Marcadores humorales y estudio ultrasonográfico en pacientes diabéticos con enfermedad hepática por acumulación de grasa / Humoral markers and ultrasonographic study in diabetic patients with liver disease due to fat accumulation

Introducción: La enfermedad hepática grasa no alcohólica se caracteriza por: una acumulación de grasa en el hígado en forma de triacilglicéridos, ausencia de inflamación, fibrosis y un consumo de menos de 30 grados de alcohol al día. Esta afección se asocia a la diabetes mellitus (sobre todo tipo 2), y se observa un creciente aumento en el número de consultas hospitalarias por esta causa. Objetivo: Determinar la relación de los marcadores humorales y el estudio ultrasonográfico en pacientes diabéticos con enfermedad hepática grasa no alcohólica. Métodos: Se realizó una investigación descriptiva y transversal en la Consulta Provincial de Hepatología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro», en el período de marzo 2019 a diciembre 2020. El universo de estudio estuvo conformado por 89 pacientes (con edades mayores o iguales a 19 años, de ambos sexos); la muestra estuvo constituida por 66 pacientes que fueron seleccionados por muestreo no probabilístico. Resultados: Predominaron los pacientes con edades entre 40 y 59 años, masculinos, de piel blanca, y procedencia urbana. El grado de esteatosis predominante fue el grado 1 (leve). Los marcadores humorales (glicemia, gamma glutamil transpeptidasa, albúmina e índice de Ritis) fueron los más afectados patológicamente. Conclusiones: Los estudios ultrasonográficos mostraron una asociación estadísticamente significativa con alteración de los marcadores humorales de lesión hepática, lo cual puede alertar de una posible evolución desfavorable de esta enfermedad.

Introduction: non-alcoholic fatty liver disease is characterized by an accumulation of fat in the liver in the form of triacylglycerides, absence of inflammation, fibrosis and a consumption of less than 30 degrees of alcohol per day. This condition is associated with diabetes mellitus (especially type 2), and there is a growing increase in the number of hospital visits for this cause. Objective: to determine the relationship between humoral markers and ultrasonographic study in diabetic patients with non-alcoholic fatty liver disease. Methods: a descriptive and cross-sectional investigation was carried out in the provincial hepatology consultation at "Arnaldo Milián Castro" Clinical and Surgical University Hospital from March 2019 to December 2020. The study universe consisted of 89 patients (older than or equal to 19 years, of both genders); the sample consisted of 66 patients who were selected by non-probabilistic sampling. Results: white male patients aged between 40 and 59 years living in urban areas predominated. The predominant degree of steatosis was grade 1 (mild). Humoral markers (glycemia, gamma- glutamyl transpeptidase, albumin and De Ritis ratio) were the most pathologically affected. Conclusions: ultrasonographic studies showed a statistically significant association with changes in humoral markers of liver injury, which may alert to a possible unfavorable evolution of this disease.

Hiperferritinemia y sospecha de sobrecarga de hierro en pacientes del Hospital Pablo Tobón Uribe, entre los años 2010 a 2020 / Hyperferritinemia and suspected iron overload in patients at the Pablo Tobón Uribe Hospital, between 2010 and 2020

Introducción. El objetivo de esta investigación fue comparar el perfil bioquímico y clínico de los pacientes con hiperferritinemia secundaria a hemocromatosis hereditaria (HH), frente a aquellos con hiperferritinemia por causas sospechosas de sobrecarga de hierro (Fe) diferentes a la HH. Metodología. Se estudiaron 92 pacientes (61 hombres y 31 mujeres), remitidos tras la detección de valores de ferritina >300 µg/L en hombres y >200 µg/L en mujeres. En todos se analizaron datos demográficos generales, comorbilidades, motivo de remisión para estudios de hiperferritinemia, manifestaciones clínicas, antecedente familiar de HH y tratamiento reci-bido. Los resultados de las pruebas de laboratorio, imagenología, hallazgos histopatológicos y estudios genéticos, se describieron según la disponibilidad. Resultados. El 96,74 % de los pacientes fueron evaluados en consulta externa, 86,96 % procedían de Medellín o de otros municipios de Antioquia, Colombia. La edad promedio de los participantes fue de 52 años, la principal razón para ser derivados para estudios fue la elevación de los marcadores de Fe sérico, la causa más frecuente de hiperferritinemia fueron los diagnósticos diferentes a la HH (64,13 %) y entre quienes no tenían HH, la etiología metabólica fue la más común (59,32 %). Los pacientes con HH tuvieron niveles más elevados de ferritina y Fe sérico, mientras que en el grupo sin HH se presentaron mayores elevaciones en la saturación de transferrina, transfe-rrina y transaminasas. En pacientes con sobrecarga de Fe, la mutación más frecuentemente encontrada fue la homocigota H63D (36,67 %). Finalmente, 93,94 % de los pacientes con HH recibieron tratamiento con flebotomías, mientras que los cambios en el estilo de vida fueron indicados en el 55,93 % de los pacientes sin HH. Conclusiones. La hiperferritinemia es una presentación clínica frecuente y es importante hacer un abordaje sistemático para identificar sus causas. Aunque la HH es una causa importante de elevación persistente de ferritina, en el enfoque de los pacientes con esta condición, se deben descartar etiologías más frecuentes como la hiperferritinemia de etiología metabólica.

