RESUMO
Autoimmune hepatitis (AIH) is a rare, chronic, inflammatory, and necrotic liver disease characterized by the presence of autoantibodies. Its etiology is unknown. It affects 1 in 200 000 people annually in the US and occurs predominantly in women. Its presentation varies from asymptomatic forms to cirrhosis and acute liver failure and its diagnosis is based on the measurement of autoantibodies, such as antinuclear autoantibodies (ANA), anti-smooth muscle antibodies (ASMA) and anti-liver and kidney microsomal antibodies (anti-LKM). 1). 10% of HAIs do not present antibodies, being called seronegative HAI, requiring a liver biopsy for diagnosis. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to carry out a bibliographic review on the subject, capturing in this document the important information for the understanding and management of this pathology.
La hepatitis autoinmune (HAI) es una enfermedad inflamatoria y necrótica del hígado, crónica e infrecuente caracterizada por la presencia de autoanticuerpos. Su etiología es desconocida. Afecta a 1 de cada 200 000 personas anualmente en los EE. UU. y se presenta predominantemente en mujeres. Su presentación varía desde formas asintomáticas hasta la cirrosis y falla hepática aguda y su diagnóstico se basa en la medición de autoanticuerpos, como los autoanticuerpos antinucleares (ANA), anticuerpos antimúsculo liso (ASMA) y anticuerpos antimicrosomales de hígado y riñón (anti-LKM-1). El 10% de las HAI no presentan anticuerpos, denominándose HAI seronegativa, necesitando biopsia hepática para el diagnóstico. Hasta la fecha la evidencia sigue siendo limitada y diferentes sociedades han emitido sugerencias y recomendaciones. Por tal motivo creemos relevante realizar una revisión bibliográfica sobre el tema plasmando en este documento la información importante para la compresión y el manejo de esta patología.
Assuntos
Autoanticorpos , Hepatite Autoimune , Humanos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Autoanticorpos/sangue , Feminino , Biópsia , MasculinoRESUMO
INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. Methods: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Autoanticorpos/sangue , Immunoblotting/métodos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Hepatite Autoimune/sangue , Hepatopatias/diagnóstico , Hepatopatias/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/sangue , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/sangueRESUMO
INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. METHODS: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.
Assuntos
Autoanticorpos , Hepatite Autoimune , Immunoblotting , Hepatopatias , Humanos , Feminino , Autoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Adulto Jovem , Immunoblotting/métodos , Hepatite Autoimune/imunologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/sangue , Hepatopatias/imunologia , Hepatopatias/diagnóstico , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/sangue , Doenças Autoimunes/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/sangueRESUMO
OBJECTIVES: To evaluate the prevalence and clinical significance of autoantibodies in children with overweight and obesity with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) compared with those with autoimmune liver disease (ALD). STUDY DESIGN: This was a retrospective, cross-sectional study of children with a biopsy-proven diagnosis of NAFL, NASH, autoimmune hepatitis (AIH), or primary sclerosing cholangitis (PSC) and a body mass index (BMI) >85th percentile treated between 2007 and 2016. RESULTS: A total of 181 patients were identified, including 31 (17%) with NAFL, 121 (67%) with NASH, 12 (6.6%) with ALD (AIH, PSC, or overlap), and 17 (9.4%) with combined ALD and NAFLD. Antinuclear antibody (ANA), anti-actin antibody, and anti-liver kidney microsomal (LKM) antibody were positive in 16.1%, 13.8%, and 0%, respectively, of the patients with NAFL and in 32.8%, 15.5%, and 0%, respectively, of those with NASH. Total immunoglobulin G (IgG) was elevated in 27.3% of the patients with NAFL and in 47.7% of those with NASH, but in 100% of those with ALD. The positive predictive value of LKM was 100% for ALD but only 29% for ANA and 46% for anti-actin antibody. CONCLUSIONS: False-positive rates of autoantibodies were higher in pediatric patients with overweight and obesity with NAFLD compared with the general adult population. Positive LKM had the highest specificity and positive predictive value, and elevated IgG level had the highest sensitivity for ALD. The presence of autoantibodies does not signal more severe NAFLD in children. BMI >98th percentile seems to be an important breakpoint above which ALD is less likely.
