RESUMO
PURPOSE: There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. MATERIAL AND METHODS: Over 3 years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3 months before imaging, and a standardized histopathological score for fibrosis (F0-F4) and inflammatory activity (PPA0-4) was used as a reference. Statistical analysis included independent t test, Mann-Whitney U-test, and ROC (receiver operating characteristic) analysis. RESULTS: T1 mapping values were significantly higher in patients with advanced fibrosis (F0-2 vs. F3-4; p < 0.015), significant fibrosis (F0-1 vs. F2-4; p < 0.005), and significant inflammatory activity (PPA 0-1 vs. PPA 2-4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). CONCLUSION: A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals.
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: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.
Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.
RESUMO
The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine (AZA). Budesonide has shown promise in inducing a complete biochemical response (CBR) with fewer adverse effects and is considered an optional first-line treatment, particularly for patients without cirrhosis; however, it is worth noting that the design of that study favored budesonide. A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered. Current guidelines recommend mycophenolate mofetil (MMF) for patients who are intolerant to AZA. It is important to mention that the evidence supporting this recommendation is weak, primarily consisting of case series. Nevertheless, MMF has demonstrated superiority to AZA in the context of renal transplant. Recent comparative studies have shown higher CBR rates, lower therapeutic failure rates, and reduced intolerance in the MMF group. These findings may influence future guidelines, potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis. Until recently, the only alternative to corticosteroids was lifelong maintenance treatment with AZA, which comes with notable risks, such as skin cancer and lymphoma. Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies, whether relying on histological criteria, strict biochemical criteria, or a combination of both. Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo. However, these interesting findings have yet to be replicated by other research groups. Additionally, second-line drugs, such as tacrolimus, rituximab, and infliximab, should be subjected to controlled trials for further evaluation.
RESUMO
Resumen La hepatitis autoinmune (HAI) es una inflamación hepatocelular progresiva. En la Unidad de Hepatología y Alcoholismo del hospital se atienden aproximadamente 550 pacientes anualmente, muchos de ellos con diagnóstico de HAI. El objetivo de este trabajo fue evaluar las características clínicas, epidemiológicas y los parámetros de laboratorio de pacientes con HAI desde 2012 hasta 2018. Se incluyeron 44 pacientes: 40 con HAI tipo I y 4 seronegativos. El 91% fueron mujeres con edades entre 13 y 68 años; la forma de presentación más frecuente fue la hepatitis aguda. Se realizó biopsia en 32 pacientes; 50% mostraban características de HAI (hepatitis de interfase) y 35% presentaban cirrosis en la histología. El estudio ofrece una imagen aproximada de las particularidades de la HAI de la población atendida en este hospital. Respecto a otras poblaciones, esta comunicación muestra un mayor porcentaje de pacientes de sexo femenino, con alta preponderancia de presentación aguda y de las enfermedades autoinmunes asociadas.
Abstract Autoimmune hepatitis (AIH) is a progressive hepatocellular inflammation. Approximately 550 patients are treated per year in the Hepatology and Alcoholism Unit of the hospital, many of them with a diagnosis of AIH. The objective was to evaluate clinical and epidemiological characteristics and laboratory parameters of patients with AIH from 2012 to 2018; 44 patients were included, 40 with type I AIH and four seronegative patients. Ninety- one per cent were women aged between 13 and 68 years old. The most frequent form of presentation (54.5%) was acute hepatitis. Thirty-two patients required biopsy; 50% showed features of AIH (interphase hepatitis) and 35% had histologic cirrhosis. The study offers an approximate image of the particularities of AIH in the population treated in this hospital. Compared to other populations, this communication shows a higher percentage of female patients, with a high preponderance of acute presentation and associated autoimmune diseases.
Resumo A hepatite autoimune (HAI) é uma inflamação hepatocelular progressiva. Na Unidade de Hepatologia e Alcoolismo do hospital, aproximadamente 550 pacientes são atendidos por ano, muitos deles com diagnóstico de HAI. O objetivo deste trabalho foi avaliar as características clínicas, epidemiológicas e parâmetros laboratoriais de pacientes com HAI de 2012 a 2018. Foram incluídos 44 pacientes, 40 com HAI tipo I e quatro soronegativos. Noventa e um por cento foram mulheres com idades entre 13 e 68 anos; a forma de apresentação mais comum foi a hepatite aguda. Biópsias foram realizadas em 32 pacientes, 50% apresentando características de HAI (hepatite de interface) e 35% com cirrose na histologia. O estudo fornece uma visão aproximada das características da HAI na população atendida neste hospital. Em comparação com outras populações, esta comunicação mostra uma maior proporção de pacientes do sexo feminino, com alta incidência de apresentação aguda e das doenças autoimunes associadas.
