syndrome A antibody (SSA), SSA52, and anti-Sjögren's syndrome B antibody (SSB), and at the levels of erythrocyte sedimentation rate and C-reactive protein between the two groups. Most importantly, the pSS patients with ALD had a shorter disease course, a higher positive rate of anti-mitochondrial M2 antibody (AMA-M2) and anti-centromere antibody, a higher level of IgG and IgM, a lower level of complement 3, and a decreased number of blood cells. They also had a higher level of liver related serum index, such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase and total bilirubin, direct bilirubin, indirect bilirubin, a higher incidence rate of liver cirrhosis, an increased death incident (the mortality was 13.24% in the pSS patients with ALD, while 2.96% in the controls, P=0.013), and a worse prognosis. Binary Logistic regression analysis revealed that liver cirrhosis, the EULAR Sjögren's syndrome disease activity index (ESSDAI) scores and the level of total bilirubin were the prognostic factors of mortality in the pSS patients with ALD. The survival curve was estimated by the Kaplan-Meier method. It demonstrated that the pSS patients with ALD had a lower survival rate when compared with the controls.@*CONCLUSION@#The patients with both pSS and ALD will suffer from a more severe disease and a higher death incident. We should pay more attention to these patients and provide a better symptomatic treatment for them during clinical practice.

Hepatitis autoinmune en la edad pediátrica / Autoimmune hepatitis in the pediatric age

Resumen: En pediatría, la hepatitis autoinmune y la colangitis esclerosante son patologías de afección hepática cuyo mecanismo de daño es inmunológico. La hepatitis autoinmune es una enfermedad de etiología desconocida, caracterizada por hepatitis de interfase, hipergammaglobulinemia, autoanticuerpos circulantes y una respuesta favorable a la inmunosupresión. Es una enfermedad eminentemente pediátrica, con una afección prevalente hacia mujeres jóvenes. La terapia debe ser instituida con prontitud para prevenir el deterioro rápido, promover la remisión de la enfermedad y la supervivencia a largo plazo. La falta persistente de respuesta o la falta de adherencia al tratamiento dan como resultado una enfermedad hepática terminal. Los pacientes que desarrollan esta patología, y aquellos con insuficiencia hepática fulminante en el momento del diagnóstico, requerirán trasplante hepático.

Abstract: In pediatrics, autoimmune hepatitis and sclerosing cholangitis are liver disorders with an immunological damage mechanism. Autoimmune hepatitis is a disease of unknown etiology characterized by interface hepatitis, hypergammaglobulinemia, circulating autoantibodies and a favorable response to immunosuppression. It is an eminently pediatric disease with a prevalent condition in young women. Therapy should be instituted promptly to prevent rapid deterioration, promote remission of disease and long-term survival. The persistent lack of response or lack of adherence to treatment results in terminal liver failure; these patients, and those with fulminant hepatic insufficiency at the time of diagnosis, will require liver transplantation.

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.

Estudo de prevalência de auto-anticorpos não órgão específicos em população rural do nordeste brasileiro (Cavunge-Ba) / Study of the prevalence of autoantibodies not specific national rural population of Northeast Brazil (Cavunge-Ba)

Os auto-anticorpos hepáticos (AAH), incluindo os anticorpos antinúcleo (ANA), antimúsculo liso (SMA), antimicrossoma de fígado e rim do tipo 1 (anti-M1), anticitosol hepático do tipo 1 (anti-LC1) e antimitocôndria (AMA), podem ser encontrados em 1 por cento a 43 por cento dos indivíduos saudáveis, sendo considerados auto-anticorpos naturais. Por outro lado, são também considerados marcadores de enfermidades auto-imunes, particularmente hepatite auto-imune (HAI) e cirrose biliar primária (CBP), duas doenças auto-imunes do fígado de prevalência ainda desconhecida na população brasileira. Com o intuito de avaliar a freqüência de AAH na população normal e sua correlação com estado de doença e de investigar a prevalência de HAI e CBP no Brasil, foram coletadas amostras de soro de 725 indivíduos, aleatoriamente selecionados, residentes no povoado de Cavunge para realização de AAH por imunofluorescência indireta (IFI), empregando cortes de roedores, fibroblastos e células Hep-2. Os resultados foram comparados com dados demográficos e marcadores sorológicos de infecção por vírus A, B e C. Positividade para AAH foi considerada na presença de titulação igualou superior a 1:40, sendo considerada clinicamente relevante titulação igualou superior a 1:80. Cento e um indivíduos (14 por cento) apresentaram reatividade para AAH, a maioria com títulos de 1:40, sendo observada positividade para SMA, ANA e AMA em respectivamente 10 por cento, 4 por cento e 0,1 por cento dos indivíduos. Não foi encontrada reatividade para anti-LKM 1 e anti-LC 1. Os principais padrões de IFI para SMA e ANA foram, respectivamente, vaso e glomérulo I e nuclear pontilhado grosso. Apenas um indivíduo com SMA exibiu reatividade para anti-microfilamento em baixo título, não sendo observado...

