¿Pensar en hepatitis autoinmune precozmente evita la cirrosis? / Does early autoimmune hepatitis diagnose prevent from cirrhosis?

La hepatitis autoinmune (HAI) es una hepatopatía inflamatoria crónica y progresiva, que afecta predominantemente al sexo femenino y se caracteriza por la presencia de autoanticuerpos, elevación de aminotransferasas e hipergammaglobulinemia. Evoluciona rápidamente a cirrosis en pacientes no tratados, por lo que su diagnóstico precoz es indispensable. El propósito de este estudio es evaluar el tiempo promedio entre el inicio de los síntomas y el diagnóstico, así como su correlación con la presencia de cirrosis. Se realizó un estudio analítico, retrospectivo, no experimental. Se revisaron las historias clínicas de 51 pacientes que acudieron a la consulta de gastroenterología del hospital de niños J.M. de los Ríos desde abril de 1996 hasta septiembre de 2010 diagnosticados de HAI según criterios clínicos, serológicos e histológicos. Se excluyeron 3 pacientes por presentar patologías asociadas o estar recibiendo tratamiento inmunosupresor previo. La edad varió entre 2 y 15 años (media 8,3±3,2 DE); prevaleciendo el sexo femenino (72,9%). La clínica predominante fue ictericia (81,3%), coluria (47,9%) y dolor abdominal (39,5%). El diagnóstico se realizó en promedio 8,4 ± 7,3 meses luego del inicio de los síntomas. 50% se diagnosticó en los primeros 6 meses, de éstos 54,2% presentó cirrosis y 33,3% fibrosis. La HAI debe considerarse en pacientes pediátricos con clínica de hepatopatía inflamatoria a fin de realizar un diagnóstico oportuno y precoz debido a su rápida evolución a cirrosis

Autoimmune hepatitis (HAI) is a progressive chronic inflammatory hepatopathy with higher prevalence in females characterized by autoantibodies presence, elevation of aminotransferases and hipergammaglobulinemia. Another important characteristic is that it can develop into a rapid cirrhosis, so early diagnosis is vital. The purpose of our study is to evaluate the time spent between initial symptoms and final diagnosis, and it relation with the presence of cirrhosis. An analytic, retrospective non experimental study was performed. We reviewed the clinical records of 51 patients from April 1996 to September 2010 who attended the consultation of gastroenterology in the J. M. de los Ríos Children's Hospital with the diagnose of HAI according to clinical criteria, serological and histological. We excluded 3 patients for two reasons. 1. They were presenting associated pathologies 2. They were receiving immunosuppressive treatment. The ages vary from 2 to 15 years old (mean 8.3±3.2 ED); female prevail with (72.9%). The predominant symptoms were jaundice (81.3%), coluria (47.9%) and abdominal pain (39.5%). The diagnosis was made on average 8.4 ± 7.3 months after the beginning of the symptoms. 50% were diagnosed in the first 6 months, from these 54.2% presented with cirrhosis and 33,3% with fibrosis. HAI must be considered in pediatric patients with inflammatory hepatopathy clinical history in order to make an early and opportune diagnosis due to its rapid evolution to cirrhosis

Hepatitis autoinmune en niños: clínica y manejo / Autoimmune hepatitis in children: clinical and management

La hepatitis autoinmune (HAI), es una enfermedad inflamatoria crónica y progresiva, que se caracteriza histológicamente por un denso infiltrado de células mononucleares en vías portales, y cuya patogenia se le atribuye a una reacción inmune frente a autoantígenos hepatocelulares demostrado serológicamente por la presencia de autoanticuerpos específicos y aumento en los niveles de las aminotransferasas y de inmunoglobulina tipo IgG, en ausencia de una etiología conocida. Son reconocidos dos tipos de HAI en la infancia: HAI tipo I, que se caracteriza por la presencia de anticuerpos (anti músculo liso SMA) y/o antinucleares (ANA), y la HAI tipo II,que se caracteriza por anticuerpos antimicrosomales de riñón hígado (anti-LKM). La etiología de la HAI es desconocida, aunque tanto factores genéticos como ambientales están implicados en su expresión. El fenotipo clínico de la HAI en niños varía en gran medida, va desde una evolución leve a un curso fulminante. La HAI es sensible a la terapia inmunosupresora. El trasplante hepático está indicado en pacientes que presentan insuficiencia hepática fulminante (encefalopatía) y los que desarrollan enfermedad hepática terminal.

Autoimmune hepatitis (HAI) is a chronic and progressive inflammatory disease, characterizedhistologically by a dense infiltrate of mononuclear cells in the process portals, and whose pathogenesis is attributed to an immune response against hepatocellular autoantigens demonstratedserologically by the presence of specific autoant ibodies and increased levels of aminotransferases and immunoglobulin IgG, in the absence of known etiology. Recognized two types of HAI in childhood: type I, characterized by the presence of antibodies (smooth muscle anti SMA) and / or antinuclear (ANA) and type II, characterized by anti-microsomal antibodies liver kidney (anti-LKM). The etiology of HAI is unknown, a l though both gene t i c and environmental factors are involved in its expression. The clinical phenotype of the HAI in children varies greatly, ranging from a slight evolution to a fulminant course. The HAI is sensitive to immunosuppressive therapy. Liver transplantation is indicated in patients with fulminant hepatic failure (encephalopathy) andthose who develop end-stage liver disease.

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.

Recurrencia de la enfermedad hepática primaria después del trasplante hepático / Liver disease recurrence after liver transplantation

Liver transplantation has become a standard option in the management of patients with end-stage liver disease. It is now evident that the most common etiology of long-term graft dysfunction is the recurrence of the primary liver disease. Autoimmune liver disorders such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis recur between 15 to 30 percent of the graft recipients. The clinical expression of this recurrence tends to be milder; the diagnosis is only established in many patients by fndings in the liver biopsy. This milder clinical expression may be due to the use of immunosuppressive therapy for the prevention of organ rejection and it may also be modulating immune mechanisms that underlie these conditions. The recurrence of hepatitis C virus infection is characterized by an accelerated progression towards cirrhosis and hepatic failure due to the lack of an effective immunoprophylaxis program and an effective antiviral therapy. The recurrence of hepatitis B is uncommon due to the availability on an effective immunoprophylaxis program with effective antiviral agents. The familial amyloidotic polyneuropathy is a genetic condition residing in the hepatocyte that produces a mutation of transthyretin; this abnormal protein is deposited in peripheral nerves, gastrointestinal tract, heart, and kidneys. The liver from these patients, apart from producing this abnormal protein, is otherwise normal, and has been used as an organ for recipients in dire need of a liver transplant, such as patients with hepatocellular carcinoma. This approach is known as “domino” liver transplantation. As these recipients are followed long term, they may develop de novo amyloidosis. In summary, the underlying liver condition that led to endstage liver disease and liver transplantation may recur after liver transplantation. The clinical expression of the recurrence of the hepatic disease is modulated by the immunosuppression...

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)...