Analysis of null deletion polymorphism of glutathione S-transferase theta (GSTT-1), associated with anti-GSTT-1 antibodies development in transplantation.

Glutathione S-transferase theta 1 (GSTT1) is an enzyme involved in phase II biotransformation processes and a member of a multigene family of detoxifying and clearing reactive oxygen species. GSTT1 is polymorphic like other biotransforming enzymes, allowing variability in hepatic conjugation processes. Immunological recognition of the GSTT1 alloantigen, as evidenced by donor-specific antibodies formation, has previously been observed in recipients lacking GSTT1 protein (called GSTT1-, GSTT*0, null phenotype or homozygous for the GSTT1 deletion) who receive liver or kidney transplants from GSTT1+ donors and is a risk factor for the development of de novo hepatitis following liver transplants from a GSTT1 expressing donor. Antibodies against GSTT1 are demonstrated in patients who are GSTT1 null and received a transplant from a GSTT1+ donor. Understanding the local population frequency of the GSTT1 deletion is of value in understanding the potential clinical risk of developing post-transplant complications, which can be attributed to the nonexpression of GSTT1. A population of 173 healthy donors of the Murcia Region in Southeast Spain was evaluated for a null allele of GSTT1 (n = 173). DNA was extracted, and GSTT-1 null allele detection was performed by real-time polymerase chain reaction. The frequency of the null GSTT1 genotype (nonexpression or deletion of the homozygous polymorphism of the GSTT1 protein) was 17.9% (n = 31 null allele GSTT1/173 total individuals). Our data suggest that the frequency of null GSTT1 mutations in our population in Southeast Spain is 17.9%, lower than in other Caucasoid populations. This would convert our recipient population into more susceptible to nonlocal potential organ donors and less susceptible to local donors. All recipients bearing this GSTT1 deletion homozygous would be without the protein and triggering an alloantigen in the case of transplantation with a donor without deletion.

Characteristics and Factors Associated with Inflammatory Activity on Liver Biopsy in Autoimmune Hepatitis Patients Aged 50 Years or Older

Introduction: Autoimmune hepatitis is a liver inflammatory disorder characterized by portal lymphoplasmacytic hepatitis with interface activity and lobular inflammation. Objective: The objective of this study is to identify clinical features associated with advanced age and significant inflammation in liver histology. Methods: This cross-sectional analytical study evaluated the medical records of adult patients with hepatitis who received treatment in the gastroenterology and hepatology ward of a tertiary university hospital. Bivariate analysis was conducted to identify characteristics associated with an age of 50 years or older and significant histological inflammatory activity. Results: A total of 47 patients were included, with a mean age of 42.8 ± 16.0 (43.0) years. Among them, 80.9% were women, and 31.9% were 50 years or older. Liver biopsy was performed on 31 patients, and 29.0% exhibited significant inflammation. When comparing age groups, individuals aged 50 years and older had a higher median γ-glutamyl transferase (GGT; 129 vs. 282 U/L; p = 0.034) and a higher proportion of significant inflammation (50% vs. 6.7%; p = 0.024). Patients with significant inflammation on liver biopsy had a higher mean age (63.7 ± 14.0 vs. 41.0 ± 14.4; p = 0.001) and a higher proportion of patients aged 50 years or older (85.7% vs. 66.7%; p = 0.024) compared to those with mild inflammation. Conclusions: Individuals aged 50 years and older exhibited a higher median GGT and a greater proportion of significant inflammation in liver histology.