[Overlap syndrome autoimmune hepatitis=primary biliary cirrhosis. Comparative study with isolated autoimmune hepatitis results of a multicentric Tunisian]

Autoimmune hepatitis [AIR] and primary biliary cirrhosis [PBC] are two autoimmune diseases affecting the liver. Suggestive signs of the two diseases can however occur simultaneously or consecutively in the same patient leading to an overlap syndrome. The aim of our multicentric retrospective study was to study clinical, biological, immunological and histological features of 17 patients with overlap syndrome and to compare them with those of 62 patients with isolated autoimmune hepatitis. Overlap syndrome "AIH-PBC" accounts for 20,5%of patients with autoimmune hepatitis in our series. Our two groups were similar in age and gender. Clinically, in overlap syndrome group, a significantly higher prevalence of pruritus arid significantly lower prevalence of ascites were observed as compared to isolated AIH group. No significant differences were observed between the two groups of patients with regard to frequency of concurrent immune diseases. Biologically, serum alkaline phosphatase and garnma-glutamyl-transpeptidase were significantly higher in overlap syndrome than in patients with isolated AIH. Significantly more overlap syndrome patients were positive for anti-mitochondrial antibodies than isolated AIR patients. The patients with isolated AIR had a higher frequency of cirrhosis at presentation that the patients with overlap syndrome. The histologic profile was not different between isolated AIR and Overlap syndrome. Overlap syndrome "AIR-PBC" is not rare. Compared with isolated AIH, it is characterised by a higher frequency of clinical and biological signs of cholestasis, a higher frequency of antimitochondrial antibodies and the rarity of cirrhosis at the diagnosis of the disease

Association between HLA class II alleles and autoimmune hepatitis type 1 in Thai patients.

OBJECTIVE: To investigate the association between HLA class II alleles and autoimmune hepatitis (AIH) type I in Thai patients. MATERIAL AND METHOD: The clinical data of 50 autoimmune hepatitis patients type I (AIH) at Siriraj hepatitis clinic were analysed, 37 of whom were tested for HLA class II genotyping using polymerase chain reaction and sequence-specific oligonucleotide technique (PCR-SSO). RESULTS: AIH is an uncommon chronic hepatitis in Thailand with females predominant. The HLA DRB1*0301, and DQA1*0101 were significantly associated with AIH patients when compared to controls; (OR = 3.92 [1.18-13.30], p 0.021, OR = 2.31 [1.13-4.73], p 0.019, respectively). When 18 patients with "definite" AIH were analysed, only HLA DRB1*0301 was still significantly associated with AIH (OR = 5.22, 95%CI = 1.28-20.92, p 0.015). CONCLUSION: HLA genotyping has shown that HLA DRB1*0301 and HLA DQA1*0101 were significantly associated with AIH.

Associação dos antígenos HLA-DR e DQ com a hepatite auto-imune tipos 1 e 2 / Association of HLA-DR and DQ with autoimmune hepatitis types 1 and 2

A susceptibilidade genética à hepatite auto-imune tipo 1 (HAI-1) foi associada aos antígenos de HLA-DR3, DR52 e DR4 em pacientes europeus e norte­ americanos, ao HLA-DR4 no Japão e aos HLA-DR4 e DR13 na América Latina. A predisposição à HAI-1 não foi estudada em outros grupos étnicos e poucos estudos avaliaram pacientes com hepatite auto-imune tipo 2 (HAI-2). O objetivo deste estudo foi investigar a associação dos HLA-DR e DQ em pacientes brasileiros com HAI-1 e HAI-2 e comparar as freqüências desses antígenos com parâmetros clínicos e laboratoriais da doença e com a resposta ao tratamento. A determinação de HLA-DRB e DQB1 foi realizada por PCR-SSP em 143 pacientes e em 126 indivíduos saudáveis. Cento e quinze pacientes apresentaram HAI-1 com reatividade para anticorpo anti-actina (AAA) elou anticorpo antinúcleo (AAN)...

Hepatite autoimune entre hepatopatas crônicos de um hospital geral, Belém-PA / Autoimmune hepatitis within the chronic liver diseases of the Hospital Geral, Belém-Pa

A hepatite Autoimune (HAI) é uma doença hepática infreqüente, porém seu diagnóstico preciso e precoce permite uma melhora substancial no prognóstico dos pacientes acometidos desta enfermidade. Objetivando encontrar a taxa de incidência de HAI entre os hapatopatas crônicos atendidos no programa de hepatopatias do Hospital da FSCMP, foram avaliados 459 pacientes no período de janeiro de 1993 a julho de 1998, sendo diagnosticados 12 (2,6 por cento) como portadores de HAI, sendo 11 do sexo feminino. A idade média era de 20,7 anos, em duas pacientes havia o antecedente de hepatite viral aguda A precedendo o quadro. A icterícia foi vista em 91 por cento (11/12) dos casos e a hepatomegalia esteve presente em 50 por cento (6/12) pacientes. Cinco já possuiam varizes esofagianas. Em 50 por cento (4/8), os auto-anticorpos encontrados foram a ANA e/ou AML. O histopalógico demonstrava hepatite crônica com atividade severa, sendo em seis com evoluçäo cirrogênica. Em 9/12 (75 por cento) o sistema de "score" era superior ou igual a 15 pontos, portanto com diagnóstico definitivo antes do tratamento. Conclui-se que neste estudo, a HAI corresponte a uma pequena parcela das etiologias de doença hepática em nosso meio, mais relacionada a mulheres jovens, do tipo 1, forma clássica, e em 51 por cento (6/11) observou-se uma atividade histológica grave com evoluçäo para cirrose hepática