Introduction. The aim of this investigation was to compare the biochemical and clinical profile of patients with secondary hyperferritinemia caused by hereditary hemochromatosis (HH), versus those with hyperferritinemia due to suspected causes of iron (Fe) overload other than HH. Methodology. A total of 92 patients (61 men and 31 women) referred after the detection of ferritin values >300 µg/L in men and >200 µg/L in women were studied. General demographic data, comorbidities, referral reasons for hyperferritinemia studies, clinical manifestations, family history of HH, and treatment received were analyzed in all patients. The results of laboratory tests, medical imaging, histopatho-logical findings, and genetic studies were described based on availability. Results. Of all patients, 96.74% were evaluated as outpatients, 86,96% from the municipality of Medellin in Antioquia, Colombia. The average age of the participants was 52 years, the main reason for being referred for studies was the elevation of serum Fe markers, the most frequent cause of hyperferritinemia in the population studied were conditions other than HH (64.13%), and among those who did not have HH, the metabolic etiology was the most common cause (60%). Patients with HH had higher levels of ferritin and serum Fe, while in the group without HH there were greater elevations of transferrin saturation, transferrin and transaminases. In patients with iron overload, the most frequently found mutation was the homozygous H63D (36.67%). Finally, 93.94% of the patients with HH received phlebotomy treatment, while changes in lifestyle were indicated in 55.93% of patients without HH. Conclusions. Hyperferritinemia is a frequent clinical presentation and it is important to make a systematic approach to identify its causes. Although HH is an important cause of persistent ferritin elevation, in the approach to patients with this condition, more frequent etiologies such as hyperfe-rritinemia of metabolic etiology should be ruled out.

Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

Hipertransaminasemia en coledocolitiasis / Hypertransaminasemia in choledocholithiasis

Introducción. La coledocolitiasis aguda se presenta cuando un cálculo se impacta en el conducto biliar distal. Usualmente se manifiesta con un patrón colestásico, con aumento de la AST y ALT leve o moderado. Sin embargo, se han reportado series de casos de coledocolitiasis con AST y ALT con valores >400 UI/L, lo que puede llevar al médico a considerar una hepatitis como diagnóstico presuntivo, en vez de una coledocolitiasis. Con esta revisión exploratoria se pretende explicar esta forma de presentación, y sugerir los pasos que debe dar el clínico para identificar estos casos y brindar un diagnóstico oportuno y certero. Metodología. Se realizó una revisión exploratoria utilizando los buscadores PubMed, BIREME (BVS), LILACS y Google Académico, con las palabras MeSH "choledocholithiasis", "transaminases" y el conector "and", así como los términos DeCS "coledocolitiasis", "transaminasas" y el conector "y". Resultados. Se incluyeron en el análisis un total de 20 estudios relacionados con el tema coledocolitiasis y elevación de AST o ALT >400 UI/L. Se encontró que el aumento de AST o ALT entre 400 UI/L y 500 UI/L se presentó en el 5,76% de los casos, valores entre 500 UI/L y 800 UI/L en el 36,8%, entre 800 UI/L y 1.000 UI/L en el 9%, y valores >1.000 UI/L en el 6,43% de los casos. Conclusión. La coledocolitiasis con elevación de transaminasas AST o ALT >400 UI/L es una situación que debe tenerse presente, en particular en personas jóvenes, y en aquellos sin historia de problemas hepáticos previos. Es necesario que el médico tenga el diagnóstico presuntivo de coledocolitiasis, aun con niveles de transaminasas que puedan sugerir una hepatitis, y analizar las diferentes variables que son indispensables para lograr un diagnóstico preciso.

Introduction. Acute choledocholithiasis occurs when a stone impacts the distal bile duct. It usually manifests with a cholestatic pattern, with a mild or moderate increase in ASL and ALT. However, series of cases of choledocholithiasis have been reported with AST and ALT values >400 IU/L, which may lead the physician to consider hepatitis as a presumptive diagnosis, instead of choledocholithiasis. This scoping review is intended to explain this form of presentation, and to suggestthe steps that the clinician should take to identify these cases and provide a timely and accurate diagnosis. Methodology. A scoping review was carried out using PubMed, BIREME (BVS), LILACS and Google Scholar search engines, with the MeSH words "choledocholithiasis", "transaminases" and the "and" connector, as well as the DeCS terms "coledocolitiasis", "transaminasas" and the "y" connector. Results. A total of 20 studies related to the topic of choledocholithiasis and elevation of AST or ALT >400 IU/L were included in the analysis. It was found that the increase in AST or ALT between 400 IU/L and 500 IU/L occurred in 5.76% of the cases, values between 500 IU/L and 800 IU/L in 36.8%, between 800 IU/L and 1,000 IU/L in 9%, and values >1,000 IU/L in 6.43% of the cases. Conclusion. Choledocholithiasis with elevated AST or ALT transaminases >400 IU/L is an occurrence that should be taken into account, particularly in young people, and in those without a history of previous liver problems. It is necessary for the specialist to have a presumptive diagnosis of choledocholithiasis, even with transaminase levels that may suggest hepatitis, and to analyze the different variables that are essential to achieve an accurate diagnosis.