Introducción: la hepatitis autoinmune es un trastorno inflamatorio hepático caracterizado histológicamente por hepatitis linfoplasmocítica portal con actividad de interfase e inflamación lobulillar. Objetivos: identificar las características clínicas asociadas con la edad avanzada y con una inflamación significativa en la histología hepática. Métodos: estudio analítico transversal que evaluó historias clínicas de pacientes adultos con hepatitis atendidos en la sala de gastroenterología y hepatología de un hospital universitario terciario. Se realizó un análisis bivariado para identificar las características asociadas a la edad igual o mayor a 50 años y la actividad inflamatoria histológica significativa. Resultados: se incluyó a 47 pacientes con una edad media de 42,8 ± 16,0 (43,0) años. Además, el 80,9% de ellos eran mujeres y el 31,9% tenían 50 años o más. 31 pacientes fueron sometidos a biopsia hepática y el 29,0% presentó inflamación significativa. Cuando se comparó en términos de edad, los individuos de 50 años o más presentaron medianas más altas de γ-glutamiltransferasa (GGT; 129 frente a 282 U/L; p = 0,034) y una mayor proporción de inflamación significativa (50% frente a 6,7%; p = 0,024). Los pacientes con inflamación significativa en la biopsia hepática presentaron mayor edad media (63,7 ± 14,0 frente a 41,0 ± 14,4; p = 0,001) y mayor proporción de pacientes con edad igual o superior a 50 años (85,7% frente a 66,7%; p = 0,024) que las personas con inflamación leve. Conclusiones: los individuos de 50 años o más presentaron medianas más altas de GGT y mayor proporción de inflamación significativa en la histología hepática.

YouTube® in Spanish as an information source for patients with autoimmune hepatitis.

INTRODUCTION AND AIM: A large number of patients with autoimmune hepatitis (AH) seek information about their disease on the Internet. The reliability, comprehensiveness, and quality of said information in Spanish has not been studied. Our aim was to describe the characteristics of the information about AH on YouTube®. METHODS: An analytic observational study evaluated videos in Spanish about AH available on YouTube®, describing their general characteristics, viewer engagement, and information sources. Standardized tools were utilized to analyze reliability (DISCERN), comprehensiveness, and overall quality (Global Quality Score [GQS]). RESULTS: One hundred videos were included, 93% of which provided information from healthcare professionals (group 1), and 7% of which reflected patient opinions (group 2). There were differences in the median reliability (DISCERN 4 vs 2, p ≤ 0.05) and comprehensiveness (4 vs 2, p ≤ 0.05) scores between groups, but equal overall quality (GQS 3 vs 2, p = 0.2). Reliability (DISCERN 4; RIC 3-4) and comprehensiveness (4.5; IQR 3-5) were higher in videos by professional organizations, compared with those by independent users, healthcare information websites, and for-profit organizations (DISCERN 3; IQR 2.5-3.5) (p < 0.001). Reliability (DISCERN 2; IQR 1.5-3), comprehensiveness (2; IQR 1.5-2.5), and quality (GQS 2.5; IQR 1.5-3.5) were lower for videos made by for-profit organizations. CONCLUSION: The majority of videos about AH in Spanish on YouTube® have good reliability, comprehensiveness, and quality. Videos created by academic organizations had higher scores, thus their collaboration, with respect to patient opinion videos, is suggested.

CD138 immunohistochemistry identifies more plasma cells compared with hematoxylin and eosin staining in autoimmune hepatitis. An observational study.

INTRODUCTION: Autoimmune hepatitis (AIH) is associated with periportal infiltration by plasma cells. Plasma cell detection is routinely performed through hematoxylin and eosin (H&E) staining. The present study aimed to assess the utility of CD138, an immunohistochemical plasma cell marker, in the evaluation of AIH. MATERIALS AND METHODS: A retrospective study was conducted, in which cases consistent with AIH, within the time frame of 2001 and 2011, were collected. Routine H&E-stained sections were used for evaluation. CD138 immunohistochemistry (IHC) was performed to detect plasma cells. RESULTS: Sixty biopsies were included. In the H&E group, the median and interquartile range (IQR) was 6 (4-9) plasma cells/high power field (HPF) and was 10 (IQR 6-20) plasma cells/HPF in the CD138 group (p < 0.001). There was a significant correlation between the number of plasma cells determined by H&E and CD138 (p = 0.31, p = 0.01). No significant correlation was found between the number of plasma cells determined by CD138 and IgG level (p = 0.21, p = 0.09) or stage of fibrosis (p = 0.12, p = 0.35), or between IgG level and stage of fibrosis (p = 0.17, p = 0.17). No significant correlation was found between the treatment response and the number of plasma cells determined by H&E (p = 0.11, p = 0.38), CD138 (p = 0.07, p = 0.55), or stage of fibrosis (p = 0.16, p = 0.20). CD138 expression was different between the treatment response groups (p = 0.04). CONCLUSION: CD138 increased the detection of plasma cells in liver biopsies of patients with AIH, when compared with routine H&E staining. However, there was no correlation between the number of plasma cells determined by CD138 and serum IgG levels, stage of fibrosis, or response to treatment.

