[Seronegative autoimmune hepatitis]. / Hepatitis autoinmune seronegativa.

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.

Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis.

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.

Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis?

OBJECTIVE: Autoimmune hepatitis is a rare inflammatory disease of the liver that is characterized by elevated liver enzymes. The hemoglobin, albumin, lymphocyte, and platelet score, which is derived from hemoglobin, serum albumin, circulating lymphocyte count, and platelet count, is also associated with inflammatory conditions. The aim was to examine the hemoglobin, albumin, lymphocyte, and platelet score of patients with autoimmune hepatitis and to compare it to that of healthy individuals in this retrospective analysis. METHODS: Subjects diagnosed with autoimmune hepatitis were enrolled in the study, and healthy individuals were enrolled as controls. Moreover, autoimmune hepatitis subjects were grouped into mild or moderate/advanced fibrosis. Furthermore, aspartate to platelet ratio index, Fibrosis-4, and hemoglobin, albumin, lymphocyte, and platelet scores of the autoimmune hepatitis patients and controls were compared. In addition, the hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients with mild fibrosis is compared to that of those with moderate/advanced fibrosis. RESULTS: The mean hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients was 44.2±14.5 while this value was 76.8±15.5 in control subjects. The hemoglobin, albumin, lymphocyte, and platelet score was significantly reduced in autoimmune hepatitis patients than healthy controls (p<0.001). The hemoglobin, albumin, lymphocyte, and platelet score was significantly and negatively correlated with C-reactive protein, aspartate, alanine transaminase, gamma glutamyl transferase, aspartate to platelet ratio index, and Fibrosis-4 values. A hemoglobin, albumin, lymphocyte, and platelet score that was lower than 52.3 had 83% sensitivity and 73% specificity in predicting autoimmune hepatitis. The sensitivity and specificity of the hemoglobin, albumin, lymphocyte, and platelet score were higher than the Fibrosis-4 score in predicting moderate/advanced fibrosis in autoimmune hepatitis. CONCLUSION: We suggest that the hemoglobin, albumin, lymphocyte, and platelet score be used as an additional noninvasive diagnostic tool for autoimmune hepatitis and to predict moderate/advanced liver fibrosis in patients with autoimmune hepatitis.

Anti-ribosomal P (anti-P) antibodies in patients with autoimmune hepatitis.

OBJECTIVE: Anti-P-ribosomal antibody is a biomarker of systemic lupus erythematosus mainly associated with renal, nervous, and hepatic involvement. Systemic lupus erythematosus may present with features similar to autoimmune hepatitis. This study aimed to investigate the association of Anti-P-ribosomal antibodies in systemic lupus erythematosus compared to autoimmune hepatitis in the general Brazilian population. Autoimmune hepatitis and systemic lupus erythematosus share several clinical features. ÛªAnti-P ribosomal antibody is a biomarker for systemic lupus erythematosus. The association between anti-P ribosomal antibody and autoimmune hepatitis has shown conflicting results. Our results showed no association between anti-P ribosomal antibody and autoimmune hepatitis. Published studies have shown associations between anti-ribosomal P (anti-P) antibody and systemic lupus erythematosus with hepatic manifestations. This has been reported also in autoimmune hepatitis. However, the consistency of the latter association remains controversial. This study aimed to evaluate the frequency of anti-P antibodies in autoimmune hepatitis using two different immunoassays. METHODS: One-hundred and seventy-seven patients with autoimmune hepatitis were screened, and 142 were analyzed for anti-P antibody positivity. The samples were first analyzed using two different immunoassays: enzyme-linked immunosorbent assay (ELISA) and chemiluminescence and then compared with a group of 60 patients with systemic lupus erythematous. The positive samples were subjected to western blot analysis. RESULTS: Anti-P was found in 5/142 autoimmune hepatitis cases (3.5%) by chemiluminescence and in none by ELISA. Among the five chemiluminescence-positive autoimmune hepatitis samples, on anti-P western blot analysis one was negative, two were weakly positive, and two were positive. In contrast, anti-P was detected in 10/60 patients with systemic lupus erythematosus (16.7%) and presented higher chemiluminescence units than the autoimmune hepatitis samples. CONCLUSION: A low frequency of anti-P antibodies was observed in autoimmune hepatitis, suggesting that this test is not useful for the diagnosis or management of this disease.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Evaluación del panel de enfermedades hepáticas autoinmunes (INMUNOBLOT) en el diagnóstico de enfermedades hepáticas / Utility of the detection of autoantibodies in autoinmune liver diseases using immunoblot

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.