Cambios en la función hepática causados por COVID-19 y su impacto en el resultado clínico del paciente: una revisión sistemática / Changes in liver function tests caused by COVID-19 and impact on patient outcome: a systematic review

Resumen Introducción: En marzo de 2020, la Organización Mundial de la Salud (OMS) decretó la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), que consiste en la infección por coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2). Este virus utiliza la enzima convertidora de angiotensina II (ECA-II) como receptor celular humano, que está presente en el tejido pulmonar, cardíaco, gastrointestinal, hepático, renal y vascular, lo que configura un potencial de afectación multisistémica por parte del patógeno. El hígado puede resultar dañado tanto por la liberación excesiva de citocinas inflamatorias en COVID-19 como por la adopción de fármacos con potencial hepatotóxico en el tratamiento de sus síntomas. Objetivo: analizar la relación entre los cambios en la función hepática causados por el SARS-CoV-2 y su impacto en el pronóstico del paciente. Métodos: el presente estudio consiste en una revisión sistemática, realizada a partir de estudios seleccionados de las bases de datos PMC, LILACS y SciELO. Después de aplicar los criterios de inclusión y exclusión, se definieron 30 artículos para componer la base de datos de este estudio. Resultados: La enzima aspartato-aminotransferasa (AST) estaba aumentando en mayor prevalencia, con un total de 4695 casos, mientras que la alanina-aminotransferasa (ALT) estaba elevada en 3226 casos. Se observa que los pacientes que presentaban síntomas digestivos tenían más probabilidades de presentar daño hepatocelular y, en consecuencia, alteraciones enzimáticas. Además, la mortalidad ocurrió en el 28,9 % de los casos de pacientes con función hepática alterada, mientras que, en aquellos con función normal, esta tasa fue del 9 %. Conclusión: es evidente que existe una relación entre la afectación hepática por COVID-19 y su mortalidad. Sin embargo, todavía existe una limitación en la cantidad y, principalmente, en la homogeneidad de los estudios que realizaron dicha valoración.

Abstract Introduction: In March 2020, the World Health Organization declared COVID-19, a disease caused by SARS-CoV-2 infection, a global pandemic. This virus uses human angiotensin-converting enzyme 2 (ACE2) as its receptor for entry. ACE2 is found in pulmonary, cardiac, gastrointestinal, hepatic, renal and vascular tissues, thus posing a potential risk for multisystemic involvement. The excessive release of inflammatory cytokines in COVID-19, as well as the use of medicines with hepatotoxic potential for the treatment of its symptoms, can damage the liver. Objective: To analyze the relationship between changes in liver function tests caused by SARS-CoV-2 infection and their impact on patient prognosis. Methodology: This is a systematic review of studies selected from the PMC, LILACS and SciELO databases. After applying the inclusion and exclusion criteria, 30 articles were included in the final sample for analysis. Results: Elevated AST (aspartate aminotransferase) enzyme levels were reported most frequently and were found in 4 695 cases, while ALT (alanine aminotransferase) elevation was described in 3 226 cases. It was observed that patients with digestive symptoms were more likely to present hepatocellular damage and, consequently, enzymatic alterations. Furthermore, 28.9 % of individuals with impaired liver function died, compared to 9 % of patients with normal function. Conclusion: It is evident that there is a relationship between liver involvement in COVID-19 and mortality. However, there is still a limitation in the number and, more importantly, the homogeneity of the research that performed this assessment.

Asociación entre el espesor de la grasa subcutánea abdominal y la esteatosis hepática, las enzimas hepáticas y los lípidos séricos en niños obesos / Association of abdominal subcutaneous fat thickness with hepatic steatosis, liver enzymes, and serum lipids in obese children

Introducción. La obesidad infantil puede causar hiperlipidemia y esteatosis hepática y complicaciones crónicas. Nuestro objetivo fue evaluar la relación entre el espesor de la grasa subcutánea abdominal (GSA) y la esteatosis hepática, las transaminasas y los lípidos séricos en niños obesos.Población y métodos. Estudio retrospectivo en niños (4-18 años) que acudieron a los consultorios externos. Se evaluaron las asociaciones entre el espesor de la GSA mediante ecografía y la esteatosis hepática, alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y el perfil lipídico sérico.Resultados. Se identificaron 95 niños con esteatosis hepática; el grado 1 fue el más frecuente (73,6 %, n: 70), seguido del grado 2 (21,1 %) y del 3 (5,3 %). El espesor medio (en mm) de la GSA de línea media y flancos fue 38,48 ± 11,53 y 20,91 ± 8,00 en grado 1; 41,23 ± 10,03 y 19,84 ± 6,75 en grado 2, y 63,12 ± 12,08 y 23,22 ± 5,92 en grado 3, respectivamente. El espesor de la GSA de línea media y flancos se correlacionó positivamente con triglicéridos en grado 3; el espesor de la GSA de línea media se correlacionó con el índice de masa corporal, colesterol total, colesterol LDL y AST (r: 0,9; p: 0,037; r: 0,648; p: 0,001; r: 0,387; p: 0,001; r: 0,406; p: 0,001; r: 0,463; p: 0,001; respectivamente) en grado 1.Conclusión. El espesor de la GSA mediante ecografía puede predecir hiperlipidemia en niños obesos con esteatosis hepática de grado 3 e hipercolesterolemia en grado 1.