Biopsia hepática: experiencia en un hospital regional del sur de Chile / Liver biopsy: experience in a regional hospital in southern Chile

Introduction: Liver biopsy is an invasive procedure with a minimal rate of associated complications, which represents a highly useful strategy for the diagnosis of pathologies in the liver, when the etiology cannot be clarified by non-invasive techniques. It provides information that allows determining the progression and prognosis of liver diseases. Objectives: To evaluate the main etiology causes of liver disease in patients undergoing liver biopsy. Material and Methods: Review of the clinical record of 61 patients who underwent this procedure between 2018 and 2020 at the Hernán Henríquez Aravena hospital, demographic variables, diagnosis that motivates its performance, and associated complications. Results: Average age 58 years, of this 66% were female and 34% were male. The diagnoses that motivated this procedure were: autoimmune hepatitis, liver Tumors, and chronic liver damage of unknown etiology. 100% of the case had a satisfactory sample for the analysis and clarification of the cause of liver disease. 91% did not present complications and of the 8% associated with complications, pain was the most common. Conclusion: Liver biopsy is an effective method that allowed establishing etiology, confirming diagnosis suspicions, and evaluating the progression of liver disease with a low rate of complications.

Introducción: La biopsia hepática es un procedimiento invasivo con una tasa mínima de complicaciones asociadas, que representa una estrategia de gran utilidad para el diagnóstico de patologías a nivel del hígado, cuando a través de técnicas no invasivas no se logra esclarecer la etiología. Además, entrega información que permite determinar la progresión y pronóstico de enfermedades hepáticas. Objetivos: Evaluar las principales causas etiológicas de hepatopatías en los pacientes sometidos a biopsia hepática. Material y Método: Revisión de fichas clínicas de 61 pacientes sometidos a este procedimiento entre el año 2018 y 2020 en el hospital Hernán Henríquez Aravena, se analizaron variables demográficas, diagnóstico que motiva su realización, y complicaciones asociadas. Resultados: Edad promedio: 58 años de estos: 66% eran del sexo femenino y 34% al sexo masculino. De los diagnósticos que motivaron a la realización de la biopsia fuero: hepatitis autoinmune, tumores hepáticos y daño hepático crónico de etiología no precisada. El 100% de los casos tuvo una muestra satisfactoria para el análisis y esclarecer la causa de la hepatopatía. El 91% no presentó complicaciones y del 8% de las complicaciones presentadas, el dolor fue la principalmente descrita. Conclusiones: La biopsia hepática es un método eficaz que permitió establecer etiología, confirmar sospechas diagnósticas y evaluar progresión de enfermedades hepáticas con una baja tasa de complicación.