RESUMO
Introducción: La respuesta al tratamiento inmunosupresor en la hepatitis autoinmune influye en el curso clínico de la enfermedad y se asocia a mayor sobrevida. Objetivo: Describir la respuesta al tratamiento inmunosupresor en pacientes con hepatitis autoinmune. Método: Se realizó un estudio descriptivo, longitudinal, ambispectivo, en 32 enfermos con hepatitis autoinmune, los cuales recibieron tratamiento inmunosupresor con evaluación de la respuesta a los 6 meses. Las variables incluidas fueron: tipo de hepatitis autoinmune, forma de presentación, forma de debut y respuesta al tratamiento. Se utilizaron medidas descriptivas de resumen: media y desviación estándar para variables cuantitativas y porcentaje para las variables cualitativas. Para estimar la función de supervivencia se utilizó la curva de Kaplan-Meier y Log-rank para la comparación de medias. Resultados: El 71,9 % de los enfermos estaban con cirrosis en el momento del diagnóstico. Los 13 pacientes con remisión bioquímica permanecieron sin progresión en la evaluación actual. La supervivencia en los pacientes respondedores fue del 100 % y en los no respondedores de 47,5 % a los 10 años de seguimiento. Conclusiones: La respuesta al tratamiento inmunosupresor tiene un impacto positivo en la no progresión de la hepatitis autoinmune y se asoció a mayor supervivencia.
Introduction: The response to immunosuppressive treatment in autoimmune hepatitis influences the clinical course of the disease and is associated with a longer survival. Objective: Describe the response to immunosuppressive treatment in patients with autoimmune hepatitis. Method: A descriptive, longitudinal, ambispective study was carried out in 32 patients with autoimmune hepatitis, who received immunosuppressive treatment with response evaluation at 6 months. The variables included were: type of autoimmune hepatitis, form of presentation, form of onset, and response to treatment. Descriptive summary measures were used: mean and standard deviation for quantitative variables and percentage for qualitative variables. To estimate the survival function, the Kaplan-Meier curve and Log-rank were used to compare means. Results: 71.9 % of the patients were already cirrhotic at the time of diagnosis. The 13 patients with biochemical remission, remained without progression in the current evaluation. Survival in responding patients was 100 %, while in non-responders it was 47.5% at 10-year follow-up. Conclusions: The response to immunosuppressive treatment has a positive impact on the non-progression of autoimmune hepatitis and was associated with greater survival.
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: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. PATIENTS AND METHODS: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. RESULTS: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). CONCLUSIONS: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Recidiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas contra COVID-19/efeitos adversos , Estudos Retrospectivos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Estudos Prospectivos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , SARS-CoV-2 , Idoso , Adulto , Imunização Secundária , Fatores de Risco , Transplante de Fígado , Imunossupressores/efeitos adversosRESUMO
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
BACKGROUND AND PURPOSE: Liver injury after Covid-19 vaccine has been described, although the incidence was not well established. We aimed to compare cumulative incidence of new onset liver test alteration after Covid-19 vaccination, and to compare with an historical control of influenza vaccination. METHODS: We conducted a retrospective cohort study which included adults who received at least one dose of Covid-19 vaccine from January 1 to May 30, 2021 and a control group who received a single dose of influenza vaccine during 2019, in a tertiary medical center from Argentina. RESULTS: We included 29 798 patients in Covid-19 vaccine group and 24 605 in influenza vaccine group. Liver function tests were performed in 7833 (26.9%) in Covid-19 vaccine group and 8459 (34.37%) in influenza vaccine group. Cumulative incidence at 90 days of new onset liver enzyme test alteration was 4.7 per 1000 (95% 4.0-5.5) for Covid-19 group, and 5.1 per 1000 (95% 4.3-6.1) for the influenza vaccine group (p value = 0.489). Two patients in the Covid-19 vaccine group developed immune mediated liver injury. CONCLUSIONS: We found no difference in liver test alteration between groups. These findings support the safety of Covid-19 vaccines. While we have identified two cases that are consistent with immune mediated liver injury following COVID-19 vaccination, we believe that the available data is insufficient to attribute them solely to the vaccination.