Introduction. Childhood obesity can cause hyperlipidemia and hepatic steatosis at early age and chronic disease complications in adult life. We aimed to evaluate the relationship between abdominal subcutaneous fat thickness (ASFT) and hepatic steatosis, serum lipid and transaminase levels in obese children.Population and methods. A retrospective study was conducted with children (aged 4-18 years) who presented to outpatient clinic due to obesity. Associations between ASFT as assessed by ultrasonography (US) and hepatic steatosis, alanine transaminase (ALT), aspartate transaminase (AST) and serum lipid profile were evaluated.Results. We identified 95 children, all of which were diagnosed as having hepatic steatosis; the most common type was grade 1 (73.6 %, n: 70), followed by grade 2 (21.1 %) and grade 3 (5.3 %). The mean values of midline and flank ASFT were measured as 38.48 ± 11.53 mm and 20.91 ± 8.00 mm in grade 1; 41.23 ± 10.03 and 19.84 ± 6.75 in grade 2 and 63.12 ± 12.08 and 23.22 ± 5.92 in grade 3 hepatic steatosis, respectively. Midline and flank ASFT correlated positively with triglycerides in grade 3 steatosis, while midline ASFT correlated with body mass index, total cholesterol, low-density lipoprotein cholesterol, and AST (r: 0.9; p: 0.037; r: 0.648, p: 0.001; r: 0.387, p: 0.001; r: 0.406, p: 0.001, r: 0.463, p: 0.001; respectively) in grade 1 steatosis.Conclusion. ASFT as assessed by US may be of predictive value for hyperlipidemia in grade 3 and for hypercholesterolemia in grade 1 hepatic steatosis in obese children.

Uso de corticosteroides no tratamento da lesão hepática aguda grave decorrente de anabolizante estanazolol / Use of corticosteroids in the treatment of stanazolol-induce severe acute liver injury

A busca pelo corpo perfeito pode gerar graves consequências para a população que faz uso indiscriminado de substâncias visando a resultados rápidos. O caso relatado se refere a um pa- ciente de 21 anos, do sexo masculino, na cidade de São Paulo (SP), que apresentou quadro de síndrome colestática 15 dias após uso do anabolizante estanazolol para fins estéticos na ativi- dade física, evoluindo com hepatite medicamentosa grave, com aumento de transaminases, hiperrubilinemia às custas de bilirrubina direta e fatores de coagulação, sem resposta satis- fatória ao tratamento de suporte convencional, com melhora significativa após introdução de corticoterapia.

Searching for the perfect body image can cause severe conse- quences to the population using substances indiscriminately to reach results fast. The case reported refers to a male patient, 21 years old, from the city of São Paulo (SP), who developed choles- tatic syndrome 15 days after the use of the steroid Stanazol for aesthetic purposes during physical activity, progressing with se- vere drug-induced hepatitis, transaminases, bilirubin, and coagu- lation factors increase with no satisfactory response to the con- ventional support treatment, and significant improvement after the introduction of corticotherapy.

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.

Variante "no clásica" o "atípica" del síndrome de Stauffer en paciente con carcinoma renal de células claras: reporte de caso / "Non-classical" or "atypical" variant of Stauffer syndrome in a patient with clear cell renal carcinoma: a case report

La manifestación paraneoplásica conocida como síndrome de Stauffer tiene una presentación atípica, caracterizada por ictericia y colestasis intrahepática. Presentamos el caso de un paciente de 53 años de edad, con antecedente de una masa renal derecha en plan de resección quirúrgica programada, con cuadro de evolución de dolor abdominal en hipocondrio derecho e ictericia. A su ingreso se documentó hepatoesplenomegalia, elevación de bilirrubinas a expensas de la directa, y de fosfatasa alcalina junto con elevación de transaminasas. Se descartaron causas obstructivas a nivel de vía biliar intra y extrahepática. No se documentaron metástasis o lesiones focales a nivel de parénquima, ni lesiones de etiología vascular que explicaran el cuadro. También se descartó hepatitis B, C e infección por VIH, por lo cual se consideró un probable síndrome de Stauffer. Fue llevado a nefrectomía intrahospitalaria, con posterior diagnóstico patológico compatible con carcinoma de células claras. Luego del procedimiento se normalizó la bioquímica hepática y se corrigió la ictericia. Es importante reconocer que la afectación hepática en el contexto de neoplasias, no es solo atribuida a metástasis a distancia, sino también a la existencia de síndromes paraneoplásicos como condicionantes.

The paraneoplastic manifestation known as Stauffer syndrome has an atypical presentation, characterized by jaundice and intrahepatic cholestasis. We present the case of a 53-year-old patient, with a history of a right renal mass with a planned surgical resection, who developed abdominal pain in the right upper quadrant and jaundice. Upon admission, hepatosplenomegaly, elevated bilirubin, at the expense of direct bilirubin, alkaline phosphatase and elevated transaminases were documented. Intra- and extrahepatic bile ducts obstruction were ruled out. There were no documented metastases or focal lesions at the level of the parenchyma, or lesions of vascular etiology that could explain the condition. Hepatitis B, C and HIV infection were also ruled out, and a probable Stauffer syndrome was considered. In-hospital nephrectomy was performed, with subsequent pathology compatible with clear cell carcinoma. After the procedure, liver biochemistry was normalized and jaundice was corrected. It is important to recognize that liver involvement in the context of neoplasms is not only attributed to distant metastases but to the existence of paraneoplastic syndromes as determining factors.