Hepatitis autoinmune y enfermedad celiaca en una paciente con hipertransaminasemia crónica

La hepatitis autoinmune es una patología poco frecuente en pediatría cuya incidencia ha aumentado en los últimos años. Aunque su espectro clínico es muy variado, debe sospecharse ante el aumento de transaminasas séricas tras haber descartado otras etiologías. A continuación, se presenta el caso de una paciente de 9 años con hipertransaminasemia crónica que fue diagnosticada de hepatitis autoinmune y enfermedad celiaca. (provisto por Infomedic International)

Autoimmune hepatitis is a rare pathology in pediatrics whose incidence has increased in recent years. Although its clinical spectrum is very varied, it should be suspected due to the increase in serum transaminases after having ruled out other etiologies. The case of a 9-year-old patient with chronic hypertransaminasemia who was diagnosed with autoimmune hepatitis and celiac disease is presented below. (provided by Infomedic International)

Drug-induced liver injury after covid-19 mRNA vaccine: case report

Case description: A 22-year-old female patient received the first dose of Pfizer-BioNTech vaccine (RNAm) against COVID-19; 6 days later, she presented abdominal pain located in the right hypochondrium and epigastrium, associated with emetic episodes. Re-consultation 21 days later due to the same symptoms; three days after the second dose of the vaccine was administered. Clinical findings: Pain on palpation in the right hypochondrium. Laboratories reported hepatocellular lesion and cholestasis, with negative amylase, hepatotropic virus and autoimmune hepatitis tests. Liver and biliary tract ultrasound and cholangioresonance were normal. Treatment and Results: Hyoscine and intravenous fluids as support therapy. She presented improvement in abdominal pain and progressive decrease of transaminases and bilirubin levels until normalization, and was discharged on the fifth day of hospitalization. A drug-associated hepatotoxicity (DILI) diagnosis was considered probable, in this case, secondary to vaccination against COVID-19. Clinical Relevance: The current SARS CoV-2 pandemic has spurred the development of new vaccines, the safety of which remains a concern. There is a likely causal relationship between vaccination and liver involvement in this clinical case, rather than simply a sporadic occurrence.

Descripción del caso: Paciente femenina de 22 años, quien recibió primera dosis de vacuna Pfizer-BioNTech (RNAm) contra COVID-19; presenta 6 días después, dolor abdominal localizado en hipocondrio derecho y epigastrio, asociado a episodios eméticos. Reconsulta a los 21 días por la misma sintomatología; tres días posteriores a la aplicación de la segunda dosis de la vacuna. Hallazgos clínicos: dolor a la palpación en hipocondrio derecho. Los laboratorios reportaron lesión hepatocelular y colestasis, con amilasa, estudios para virus hepatotrópos y hepatitis autoinmune negativos. La ecografía de hígado, vías biliares y colangioresonancia fueron normales. Tratamiento y Resultados: hioscina 20 mg vía oral cada 8 horas y líquidos endovenosos como terapia de soporte. Presentó mejoría del dolor abdominal y descenso progresivo de transaminasas y bilirrubinas, hasta su normalización y se dio egreso al quinto día de hospitalización. Se consideró probable diagnóstico de hepatotoxicidad asociada a medicamentos (DILI), en este caso, secundario a la vacunación contra COVID-19. Relevancia Clínica: La pandemia actual por el virus SARS CoV-2 ha impulsado el desarrollo de nuevas vacunas, cuya seguridad sigue siendo un motivo de preocupación. En este caso clínico, hay una probable relación causal entre la vacunación y el compromiso hepático, en lugar de una simple aparición esporádica.

Hepatitis autoinmune: retos y novedades / Autoimmune hepatitis: Challenges and novelties

La hepatitis autoinmune es una enfermedad crónica del hígado de etiología desconocida y que afecta generalmente a mujeres de cualquier edad. Se caracteriza por una elevación de las transaminasas y la inmunoglobulina G, autoanticuerpos e infiltrado inflamatorio portal con hepatitis de interfase en la biopsia hepática. El tratamiento generalmente se basa en la combinación de glucocorticoides y azatioprina. Sin embargo, un 20-40% de los pacientes requieren tratamientos de segunda o tercera línea por intolerancia o respuesta insuficiente. Aquí se revisarán los aspectos más importantes del diagnóstico y tratamiento de la hepatitis autoinmune con énfasis en los retos que se presentan en la práctica clínica. (AU)

