RESUMO
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 JovemRESUMO
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
IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.
Assuntos
Colangite Esclerosante/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/sangue , Fígado/diagnóstico por imagem , Rituximab/uso terapêutico , Idoso , Biópsia , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/imunologia , Diagnóstico Diferencial , Humanos , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Fatores Imunológicos/uso terapêutico , Masculino , Tomografia por Emissão de PósitronsRESUMO
Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress.
Assuntos
Anticorpos/sangue , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Hepatopatias/complicações , Hepatopatias/imunologia , Doença Celíaca/imunologia , Colangite Esclerosante/complicações , Colangite Esclerosante/imunologia , Dieta Livre de Glúten , Glutens/efeitos adversos , Glutens/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Hepatite C/complicações , Hepatite C/imunologia , Hepatite Autoimune/complicações , Hepatite Autoimune/imunologia , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/imunologia , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/imunologia , Falência Hepática/complicações , Falência Hepática/imunologia , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/imunologiaRESUMO
BACKGROUND: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. METHODS: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. RESULTS: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. CONCLUSIONS: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.
Assuntos
Anticorpos Antinucleares/sangue , Artrite Reumatoide/imunologia , Colangite Esclerosante/imunologia , Hepatite Autoimune/imunologia , Cirrose Hepática Biliar/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Prolapso da Valva Mitral/imunologia , Miopia/imunologia , Fator Reumatoide/sangue , Dermatopatias/imunologia , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Autoantígenos/sangue , Autoantígenos/imunologia , Colangite Esclerosante/sangue , Colangite Esclerosante/complicações , Colangite Esclerosante/diagnóstico , Estudos Transversais , Feminino , Hepatite Autoimune/sangue , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Humanos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/diagnóstico , Testes de Função Hepática , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Prolapso da Valva Mitral/sangue , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/diagnóstico , Miopia/sangue , Miopia/complicações , Miopia/diagnóstico , Dermatopatias/sangue , Dermatopatias/complicações , Dermatopatias/diagnósticoRESUMO
INTRODUCTION: Primary sclerosing cholangitis (PSC) is an idiopathic hepatobiliary disorder associated with an increased risk for cholangiocarcinoma (CCA) and a median survival time of 12 years. Reliable predictors of CCA and other major adverse events in PSC are currently lacking. Recently, serum IgE was found to be associated with CCA in a Japanese cohort of PSC patients. Our aim in this study was to determine whether IgE levels predict time to CCA, liver transplantation, or death in a Western (USA-based) cohort of PSC patients. MATERIAL AND METHODS: Thirty-eight patients with PSC and IgE levels were identified and categorized into low or high IgE groups based on the sample median. Groups were compared with respect to clinical characteristics and adverse endpoint-free survival, and the association between IgE and endpoints was assessed with multivariate proportional-hazards models. RESULTS: The median sample age at PSC diagnosis was 41 years, and median serum IgE level was 47.6 kU/L. Low and high IgE groups differed significantly only with respect to IgG subclasses, which were higher among the latter (p < 0.05). There were no significant differences in composite endpoint-free (p = 0.83) or CCA-free survival (p = 0.20). In multivariate analyses, only Mayo PSC risk score and MELD score were significant predictors of endpoint-free survival (p < 0.05). CONCLUSIONS: Serum IgE level is associated with several IgG subclass levels but not time to CCA, liver transplantation, or death among PSC patients in a USA-based cohort. While Mayo PSC risk score and MELD score can predict these outcomes, more specific predictors of CCA are needed.
Assuntos
Neoplasias dos Ductos Biliares/imunologia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/imunologia , Colangite Esclerosante/imunologia , Imunoglobulina E/sangue , Transplante de Fígado , Adulto , Neoplasias dos Ductos Biliares/etiologia , Colangiocarcinoma/etiologia , Colangite Esclerosante/complicações , Colangite Esclerosante/mortalidade , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Doença Hepática Terminal , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
There is little detailed clinical information on recurrent primary sclerosing cholangitis (rPSC) after liver transplantation in children. Our purpose was to describe the characteristics of children who had experienced rPSC after liver transplantation so that we could identify potential risk factors for recurrence. Clinical information for pediatric patients undergoing transplantation for primary sclerosing cholangitis (PSC) was retrospectively reviewed, and variables related to the pretransplant diagnosis of PSC and posttransplant variables were abstracted. The studied variables included the following: cytomegalovirus/Epstein-Barr virus status, early/late rejection, induction regimen, immunosuppression in the first year, steroid-resistant rejection, diagnosis of inflammatory bowel disease, and human leukocyte antigen markers commonly associated with PSC. A diagnosis of rPSC was made on the basis of radiographic features, histology, or both. Twelve patients underwent liver transplantation for PSC between 1993 and 2012. Patients received tacrolimus for maintenance immunosuppression after induction with steroids (n = 6) or thymoglobulin (n = 6). Three patients were diagnosed with rPSC 44, 60, and 62 months after transplantation. A fourth patient underwent retransplantation for graft failure with features of both hepatic artery stenosis and rPSC. This patient had distinct histological features of rPSC in the second graft. Three of the 4 patients were 7 years old or younger at the diagnosis of PSC. The patient and graft survival rates were similar for the steroid and thymoglobulin groups. All 4 children with rPSC received steroid-free thymoglobulin induction. In conclusion, our observation of an association between thymoglobulin, and age less than 10 years at the diagnosis of PSC, and rPSC adds to the existing suggestion of a link between the immune environment and the pathogenesis of rPSC. Defining the natural history of rPSC and searching for the etiology and risk factors of rPSC are important for the long-term outcomes of pediatric patients.