Elevación de las aminotransferasas: una nueva herramienta para el diagnóstico de coledocolitiasis. Un estudio de casos y controles / Elevated transaminases: a new tool for the diagnosis of choledocholithiasis. A case control study

Resumen Introducción: la coledocolitiasis (CDL) afecta al 10 % de los pacientes con cálculos en la vesícula biliar. La obstrucción del colédoco se asocia a pancreatitis, colangitis y ruptura del colédoco. Clásicamente, la obstrucción biliar es considerada cuando se aumentan la fosfatasa alcalina, la γ-glutamil-transpeptidasa (GGTP) y las bilirrubinas. En la última década, se ha encontrado que hasta un 10 % de los pacientes con CDL presentan elevaciones de las aminotransferasas. En Latinoamérica, no se ha estudiado esta alteración. El objetivo del presente trabajo fue determinar la prevalencia de la elevación de transaminasas y su evolución. Metodología: estudio de casos y controles. Se determinó la alanina aminotransferasa (ALT) al ingreso, a las 48 h y a las 72 h. Si la ecografía era normal, se realizó una colangiorresonancia o una ecoendoscopia, así como una colangiopancreatografía retrógrada endoscópica (CPRE) cuando fue necesario. Resultados: se incluyeron 72 pacientes con CDL (casos) y 128 con colecistitis, sin CDL (controles). En los casos, el 83 % tuvo un aumento de ALT, mientras que el 56,9 % presentó una elevación de 2-9 veces, el 16 %, de 10-20 veces, y el 8,3 % mostró una elevación >20 veces. En contraste, a las 48 h, las ALT descendieron al 30 % y a las 72 h al 56 %. Entre tanto, en los controles hubo un aumento de ALT en el 27,3 %, mientras que en el 15,6 % se observó una elevación de 2-9 veces, en el 7,8 %, de 10-20 veces, y >20 veces en el 2,9 %. La combinación de cólico biliar y la elevación de ALT tuvo un valor predictivo positivo (VPP) para CDL del 72 %, así como un valor predictivo negativo (VPN) del 87,7 %. Conclusión: cuando hay un cólico biliar y una elevación de ALT es imperativo descartar una CDL, y si la ecografía es normal, es necesario realizar una colangiorresonancia o una ecoendoscopia biliopancreática.

Abstract Introduction: Choledocolithiasis (CLD) affects 10% of patients with gallstones. Bile duct obstruction is associated with pancreatitis, cholangitis, and rupture of the common bile duct. This condition usually presents with increased alkaline phosphatase, GGTP and bilirubin levels. In the last decade, it has been found that up to 10% of patients with CLD have elevated aminotransferases levels. In Latin America, this alteration has not been studied. The aim of the present work was to determine the prevalence of transaminase elevation and its evolution. Methodology: Case-control study. ALT was measured on admission, at 48 h and at 72 h. If ultrasound was normal, MRCP and/or echo-endoscopy and ERCP were performed, as appropriate. Results: A total of 72 patients with choledocholithiasis (CLD) (cases) and 128 with cholecystitis without choledocholithiasis (controls) were included. Among the cases, 83% had increased ALT levels, which was 2-9 times higher in 56.9%, 10-20 times higher in 16%, and more than 20 times higher in 8.3%. At 48 hours, those levels decreased by 30% and at 72 hours by 56%. In turn, in 27.3% of the controls, ALT was 2-9 times higher in 15.6%, 10-20 times higher in 7.8% and more than 20 times higher in 2.9%. The combination of biliary colic and ALT elevation had a positive predictive value (PPV) for CLD of 72% and a negative predictive value (NPV) of 87.7%. Conclusion: When biliary colic and ALT elevation are reported, it is imperative to rule out choledocholithiasis. If the ultrasound is normal, MRCP and/or biliopancreatic endoscopy should be performed.

Sífilis congénita resultado de una Neurosífilis materna no diagnosticada. Reporte de caso / Congenital syphilis due to undiagnosed maternal neurosyphilis: case report

Resumen En el mundo, se ha evidenciado un aumento de los casos de sífilis, de sífilis gestacional y de sífilis congénita. Se presenta el caso de un recién nacido con sífilis congénita, hijo de una madre con sífilis latente de duración indeterminada (VDRL 1:4 diluciones) diagnosticada y tratada a la semana 12 de gestación, VIH negativa, con compañero seronegativo para sífilis; a pesar del tratamiento con tres dosis de 2'400 000 U de penicilina benzatínica, no modificó los títulos del VDRL ni en el control de la semana 25 de gestación, ni en el momento del parto. En el posparto, la madre fue diagnosticada con neurosífilis y recibió tratamiento con penicilina cristalina durante 14 días. El recién nacido fue diagnosticado con sífilis congénita por presentar VDRL 1:4 diluciones, aumento de aminotransferasas, hematuria y proteinuria, recibiendo tratamiento con penicilina cristalina durante 10 días. La paciente evolucionó favorablemente y el control a los 6 meses fue normal. Deben fomentarse medidas útiles en la prevención de la sífilis gestacional: métodos de barrera, conocimiento de la enfermedad y asistencia a control prenatal. Es fundamental identificar y tratar a las gestantes con sífilis mediante tamizaje serológico para prevenir la sífilis congénita; el seguimiento serológico debe ser estricto para verificar la eficacia del tratamiento e investigar las gestantes que no modifican los títulos después del tratamiento. MÉD.UIS.2020;33(1):73-80.