Autoimmune hepatitis is a chronic inflammatory disease of the liver. The etiology is partly unknown and commonly affects women of all ages. It is characterized by increase in transaminase and immunoglobulin G levels, autoantibodies, and portal inflammatory infiltrate with interface hepatitis in the liver biopsy. The treatment is based on the combination of corticoids and azathioprine, but 20-40% of patients require second- or third-line therapies due to intolerance or insufficient response. Here, we will revise the most important aspects regarding the diagnosis and treatment of autoimmune hepatitis emphasizing the challenges faced in clinical practice. (AU)

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%.

Budesonide in the first line treatment of patients with autoimmune hepatitis / Budesonida en primera línea de tratamiento de pacientes con hepatitis autoinmune

Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug.(AU)

La budesonida es un glucocorticoide que se caracteriza por su acción local, con una baja biodisponibilidad sistémica. Desde el ensayo original publicado en 2010, en el que se comparó la budesonida con prednisona, se recomienda como una alternativa eficaz en el tratamiento de los pacientes con hepatitis autoinmune aguda o crónica no grave. En este documento, revisamos las propiedades farmacológicas generales de los glucocorticoides, la evidencia disponible para el uso de budesonida como fármaco de primera línea en estos pacientes, así como el perfil de seguridad del fármaco.(AU)

Autoimmune hepatitis: Challenges and novelties. / Hepatitis autoinmune: retos y novedades.

Autoimmune hepatitis is a chronic inflammatory disease of the liver. The etiology is partly unknown and commonly affects women of all ages. It is characterized by increase in transaminase and immunoglobulin G levels, autoantibodies, and portal inflammatory infiltrate with interface hepatitis in the liver biopsy. The treatment is based on the combination of corticoids and azathioprine, but 20-40% of patients require second- or third-line therapies due to intolerance or insufficient response. Here, we will revise the most important aspects regarding the diagnosis and treatment of autoimmune hepatitis emphasizing the challenges faced in clinical practice.

Avances en la inmunopatogenia de la hepatitis autoinmune / Advances in the immunopathogenesis of autoimmune hepatitis

RESUMEN Introducción: en la hepatitis autoinmune los mecanismos inmunopatogénicos no están totalmente esclarecidos, múltiples son las investigaciones en este campo, con vistas a enriquecer los conocimientos y ampliar las opciones terapéuticas. Objetivo: sintetizar los conocimientos más recientes acerca de la inmunopatogenia de esta enfermedad. Material y Método: se efectúa una búsqueda exhaustiva de la bibliografía disponible en SciELO, ScienceDirect, Google Académico y PubMed, incluyendo artículos de revisión, estudios experimentales, clínicos, de cohorte y metaanálisis. Desarrollo: se explican los principales mecanismos de tolerancia central y periférica, así como el papel de las subpoblaciones linfoides, las citocinas y el microambiente en la patogenia de la enfermedad. Conclusiones: los avances en el conocimiento de la inmunopatogenia de la hepatitis autoinmune permiten una mejor comprensión de esta enfermedad y son el referente para el diseño de estrategias futuras de tratamiento.

ABSTRACT Introduction: Immunopathogenic mechanisms are not fully clarified in autoimmune hepatitis; there are many investigations in this field with a view to enriching knowledge and expanding therapeutic options. Objective: To synthesize the most recent knowledge about the immunopathogenesis of this disease. Material and Methods: An exhaustive search of the bibliography available in SciELO, ScienceDirect, Google Scholar and PubMed was carried out, including review articles, experimental, clinical, cohort and meta-analysis studies. Development: The main mechanisms of central and peripheral tolerance are explained, as well as the role of lymphoid subpopulations, cytokines and the microenvironment in the pathogenesis of the disease. Conclusions: Advances in the knowledge of the immunopathogenesis of autoimmune hepatitis allow a better understanding of this disease and are the referents in the design of future treatment strategies.

Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases / Aspectos clínicos y pronósticos de pacientes con enfermedad inflamatoria intestinal asociada a enfermedades hepáticas autoinmunes

Background and aims: Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group.Methods: Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed.Results: Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006–1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1–1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815–182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215–42.43).Conclusion: Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).

Antecedentes y objetivos: Las enfermedades inflamatorias intestinales (EII) son afecciones crónicas que pueden ir acompañadas de enfermedad hepática autoinmune (EHA) o colangitis esclerosante primaria (CEP). El objetivo del estudio fue evaluar el comportamiento de pacientes con EII asociada a EHA y comparar un grupo con CEP con un grupo sin CEP.Métodos: Se evaluaron las historias clínicas de pacientes con EII asociadas con CEP, colangitis autoinmune, colangitis biliar primaria, CEP de conductos pequeños, hepatitis autoinmune (HAI) y síndromes superpuestos.Resultados: Se incluyeron 54 pacientes. De ellos, 48 (88,9%) tenían colitis ulcerosa y seis (11,1%) tenían enfermedad de Crohn; 35 (64,8%) tenían CEP y 19 (35,2%) no tenían CEP. No hubo diferencias en los resultados (tratamiento quirúrgico para la EII, trasplante de hígado o muerte) entre los grupos. El tiempo transcurrido desde el diagnóstico de EII se asoció con el tratamiento quirúrgico de la EII (p=0,041). El tiempo desde el diagnóstico de EHA (p=0,003), así como la hipertensión portal en el momento del diagnóstico (p=0,014), fueron asociado con el trasplante de hígado. Además, el diagnóstico previo de HAI se asoció con EII de novo (p=0,012).Conclusión: Ambos grupos tuvieron un comportamiento de enfermedad similar. Un mayor tiempo desde el diagnóstico de EII aumentó el riesgo de tratamiento quirúrgico (13,9%/año). Se observó un aumento del 25,9%/año en el trasplante de hígado después de diagnóstico de EIA, que se incrementó 18,22 veces por la presencia de hipertensión portal. Además, el diagnóstico de HAI se asoció con un aumento en el número de diagnósticos de EII de novo (7,1).

Budesonide in the first line treatment of patients with autoimmune hepatitis.

Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug.

Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. METHODS: Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. RESULTS: Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006-1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1-1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815-182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215-42.43). CONCLUSION: Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).

Características epidemiológicas y clínicas de pacientes con cirrosis hepática

RESUMEN Introducción: La cirrosis hepática constituye la etapa final de muchas enfermedades del hígado. Objetivo: Determinar las características epidemiológicas y clínicas de pacientes con cirrosis hepática. Métodos: Se realizó una investigación descriptiva, retrospectiva, con datos de archivo, de 57 pacientes cirróticos. Se excluyeron aquellos con datos insuficientes en la historia clínica. Las variables analizadas fueron: edad, sexo, etiología, modo de diagnóstico, comorbilidades, manifestaciones endoscópicas de la hipertensión portal, complicaciones, estadios de la enfermedad según D'Amico y clasificación de Child-Pugh. Para el análisis de los resultados se emplearon técnicas de la estadística descriptiva. Resultados: Hubo 19 pacientes (33,3 %) en el grupo de edad entre 60 y 69 años; 31 (54,4 %) mujeres y 26 (45,6 %) hombres. El virus de la hepatitis C fue encontrado en 21 pacientes (36,8 %). El 96,4 % de los enfermos se diagnosticaron mediante ecografía abdominal; 12 (21,1 %) presentaron ascitis y 38 (66,6 %) manifestaciones endoscópicas de hipertensión portal. En estadio 4 de D'Amico estaban 20 (35 %) enfermos y 26 (45,6 %) en estadio de Child-Pugh A; 24 (42,1 %) en Child-Pugh B y 7 (12,3 %) en Child-Pugh C. Conclusiones: La cirrosis hepática predomina en la séptima década de la vida, en el sexo femenino. Prevalece el ultrasonido abdominal como modo de diagnóstico. Las causas más frecuentes son el virus de hepatitis C y el alcoholismo. La ascitis es la complicación que más se presenta. La mayoría de los pacientes muestran signos de hipertensión portal. Predominan las formas no compensadas de la enfermedad.