Assuntos
Autoanticorpos/sangue , Colangite Esclerosante/diagnóstico , Hepatite Autoimune/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade Infantil/complicações , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Colangite Esclerosante/sangue , Colangite Esclerosante/complicações , Colangite Esclerosante/imunologia , Regras de Decisão Clínica , Estudos Transversais , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Hepatite Autoimune/sangue , Hepatite Autoimune/complicações , Hepatite Autoimune/imunologia , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/imunologia , Gravidade do Paciente , Obesidade Infantil/sangue , Obesidade Infantil/imunologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemAssuntos
Hepatite Autoimune/diagnóstico , Hepatite Autoimune/história , Pré-Escolar , Diagnóstico Diferencial , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Hepatite Crônica/diagnóstico , Hepatite Crônica/história , Hepatite Crônica/imunologia , Hepatite Crônica/patologia , História do Século XX , História do Século XXI , Humanos , MasculinoRESUMO
Introducción. Las enfermedades autoinmunes del hígado son un grupo de patologías caracterizadas por una respuesta autoinmune contra los hepatocitos y/o el epitelio biliar. Sus manifestaciones clínicas son variadas, con alteraciones en las pruebas de función hepática y presencia de autoanticuerpos. Metodología. Estudio observacional descriptivo con 101 pacientes atendidos en el Hospital Universitario de La Samaritana de Bogotá D.C., entre enero a diciembre de 2019, con los diagnósticos de hepatitis autoinmune, colangitis biliar primaria, colangitis esclerosante primaria y síndrome de sobreposición. Se evaluaron los parámetros clínicos y de laboratorio, con el fin de caracterizar su frecuencia en estas patologías, debido a la importancia de un diagnóstico precoz. Resultados. Se encontraron 54 casos de hepatitis autoinmune, 19 casos de colangitis biliar primaria, 4 casos de colangitis esclerosante primaria y 24 casos de síndrome de sobreposición. El 81% fueron mujeres y la edad promedio fue de 55 años. El 39% de los pacientes tenían cirrosis. En general, los resultados se ajustaron a lo descrito internacionalmente, como es el predominio en mujeres y la comorbilidad autoinmune. Conclusión. Los hallazgos indican que cualquier alteración del perfil bioquímico hepático debe ser considerado, y se debe descartar la presencia de hepatopatías autoinmunes para diagnosticarlas de manera precoz, evitando que lleguen a cirrosis y sus complicaciones, con la necesidad de un trasplante hepático como única alternativa terapéutica.
Introduction. Autoimmune liver diseases are a group of pathologies characterized by an autoimmune response against hepatocytes and/or the biliary epithelium. Their clinical manifestations are varied, with alterations in liver function tests and the presence of autoantibodies. Methodology. Descriptive study with 101 patients who attended at the Hospital Universitario de La Samaritana in Bogota D.C., between January and December 2019, with the diagnoses of autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and overlap syndrome. Clinical and laboratory parameters were evaluated in order to characterize their frequency in these pathologies, due to the importance of an early diagnosis. Results. There were 54 cases of autoimmune hepatitis, 19 cases of primary biliary cholangitis, 4 cases of primary sclerosing cholangitis, and 24 cases of overlap syndrome. Of all patients, 81% were women, the average age was 55 years, and 39% had cirrhosis. In general, the findings were consistent with what has been described worldwide, such as a higher prevalence in women and autoimmune comorbidity. Conclusion. The findings indicate that any alteration in the liver biochemical profile should be considered to rule out an autoimmune liver disease for an early diagnosis, avoiding the possibility of cirrhosis and its complications, with the need for a liver transplant as the only therapeutic alternative.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Autoimunidade , Hepatopatias/imunologia , Autoanticorpos/sangue , Síndrome , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/imunologia , Estudos Retrospectivos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Octogenários , Transaminases/sangue , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/imunologia , Hepatopatias/diagnósticoRESUMO
In experimental autoimmune hepatitis (EAH) of Th1 profile, an extract of adult Ascaris suum worms (ASC) was previously found to deviate the immune response to a Th2/IL-10 pattern. Here, the effects of treatment with ASC on production of TGF-ß and the anti-Ascaris isotypes IgG1 and IgG2a in EAH were evaluated. EAH was induced in BALB/c mice, intravenously with concanavalin A. Two hours later, these animals received ASC (EAH+ASC group) or PBS vehicle (EAH group). IgG1 and IgG2a were evaluated 8 h, 24 h and 7 d after induction. TGF-ß was measured in a splenocyte culture at this last time. The isotype levels in the EAH group were low throughout the kinetics. In the EAH+ASC group, there was significant production of IgG1 at 24 h and 7 d, but of IgG2a only at 7 d. There was statistically greater production of TGF-ß in the EAH+ASC group. The higher levels of IgG1 and TGF-ß in this group suggest that an additional Th1 response control route exists in EAH, which needs to be investigated.
Assuntos
Ascaris suum/imunologia , Hepatite Autoimune/parasitologia , Imunoglobulina G/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Modelos Animais de Doenças , Hepatite Autoimune/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Chronic hepatitis C virus (HCV) infection and autoimmune disorders show a complex interplay, with HCV often being identified as the trigger of autoimmune phenomena or diseases. While there is evidence of successful HCV treatment with direct-acting antivirals (DAA) in patients with concomitant HCV and autoimmune hepatitis (AIH), there are also sparse reports of AIH developing during, or following, DAA treatment. Here we report a case of a patient with suspected concomitant HCV and AIH who underwent liver biopsy but showed no histological hallmarks of autoimmunity. The patient later developed a hepatitic flare following DAA-induced viral clearance, and a second liver biopsy showed features compatible with AIH. Response to corticosteroid and azathioprine treatment was seen. This reports demonstrates that patients with features of auto-reactivity and HCV after DAA-induced viral clearance require careful follow-up.