Abstract In the world, there has been an increase in cases of syphilis, gestational syphilis and congenital syphilis. It's presented the case of a newborn with congenital syphilis, son of a mother with latent syphilis of indeterminate duration (VDRL 1: 4 dilutions) diagnosed and treated at week 12 of gestation, HIV negative, with seronegative partner for syphilis; despite treatment with three doses of 2'400 000 U of benzathine penicillin, the VDRL titres remained unaltered on both the control of the 25th week of gestation and at the time of delivery. The mother, in the postpartum period, was diagnosed with neurosyphilis and was treated with crystalline penicillin for 14 days. The newborn was diagnosed with congenital syphilis by presenting 1:4 VDRL dilutions, increased aminotransferases, hematuria and proteinuria; he was treated with crystalline penicillin for 10 days. Useful measures should be promoted in the prevention of gestational syphilis such as barrier methods, knowledge of the disease and assistance to prenatal control. It is mandatory to identify and treat pregnant women with syphilis by serological screening for the disease in order to prevent congenital syphilis. Serological follow-up should be strict to verify the effectiveness of the treatment and to investigate pregnant women who do not modify the titres after treatment. MÉD.UIS.2020;33(1):73-80.

Effect of low-fat diets enriched with fruit purees on the biochemical markers of metabolic syndrome analogy induced-rats / Efecto de dietas bajas en grasa enriquecida con purés de frutas sobre marcadores bioquímicos en ratas inducidas con analogia a sindrome metabólico

Fruit purees can be added to diet as alternative sources of bioactive compounds for the prevention and/or improvement of the complications of metabolic syndrome. In this work we evaluated the effect of the intake of low-fat diets enriched with fruit purees (guava-strawberry, guava-blackberry, guava-soursop, guava-passion fruit) on the body weight and biochemical markers in metabolic syndrome analogy (MSA)-induced rats. The rats (n=6 for each treatment) were induced with a high fat diet and were injected with streptozotocin, one dose every week for 4 consecutive weeks after fasting overnight, then healthy rats were fed with standard diet and MS rats were fed with standard diet plus each of the fruit puree, for 4 weeks. As novel findings, the diet enriched with fruit purees was associated with a reduction in body weight (~13-21 %) and a control in the metabolism of glucose by decreasing plasma glucose (~5963 %). Also, there was a reduction in the total cholesterol, triacylglycerols, low-density lipoproteins, and low enzymatic activities of alanine aminotransferase, alkaline phosphatase and γ-glutamyl transferase, useful metabolites in the control of inflammatory processes in the liver. A notable improvement in the liver morphology was observed indicating that the treatments had a hepatoprotective effect. The diet enriched with guava-blackberry puree caused the best results on most biochemical markers of MS rats. Therefore, diets enriched with fruit purees can be an alternative for MS individuals for the control and improvement of the complications caused by this syndrome.

Los purés de frutas se pueden agregar a la dieta como fuentes alternativas de compuestos bioactivos para la prevención y / o mejora de las complicaciones del síndrome metabólico. En este trabajo evaluamos el efecto de la ingesta de dietas bajas en grasas, enriquecidas con purés de frutas (guayaba-fresa, guayaba-mora, guayaba-guanábana, guayaba-maracuyá) sobre el peso corporal y los marcadores bioquímicos en el síndrome metabólico (SM) inducido en ratas. Las ratas (n = 6 para cada tratamiento) fueron inducidas con una dieta alta en grasas y se les inyectó estreptozotocina, una dosis cada semana durante 4 semanas consecutivas después de ayunar durante la noche. Luego, las ratas sanas fueron alimentadas con una dieta estándar; y las ratas con SM fueron alimentadas con dieta estándar más cada uno de los purés de frutas, durante 4 semanas. Como hallazgos novedosos, la dieta enriquecida con purés de frutas se asoció con una reducción en el peso corporal (~ 13-21 %) y un control en el metabolismo de la glucosa al disminuir la glucosa en plasma (~ 59-63 %). Además, hubo una reducción en el colesterol total, triacilgliceroles, lipoproteínas de baja densidad, y bajas actividades enzimáticas de alanina aminotransferasa, fosfatasa alcalina y gama-glutamil transferasa, metabolitos útiles en el control de los procesos inflamatorios en el hígado. Se observó una mejora notable en la morfología del hígado, lo que indica que los tratamientos tuvieron un efecto hepatoprotector. La dieta enriquecida con puré de guayaba y mora causó los mejores resultados en la mayoría de los marcadores bioquímicos de las ratas con SM. Por lo tanto, las dietas enriquecidas con purés de frutas pueden ser una alternativa para las personas con SM, para el control y la mejora de las complicaciones causadas por este síndrome.

Evaluation of adult celiac disease from a tertiary reference center: a retrospective analysis

SUMMARY OBJECTIVE It has been observed that celiac disease (CD) is not restricted to a single type characterized by diarrhea but also has atypical, asymptomatic (silent), and latent forms. The prevalence of this autoimmune disease, which affects approximately 1% of the world, is estimated to be around 3%, including atypical and asymptomatic cases. In our study, we aimed to evaluate adult celiac patients. METHODS Between December 2008-2015, patients diagnosed with CD over the age of 18 years old were included in the study. Patients' symptoms at admission, frequency and type of anemia, transaminase levels, and celiac antibody positivity, and autoimmune diseases diagnosed at follow up were evaluated retrospectively. RESULTS Of 195 patients, 151 (77.4%) were female. The mean age of the patients was 35.73 ± 12.19 years (range, 18-71 years). A hundred patients (51.3%) had gastrointestinal symptoms. At the time of admission, 118 patients (60.5%) had anemia, and 52 (26.7%) had hypertransaminasemia. During the mean follow-up period of 58 months (36-120 months), 84 (43.1%) of the patients presented at least one autoimmune disease, and this rate was 96.6% in individuals diagnosed above the age of 50 years. CONCLUSION In adult CD, resistant anemia, dyspepsia, and hypertransaminasemia are very common findings at the time of diagnosis, and the association with other autoimmune diseases, especially Hashimoto's thyroiditis, is high.