ABSTRACT Introduction: Liver cirrhosis is the end stage of many liver diseases. Objective: To determine the epidemiological and clinical characteristics of patients with liver cirrhosis. Results: There were 19 patients (33.3%) in the age group between 60 and 69 years; 31 (54,4 %) women and 26 (45,6 %) men. Hepatitis C virus was found in 21 patients (36,8 %). 96,4 % of the patients were diagnosed by abdominal ultrasound; 12 (21,1 %) presented ascites and 38 (66,6 %) endoscopic manifestations of portal hypertension. In D'Amico stage 4 there were 20 (35 %) patients and 26 (45,6 %) in Child-Pugh A stage; 24 (42,1 %) in Child-Pugh B and 7 (12,3 %) in Child-Pugh C. Conclusions: Liver cirrhosis predominates in the seventh decade of life, in females. Abdominal ultrasound prevails as a diagnostic mode. The most common causes are hepatitis C virus and alcoholism. Ascites is the most common complication. Most patients present with signs of portal hypertension. Uncompensated forms of the disease predominate.

Corticoterapia con intención de rescate en pacientes con hepatitis autoinmune severa: ¿el trasplante hepático es evitable?

Resumen: Introducción: La hepatitis autoinmune es una enfermedad cuya presentación clínica inicial puede manifestarse de diversas formas, siendo su presentación aguda con aumento de los niveles de bilirrubina, caída de la función biosintética y necrosis masiva/submasiva o cirrosis en la histología, marcadores de severidad de la misma. La decisión de iniciar tratamiento con corticoides en este escenario resulta un desafío en la práctica clínica. Los objetivos del presente trabajo fueron evaluar el grado de respuesta al tratamiento, los predictores de respuesta, y la supervivencia global y libre de trasplante en pacientes cuyo debut clínico fue de forma aguda y severa. Resultados: Fueron incluidos 33 pacientes con bilirrubina total mayor a 2.5 mg/dl, sin tratamiento previo (naive), que cumplían criterios diagnósticos según el grupo internacional de hepatitis autoinmune. El 97% eran mujeres con una mediana de edad de 52 años, el 58% se encontraba en etapa de cirrosis con un MELD promedio de 24, y el 15% presentaba una necrosis masiva/submasiva en la muestra de biopsia hepática. En 27 casos se inició corticoterapia. El 66.7 % evolucionó con remisión completa, 14.8 % con remisión parcial, y en 18.5% hubo falla al tratamiento corticoideo. La colesterolemia basal y la presencia de encefalopatía hepática fueron predictores de no respuesta al tratamiento corticoideo, mientras que el MELD pre-tratamiento y la colesterolemia basal fueron las variables estadísticamente significativas asociadas a falla en el rescate del trasplante hepático. En los pacientes tratados con corticoides, la supervivencia global y libre de trasplante a 5 años en función del MELD (<25 vs ≥ 25) fue del 90% vs 60% respectivamente. Conclusión: Las altas tasas supervivencia logradas bajo tratamiento médico que fueron evidenciadas en esta serie reafirman la necesidad de priorizar el uso de corticoides en pacientes con hepatitis autoinmune aguda y severa.