[Utility of the detection of autoantibodies in autoinmune liver diseases using immunoblot]. / Evaluación del panel de enfermedades hepáticas autoinmunes (INMUNOBLOT) en el diagnóstico de enfermedades hepáticas.

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.

Autoimmune Hepatitis with Acute Presentation: Clinical, Biochemical, and Histological Features of 126 Patients.

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors. Methods: A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used. Results: A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.

Hepatitis autoinmune en pediatría, una revisión del Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPGHAN) / Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with nonspecific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. / Hepatitis autoinmune en pediatría, una revisión del Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPGHAN).

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with non-specific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

Autoimmune hepatitis presenting with peripheral eosinophilia: Case report and literature review.

Acute hepatitis presenting with blood eosinophilia are scarcely reported. Different clinical courses of autoimmune hepatitis (AIH) have been associated with acute hepatitis with eosinophilia, however it is still unclear if the latter is a common manifestation of different autoimmune diseases, part of a similar spectrum of eosinophil-associated liver injury or even a trigger to AIH. We report a case of a 32 years old woman who presented with subacute hepatitis, peripheral eosinophilia, hypergammaglobulinemia and liver biopsy suggestive of AIH. The role of eosinophils in autoimmune liver diseases deserves further studies in order to clarify its physiopathology aspects.

Prevalence and Clinical Significance of Autoantibodies in Children with Overweight and Obesity with Nonalcoholic Fatty Liver Disease.

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.

Hepatopatías autoinmunes. Hallazgos clínicos y de laboratorio en pacientes de un hospital de referencia nacional / Autoimmune liver diseases. Clinical and laboratory findings in patients in a national reference hospital

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.

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.

EVALUATION OF PATIENTS WITH AUTOIMMUNE HEPATITIS IN A SPECIALIZED OUTPATIENT CLINIC IN SOUTHERN BRAZIL.

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.

Autoimmune sequential overlap syndrome (autoimmune hepatitis/primary sclerosing cholangitis) and inflammatory bowel disease: three clinical cases.

Inflammatory bowel disease (IBD) is related to different liver extraintestinal manifestations and occurs with or without a link to disease activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation. Other autoimmune hepatopathies may develop during the evolution of the latter, which is known as overlap syndrome. Sequential overlap syndrome occurs when these conditions appear in subsequent stages, and it is less frequently associated with IBD. We report three cases of sequential overlap syndrome with autoimmune hepatitis as the first manifestation, followed by PSC after 7-19 years and subsequently IBD. Liver extraintestinal manifestations may precede IBD by several years. Therefore, it is crucial to keep this association in mind, thereby reducing the diagnostic delay.

Clinical and laboratory data in pediatric autoimmune hepatitis: study from referral center in Iran.

BACKGROUND: Autoimmune hepatitis (AIH) is an auto-inflammatory liver disease of children and adults, affecting patients of any age, sex, race or ethnicity, with more prevalence in females. OBJECTIVE: The aim of this study was to evaluate clinical manifestation, laboratory findings, and outcome of children with autoimmune hepatitis. MATERIALS AND METHODS: We evaluated 86 patients treated and followed with final diagnosis of AIH between years 2010 to 2018. Physical findings (including jaundice, hepatomegaly, splenomegaly and encephalopathy), liver enzymes, liver histology and autoantibodies (including ANA, Anti LKM-1 and ASMA) were extracted from medical files. Then the patients were followed for their final outcome (including response to medical treatment or successful treatment withdrawal, liver transplantation or death). RESULTS: Among 86 patients with AIH with mean age 9.10±4.36 years old, 66.27% were females. Jaundice (75.6%) and hepatomegaly (46.5%) were the most frequent physical findings, followed by splenomegaly (32.6%) and encephalopathy (17.4%). Aminotransferases including AST and ALT were elevated at least 3 times more than upper limit of normal in most of the patients (61.6% and 55.81%, respectively). Autoantibodies were available in 53 of 86 patients, 24.5% had AIH-1, 3.8% had AIH-II and 67.9% were seronegative. Medical treatment including prednisolone and azathioprine was started for patients, 53 of 86 cases (61.6%) had remission and 11 of 86 (13.7%) tolerated medication withdrawal successfully. Among all cases, 26 (30.2%) patients needed liver transplantation. Mortality rate was 9 among 86 cases (10.5%). CONCLUSION: Jaundice and hepatomegaly was the most frequent clinical findings. Mortality rate was 10.5.