RESUMO OBJETIVOS Observou-se que a doença celíaca (DC) não se restringe a um único tipo caracterizado por diarreia, mas também tem formas atípicas, assintomáticas (silenciosas) e latentes. Estima-se que a prevalência desta doença autoimune, que afeta aproximadamente 1% da população do mundo, seja em torno de 3%, incluindo casos atípicos e assintomáticos. Em nosso estudo, objetivou-se avaliar pacientes celíacos adultos. MÉTODOS Entre dezembro de 2008 e 2015, pacientes diagnosticados como DC com idade acima de 18 anos foram incluídos no estudo. Os sintomas dos pacientes na admissão, frequência e tipo de anemia, níveis de transaminases e positividade de anticorpos celíacos e doenças autoimunes diagnosticadas no seguimento foram avaliados retrospectivamente. RESULTADOS Dos 195 pacientes, 151 (77,4%) eram do sexo feminino. A média de idade dos pacientes foi de 35,73±12,19 anos (variação de 18 a 71 anos). Cem pacientes (51,3%) foram encaminhados com sintomas gastrointestinais. No momento da internação, 118 pacientes (60,5%) apresentavam anemia e 52 (26,7%) apresentavam hipertransaminemia. Durante o período médio de acompanhamento de 58 meses (36-120 meses), 84 (43,1%) pacientes estavam acompanhados por pelo menos uma doença autoimune, e essa taxa foi de 96,6% em indivíduos diagnosticados acima dos 50 anos de idade. CONCLUSÃO No adulto DC, anemia resistente, dispepsia e hipertransaminasemia são achados muito comuns no momento do diagnóstico e a associação com outras doenças autoimunes, especialmente tireoidite de Hashimoto, é alta.

Angiomiolipoma renal con invasión de vena renal y vena cava inferior. Presentación de un caso y revisión de la literatura / Renal Angiomyolipoma with Extension to Renal and Cava Veins. A Case Report and Revision of the Literature

Introducción El angiomiolipoma es un tumor benigno cuya presentación con invasión del seno renal y formación de trombo venoso tumoral es muy infrecuente, habiéndose descrito aproximadamente 50 casos desde que en 1982 Kutcher describiera el primero. Reporte de caso Presentamos un caso angiomiolipoma renal con afectación venosa diagnosticado mediante TAC a partir del hallazgo de trombo venoso en ecografía y resonancia en una paciente de 43 años embarazada y asintomática que presentó elevación de transminasas en una analítica. Ante la posibilidad de que se tratara de una variante epitelioide y/o clásica con potencial de malignización, se decidió tratamiento mediante nefrectomía y trombectomía abierta, sin incidencias intra ni postoperatorias. La paciente se encuentra asintomática tras 6 meses de seguimiento. La histología fue compatible con angiomiolipoma clásico con trombo venoso. Conclusión La invasión de vena renal por un angiomiolipoma es extremadamente rara. Aunque infrecuente, habría que considerar la posibilidad de malignización para no demorar su tratamiento

Introduction Angiomyolipoma is a benign kidney tumour that rarely affects the renal sinus or the renal or caval vein. Kutcher made the first case report in 1982, and since then there have been described approximately 50 cases. Case Report We present a case of angiomyolipoma with venous thrombus in a 43 years-old asymptomatic pregnant woman who presented elevation of transaminases in a blood test, with an ultrasonography that showed a venous thrombus without any renal mass, being diagnosed after giving birth by scanner. Having in account the possibility of malignancy of the mass, we performed surgical treatment by open radical nephrectomy and thrombectomy, without intraoperative nor postoperative incidences. The patient remains asymptomatic 6 months after surgery. The histology was compatible with classic angiomyolipoma with venous thrombus. Conclussion Angiomyolipoma causing venous invasion is extremely rare, but we should take into consideration its possibility of malignancy in order to treat it as soon as possible

A dúvida: tireotoxicose versus hipertireoidismo descompensado / The doubt: Thyrotoxicosis X Decompensated Hyperthyroidism

Relata-se o caso de paciente do sexo masculino, atendido em um hospital universitário, após quadro duvidoso e arrastado de alteração cardíaca e hipertireoidiana, com a propedêutica sequencial própria para crise tireotóxica. Destaca-se a necessidade de identificação precoce da apresentação clínica, com atendimento de emergência, e a capacidade da realização de diagnósticos diferenciais com alterações cardíacas primárias, evitando-se sequelas e desfechos inesperados.

We report the case of a male patient seen in a University Hospital after a dubious and protracted picture of cardiac and hyperthyroid alteration, with adequate sequential propaedeutic for thyrotoxic crisis. The need for early identification of clinical presentation with emergency care, and the ability to perform differential diagnoses with primary cardiac changes are highlighted, to avoid unexpected sequelae and outcomes.