Abstract: Introduction: Autoimmune hepatitis can initially manifest itself in various clinical ways. Its acute presentation with increased levels of bilirubin, fall of biosynthetic function and massive/submassive necrosis or cirrhosis in histology, is a marker of severity of it. The decision to start corticosteroid treatment in this scenario is a challenge in clinical practice. The objectives of this work were to assess the degree of response to treatment, response predictors, and overall and transplant-free survival in patients whose clinical debut was acute and severe. Results: 33 patients with total bilirubin greater than 2.5 mg/dL, without prior (naive) treatment, who met diagnostic criteria according to the international autoimmune hepatitis group, were included. 97% were women with a median age of 52, 58% were in the cirrhosis stage with an average MELD of 24, and 15% had massive/submassive necrosis in the liver biopsy sample. In 27 cases treatment with cortiocosteroids was initiated, 66.7% evolved with complete remission, 14.8% with partial remission, and in 18.5% there was failure of corticosteroid treatment. Basal cholesterol and the presence of hepatic encephalopathy were predictors of non-response to corticosteroid treatment, while pre-treatment MELD and basal cholesterol were the statistically significant variables associated with liver transplant rescue failure. In patients treated with corticosteroids, overall and transplant-free survival at 5 years based on MELD (<25 vs ≥ 25) was 90% vs 60% respectively. Conclusion: The high survival rates achieved under medical treatment that were demonstrated in this series reaffirm the need to prioritize the use of corticosteroids in patients with acute and severe autoimmune hepatitis.

Resumo: Introdução: A hepatite autoimune é uma doença cuja apresentação clínica inicial pode se manifestar de várias formas, sendo sua apresentação aguda com níveis elevados de bilirrubina, descida na função biossintética e necrose maciça/submassiva ou cirrose em histologia, marcadores de gravidade dela. A decisão de iniciar o tratamento corticosteroide nesse cenário é um desafio na prática clínica. Os objetivos deste trabalho foram avaliar o grau de resposta ao tratamento, preditores de resposta e sobrevida geral e livre de transplantes em pacientes cuja estréia clínica foi aguda e grave. Resultados: Foram incluídos 33 pacientes com bilirrubina total superior a 2,5 mg/dL, sem tratamento prévio (ingênuo), que atendiam aos critérios diagnósticos segundo o grupo internacional de hepatite autoimune. 97% eram mulheres com idade mediana de 52 anos, 58% estavam em estágio de cirrose com um MELD médio de 24, e 15% tinham necrose maciça/submassiva na amostra de biópsia hepática. Em 27 casos foi iniciado o tratamento médico e, em 6 casos, o transplante de fígado foi alcançado sem terapia prévia. 66,7% evoluíram com remissão completa, 14,8% com remissão parcial e, em 18,5%, houve falha no tratamento corticosteroide. O colesterol basal e a presença de encefalopatia hepática foram preditores de não resposta ao tratamento corticosteroide, enquanto o meld pré-tratamento e o colesterol basal foram as variáveis estatisticamente significativas associadas à falha de resgate do transplante de fígado. Em pacientes tratados com corticosteroides, a sobrevida geral e livre de transplante aos 5 anos com base no MELD (<25 vs ≥ 25) foi de 90% vs 60%, respectivamente. Conclusão: As altas taxas de sobrevivência alcançadas sob tratamento médico demonstrado nesta série reafirmam a necessidade de priorizar o uso de corticosteroides em pacientes com hepatite autoimune aguda e grave.

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.

Síndrome de superposición de hepatitis autoinmune y colangitis biliar primaria asociada a trombosis de vena porta post COVID-19

Presentamos el caso de una mujer de 53 años con antecedentes de artritis reumatoide que, tras recuperarse de un cuadro de COVID-19grave, desarrolló hemorragia digestiva como manifestación de hipertensión portal e insuficiencia hepática progresiva. Basados en la serología y ecografía, se diagnosticó un síndrome overlap de hepatitis autoinmune y colangitis biliar primaria asociado a trombosis de vena porta. La respuesta a la corticoterapia y anticoagulación fue favorable. El compromiso hepático, inducido por el virus, está descrito en la COVID-19. Sin embargo, pueden desarrollarse enfermedades autoinmunes y fenómenos tromboembólicos, teniendo el hígado como órgano diana.