Assuntos
Hepatite C Crônica/complicações , Hepatite Autoimune/complicações , Actinas/imunologia , Idoso , Anticorpos Antinucleares/imunologia , Antivirais/uso terapêutico , Azatioprina/uso terapêutico , Biópsia , Carbamatos/uso terapêutico , Combinação de Medicamentos , Glucocorticoides/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Prednisolona/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
La hepatitis autoinmune es una enfermedad inflamatoria del hígado de etiología desconocida, que se caracteriza por la presencia de autoanticuerpos y niveles altos de globulinas séricas. Afecta a ambos sexos, a todos los grupos de edad, y se ha descrito en todas las razas. Tiene una amplia variedad de presentación clínica, lo que la convierte en un reto diagnóstico para el médico. La forma de presentación más común es la hepatitis aguda; sin embargo, un porcentaje no despreciable de pacientes es asintomático y hasta el 40% de los casos tiene cirrosis al momento del diagnóstico. El diagnóstico se basa en: 1) la medición de autoanticuerpos, como los antinucleares (ANA), los antimúsculo liso (ASMA), y los antimicrosomales de hígado y riñón (anti-LKM-1); 2) la detección de niveles séricos elevados de globulinas (especialmente IgG); 3) descartar otras etiologías de hepatitis crónica; y, 4) los hallazgos histológicos, los cuales además de confirmar el diagnóstico, ayudan a establecer la severidad. Se han desarrollado escalas y puntajes diagnósticos que permiten una mejor aproximación a dicha patología sin reemplazar el juicio del médico, por lo que deben ser interpretados bajo un adecuado contexto clínico. Un diagnóstico apropiado puede permitir el inicio oportuno de tratamiento con el fin de disminuir la progresión y el desarrollo de complicaciones.
Autoimmune hepatitis is an inflammatory disease of the liver of unknown etiology. It is characterized by the presence of autoantibodies and elevated levels of serum globulins. It affects both genders, all age groups and has been described in all races. It has a wide variety of clinical manifestations, so it remains a diagnostic challenge for physicians. The most common form of manifestation is acute hepatitis, however a non-negligible percentage of patients is asymptomatic, and up to 40% of cases have cirrhosis at the time of diagnosis. The diagnosis is based on: 1) measurement of autoantibodies, such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and liver/kidney microsomal type 1 antibodies (anti-LKM-1); 2) detection of elevated serum levels of globulins (especially IgG); 3) exclusion of other causes of chronic hepatitis; and, 4) histological findings, which also confirm the diagnosis and help determine its severity. Diagnostic scales and scores have been developed to allow a better approach to this pathology without replacing the clinical judgment, so they must be interpreted under an adequate clinical context. A proper diagnosis can allow a timely initiation of treatment in order to decrease the progression and the development of complications.
Assuntos
Humanos , Masculino , Feminino , Hepatite Autoimune/diagnóstico , Autoanticorpos/isolamento & purificação , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Cirrose Hepática/diagnósticoRESUMO
Abstract In experimental autoimmune hepatitis (EAH) of Th1 profile, an extract of adult Ascaris suum worms (ASC) was previously found to deviate the immune response to a Th2/IL-10 pattern. Here, the effects of treatment with ASC on production of TGF-β and the anti-Ascaris isotypes IgG1 and IgG2a in EAH were evaluated. EAH was induced in BALB/c mice, intravenously with concanavalin A. Two hours later, these animals received ASC (EAH+ASC group) or PBS vehicle (EAH group). IgG1 and IgG2a were evaluated 8 h, 24 h and 7 d after induction. TGF-β was measured in a splenocyte culture at this last time. The isotype levels in the EAH group were low throughout the kinetics. In the EAH+ASC group, there was significant production of IgG1 at 24 h and 7 d, but of IgG2a only at 7 d. There was statistically greater production of TGF-β in the EAH+ASC group. The higher levels of IgG1 and TGF-β in this group suggest that an additional Th1 response control route exists in EAH, which needs to be investigated.
Resumo Na hepatite autoimune experimental (HAE) de perfil Th1, o extrato de vermes adultos Ascaris suum (ASC) desviou a resposta imune para um padrão Th2/IL-10. Neste trabalho, foram avaliados os efeitos do tratamento com ASC na produção TGF-β e dos isótipos de IgG1 e IgG2a anti-Ascaris na HAE. Esta foi induzida em camundongos BALB/c intravenosamente com Concanavalina A. Após duas horas, os animais receberam ASC (grupo HAE+ASC) ou veículo PBS (grupo HAE). IgG1 e IgG2a foram avaliados em 8 horas, 24 horas e 7 dias após indução. TGF-β foi mensurado em cultura de esplenócitos nesse último tempo. Os níveis dos isótipos no grupo HAE foram baixos durante toda a cinética. No grupo HAE+ASC, houve produção significativa de IgG1 em 24 horas e 7 dias, mas somente em 7 dias para IgG2a. A produção de TGF-β foi estatisticamente maior no grupo HAE+ASC. Níveis mais altos de IgG1 e TGF-β nesse grupo sugerem uma via adicional de controle da resposta Th1 na HAE que precisa ser investigada.