Protección renal y hepática por condicionamiento isquémico a distancia en la revascularización miocárdica quirúrgica / Renal and hepatic protection due to remote ischemic conditioning in coronary artery bypass grafting

RESUMEN Introducción: Breves períodos de isquemia a distancia pueden limitar el daño miocárdico producido por la isquemia/reperfusión. Objetivos: Identificar el efecto del condicionamiento isquémico a distancia con fines de protección renal y hepática, relacionado al comportamiento postoperatorio de los niveles de creatinina y transaminasas glutámico-purúvica y glutámico-oxalacética en la revascularización miocárdica quirúrgica. Método: Se realizó un estudio cuasiexperimental, explicativo, comparativo con control histórico, en dos grupos de 247 pacientes cada uno, propuestos para revascularización miocárdica quirúrgica. Se colocó un torniquete en el brazo derecho, en el grupo estudio, alternando 3 insuflaciones (con una presión de 200 mmHg) con 3 desinsuflaciones, durante cinco minutos cada una. Este procedimiento se realizó previo, durante y después de la mayor isquemia inducida, provocada por el pinzamiento de la arteria coronaria. Resultados: Se logró una disminución significativa en los valores de creatinina (p<0,001), transaminasa glutámico-purúvica (p<0,001) y transaminasa glutámico-oxalacética (p<0,05). Conclusiones: El condicionamiento isquémico a distancia es una importante herramienta a tener en cuenta para la protección renal y hepática en la revascularización miocárdica quirúrgica.

ABSTRACT Introduction: Short periods of distant ischemia can limit myocardial damage caused by ischemia/reperfusion. Objective: To identify the effect of remote ischemic preconditioning in relation to the postoperative behavior of creatinine, glutamic transaminase, puruvic and oxalacetic levels. Method: A quasi-experimental, explanatory, comparative study with historical control was carried out in two groups of 247 patients each; all candidates for coronary artery bypass grafting. A blood-pressure cuff was placed on the right arm in the study group alternating three inflations with three deflations of five minutes at 200 mmHg. This procedure was performed prior to during and after the major ischemic episode caused by the coronary artery impingement. Results: A significant decrease in the values ​​of creatinine, puruvic glutamic transaminase and glutamic oxalacetic transaminase was achieved. Conclusions: Remote ischemic conditioning is an important tool to take into account for renal and hepatic protection in coronary artery bypass grafting.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

ABSTRACT Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Local and systemic effects caused by Crotalus durissus terrificus, Crotalus durissus collilineatus, and Crotalus durissus cascavella snake venoms in swiss mice

Abstract INTRODUCTION: Crotalus envenomations cause serious complications and can be fatal without appropriate treatment. Venom isoforms present and inter/intraspecific variations in the venom composition can result in different symptoms presented by bites by snakes from the same species but from different geographical regions. We comparatively evaluated the local and systemic effects caused by Crotalus durissus terrificus (Cdt), C.d. collilineatus (Cdcolli), and C.d. cascavella (Cdcasc) envenomation. METHODS: Venom chromatography was performed. Proteolytic, phospholipase, and LAAO activities were analyzed. Edema, myotoxicity, hepatotoxicity, nephrotoxicity, and coagulation alterations were evaluated. RESULTS: The venom SDS-PAGE analyses found the presence of convulxin, gyroxin, crotoxin, and crotamine in Cdt and Cdcolli venoms. Crotamine was not present in the Cdcasc venom. Cdt, Cdcollli, and Cdcasc venoms had no proteolytic activity. Only Cdcasc and Cdt venoms had phospholipase activity. LAAO activity was observed in Cdcolli and Cdcasc venoms. Cdcolli and Cdcasc venoms caused 36.7% and 13.3% edema increases, respectively. Cdt venom caused a 10% edema induction compared to those by other venoms. All venoms increased TOTAL-CK, MB-CK, and LDH levels (indicating muscle injury) and ALT, AST, GGT, and ALP levels (markers of liver damage) and were able to induce a neuromuscular blockade. Urea and creatinine levels were also altered in both plasma and urine, indicating kidney damage. Only Cdcolli and Cdcasc venoms increased TAPP and TAP. CONCLUSIONS: Together, these results allow us to draw a distinction between local and systemic effects caused by Crotalus subspecies, highlighting the clinical and biochemical effects produced by their respective venoms.

Isolation and partial characterization of a new moderate thermophilic Albidovulum sp. SLM16 with transaminase activity from Deception Island, Antarctica

BACKGROUND: A moderately thermophilic, slightly halophilic, aerobic, Gram-stain negative, bacterial strain, SLM16, was isolated from a mixed of seawater-sand-sediment sample collected from a coastal fumarole located in Whalers Bay, Deception Island, Antarctica. The aim was to screen for thermophilic microorganisms able to degrade primary amines and search for amine transaminase activity for potential industrial application. RESULTS: Identification and partial characterization of the microorganism SLM16 were carried out by means of morphological, physiological and biochemical tests along with molecular methods. Cells of strain SLM16 were non-motile irregular rods of 1.5-2.5 µm long and 0.3-0.45 µm wide. Growth occurred in the presence of 0.5-5.5% NaCl within temperature range of 35-55 °C and pH range of 5.5-9.5, respectively. The DNA G+C composition, estimated from ftsY gene, was 66% mol. Phylogenetic analysis using de 16S rRNA gene sequence showed that strain SLM16 belongs to the marine bacterial genus Albidovulum. CONCLUSION: Strain SLM16 is a moderate thermophilic Gram negative microorganisms which belongs to the marine bacterial genus Albidovulum and is closely related to Albidovulum inexpectatum species based on phylogenetic analysis. Additionally, amine-transaminase activity towards the arylaliphatic amine α-methylbenzylamine was detected.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.