RESUMO
INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.
Assuntos
Hepatite Autoimune , Imunossupressores , Humanos , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/sangue , Hepatite Autoimune/mortalidade , Hepatite Autoimune/patologia , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Imunossupressores/uso terapêutico , Prognóstico , Brasil/epidemiologia , Resultado do Tratamento , Transplante de Fígado , Cirrose Hepática/mortalidade , Recidiva , Aspartato Aminotransferases/sangue , Alanina Transaminase/sangue , Indução de Remissão , Biomarcadores/sangue , Adulto Jovem , Ascite/etiologia , IdosoRESUMO
INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.
Assuntos
Hepatite Autoimune , Cirrose Hepática , Nomogramas , Valor Preditivo dos Testes , Curva ROC , Humanos , Hepatite Autoimune/complicações , Hepatite Autoimune/sangue , Hepatite Autoimune/diagnóstico , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Contagem de Plaquetas , Modelos Logísticos , Fatores de Risco , Reprodutibilidade dos Testes , China/epidemiologia , Técnicas de Apoio para a Decisão , Área Sob a Curva , Fatores Etários , Biomarcadores/sangue , Estudos Retrospectivos , Adulto Jovem , Povo Asiático , Idoso , População do Leste AsiáticoRESUMO
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 JovemRESUMO
INTRODUCTION AND OBJECTIVES: Hepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis. MATERIALS AND METHODS: Liver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease. RESULTS: In 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1-5×, 5-10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62-0.66), 0.72 (0.71-0.73), 0.80 (0.77-0.82) and 1.15 (1.0-1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1-5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93-1.63), 2.47 (2.13-2.70) and 4.57 (3.27-5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%). CONCLUSIONS: These data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.
Assuntos
Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Hepatopatias/sangue , Adulto , Colangite Esclerosante/sangue , Colangite Esclerosante/diagnóstico , Diagnóstico Diferencial , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite Autoimune/sangue , Hepatite Autoimune/diagnóstico , Humanos , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/diagnóstico , Hepatopatias/diagnóstico , Hepatopatias Alcoólicas/sangue , Hepatopatias Alcoólicas/diagnóstico , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnósticoRESUMO
Current guidelines recommend steroids for induction of remission in all children diagnosed with autoimmune hepatitis regardless of the clinical presentation. In this report, we describe our experience in treating selected asymptomatic children with autoimmune hepatitis using a steroid-free regimen; this treatment strategy was safe and effective in inducing remission.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Azatioprina/uso terapêutico , Hepatite Autoimune/terapia , Fígado/patologia , Indução de Remissão/métodos , Adolescente , Alanina Transaminase/sangue , Biomarcadores/sangue , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Glucocorticoides/farmacologia , Hepatite Autoimune/sangue , Hepatite Autoimune/diagnóstico , Humanos , Masculino , Prednisolona/análogos & derivados , Prednisolona/farmacologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION AND AIM: Autoimmune hepatitis (AIH) is an immune-mediated destruction of liver cells, in recognition of interface hepatitis, seropositivity for autoantibodies, and interface hepatitis in histology sections. Hepatocyte destruction in AIH is the direct result of CD4+ T-cell destruction. Yet, Th17 mediated immune attach and a diversity of cytokine networks, including pro-inflammatory cytokines such as Interleukin 1 (IL-1) and Interleukin 6 (IL-6), set the stage for the destructive liver damage. MATERIAL AND METHOD: Peripheral blood samples from 57 patients, with AIH, recruited from referrals to the main pediatric hospital in Tehran. Single nucleotide polymorphisms for the following cytokines genes, were evaluated through, polymerase chain reaction with sequencespecific primers (PCR-SSP) assay: IL-1a (C/T -889), IL-1α (C/T -511), IL-1ß (C/T +3962), IL-1 receptor (IL-1R; C/T Pst-I 1970), IL-1RA (C/T Mspa-I 11100), and IL-6 (C/G -174 and A/G nt565). RESULTS: Significant higher frequency of genotype AA was detected in patients in IL-6 at position nt565 (15.8% in AIH patients vs. 2.9% in controls, p = 0.003). The haplotype GA of IL-6 at -174 and nt565, was significantly overrepresented in the AIH group, compared to (20.9% of AIH vs. 1.4% in controls p < 0.0001). CONCLUSION: Results of our study, indicate significant deviation toward high yield IL-6 polymorphisms, in AIH patients. These data could bring new insights in pathophysiology of disease, which could contribute to developing novel treatments for AIH.
Assuntos
Regulação da Expressão Gênica , Hepatite Autoimune/genética , Interleucina-1/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Criança , Intervalos de Confiança , Feminino , Genótipo , Haplótipos , Hepatite Autoimune/sangue , Hospitais Pediátricos , Humanos , Irã (Geográfico) , Masculino , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Valores de ReferênciaRESUMO
OBJECTIVES: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission. METHODS: A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected. RESULTS: Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6â±â5.1 years) with a mean follow-up period of 2.9â±â3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy-nine percent achieved biochemical remission (mean time to remission 6.2â±â9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6-TGN levels ranging from 50 to 250 pmol/8â×â10 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ≤50 U/L). CONCLUSIONS: The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6-TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.
Assuntos
Azatioprina/farmacocinética , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/farmacocinética , Tioguanina/sangue , Adolescente , Azatioprina/metabolismo , Azatioprina/uso terapêutico , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Seguimentos , Hepatite Autoimune/sangue , Humanos , Imunossupressores/metabolismo , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Quimioterapia de Manutenção , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.