Trasplante cardíaco por hemocromatosis. Caso pediátrico / Cardiac transplantation due to hemochromatosis. A pediatric case report

La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.

Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.

Cenário das políticas públicas para hemocromatose hereditária no Brasil / Public policy scenario for hereditary hemochromatosis in Brazil

Resumo Hemocromatose hereditária (HH) é a doença genética mais comum em descendentes de europeus e sua epidemiologia em nosso país é incerta. Considerando o cenário das políticas públicas em HH no mundo contemporâneo, este artigo propõe uma reflexão sobre o tema, com objetivo de fazer uma revisão bibliográfica narrativa sobre a abordagem adotada para essa doença em países desenvolvidos e a nível nacional. Além disso, discute sobre o custo-benefício da incorporação do índice de saturação da transferrina (ST) e ferritina sérica (FS) no nosso sistema de saúde, com a finalidade de identificar a HH antes que surjam suas complicações, bem como seu rastreio em campanhas nacionais de prevenção. O valor gasto para o screening da HH com dosagem de ST e FS pelo Sistema Único de Saúde (SUS) é muito menor do que os custos gerados quando o dano por excesso de ferro já está estabelecido. Nos casos suspeitos de HH, deveria ser viabilizada pelo SUS a pesquisa da mutação genética para o gene HFE, que atualmente só está disponível de forma privada. Com essas medidas, modifica-se a história natural da doença, reduzindo a morbimortalidade dos portadores e custos ao sistema público de saúde.

Abstract Hereditary hemochromatosis (HH) is the most common genetic disease among European descendants and its epidemiology in Brazil is unclear. Considering the contemporary public policy scenario aimed at HH, this narrative bibliographic review reflects on the approach adopted for this disease at the national level in developed countries. It also discusses the cost-effectiveness of incorporating transferrin saturation (TS) and serum ferritin (SF) indexes in the Brazilian healthcare system for early HH identification, as well as its screening in national prevention campaigns. The amount spent on ST- and FS-based HH screening by the Brazilian National Health System (SUS) is much lower than the costs generated by the already established iron overload. In suspected cases, genetic mutation research of the HFE gene, which is currently only performed privately, should be made available by the SUS. These measures can modify the natural history, reducing HH morbidity and mortality and its costs to the public health system.

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.

Recognition of Iron Overload Cardiomyopathy / 罕见病研究

Iron overload cardiomyopathy (IOC) is a type of cardiac dysfunction caused by several factors resulting in iron overload in the myocardium. Two major causes of IOC include hereditary hemochromatosis and transfusion-dependent anemia. IOC significantly reduces long-term survival of patients. Since IOC is a rare disease in Asian populations that also lacks etiology-specific manifestations, early diagnoses in clinical practice are challenging. Two groups of patients with high risk of IOC should be further investigated: those who present heart failure of unknown origin will be screened for iron overload followed by confirmation of IOC; and those who have high risk of iron overload or an established diagnosis will be monitored for the development of IOC. Serum ferritin is recommended as the first-line screening test for iron overload, while cardiac magnetic resonance T2* should be used to confirm iron overload in the myocardium. Phlebotomy and iron chelating agents can effectively remove the extra iron from the body, preventing IOC, as well as reverse the disease at an early stage and slow down its progession. Timely diagnosis and treatment is critical in improving the prognosis of patients with IOC. Therefore, this review aims to help clinicians to understand IOC in multiple dimensions including pathogenesis, clinical manifestations, diagnostic methods and treatment choices.

Hemocromatosis: revisión de la literatura a propósito de un caso clínico / Hemochromatosis: case report and literature review

Hemochromatosis (HC) is a disorder that alters the body's ability to metabolize iron, increasing its absorption, causing iron overload, and consequently an accumulation of the mineral in multiple organs such as the liver, heart, and pancreas. The amount of total iron in the body is 2-4 g in healthy individuals and remains within these limits throughout life thanks to the control of intestinal absorption. In patients with CH, this amount is increased by at least 10 times, which translates into body deposits of 20-40 grams of iron on average. Factors that increase the risk of having HC: having two copies of the mutated HFE gene, family history, ethnicity or ancestry from Northern Europe (less common in blacks, Hispanics, and Asians), and male gender.

HFE hemochromatosis: an overview about therapeutic recommendations

Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.

Pedigree analysis of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene / 中华内分泌代谢杂志

Objective:To investigate clinical phenotypes of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene and the correlation between genotype and phenotype, exploring ferritin cutoff value for screening.Methods:One case of type Ⅳ hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene and 5 generations of their family lineage with a total of 47 members who were seen at the First Affiliated Hospital of Nanjing Medical University in July 2020 were studied for systematic clinical investigation. Thirty-nine surviving individuals were tested for ferritin, liver function, fasting plasma glucose (FPG), and sex hormones, and Sanger sequencing was performed to verify the mutation loci and to map the family tree. Spearman correlation analysis was used to explore the relationship between ferritin and other indicators, and receiver operating characteristic curves were used to calculate the ferritin cutoff value for screening for this genotype of hemochromatosis.Results:Ten patients with c. 430A>G heterozygous mutation in the SLC40A1 gene were identified among 39 family members, and five of them were diagnosed with hemochromatosis, presenting incomplete penetrance. The differences in levels of ferritin, aspartate aminotransferase (AST; both P<0.01) and FPG, as well as incidences of hypogonadotropic hypogonadism and arthritis (all P<0.05) between group of mutation positive and group negative were statistically significant, while the difference in alanine aminotransferase (ALT) was not. Spearman correlation analysis showed that, ferritin levels were significantly associated with ALT ( r=0.903), AST ( r=0.879), FPG ( r=0.782), and the incidences of hypogonadotropic hypogonadism ( r=0.798) and arthritis ( r=0.798; all P<0.01) in those with the c. 430A>G heterozygous mutation in the SLC40A1 gene. The ferritin cutoff value for screening of hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene was 1 036.7 μg/L, with a sensitivity and specificity of 100% and 94.3%, respectively. Conclusion:The SLC40A1 gene c. 430A>G heterozygous mutation is closely associated with elevated levels of AST and FPG, increased incidences of hypogonadotropic hypogonadism and arthritis, and the ferritin cutoff value is a useful screening parameter.

Hemocromatosis no ligada al gen HFE: a propósito de un caso / Non-HFE hemochromatosis: a case report

RESUMEN La hemocromatosis hereditaria (HH) consiste en una sobrecarga progresiva de hierro que conlleva a un acúmulo anormal del mismo en diferentes órganos blancos; y, que, en caso de no tratarse a tiempo, puede causar una disfunción multi-orgánica. Se han descrito diversas mutaciones genéticas asociadas a la HH, la más frecuente de ellas es la asociada al gen-HFE, la cual se encuentra en el 90% de los casos. En la actualidad la flebotomía terapéutica continúa siendo el tratamiento de elección para el manejo de esta patología. Reportamos el caso de un paciente en seguimiento por fibrosis hepática severa, con persistencia de un perfil ferrocinético elevado, a quien cinco años después se le diagnostica una HH no asociada a una mutación en el gen-HFE; recibió manejo con flebotomías periódicas, presentando rápidamente una mejoría significativa de su cuadro clínico y de los niveles de ferritina al igual que otros paraclínicos.

ABSTRACT Hereditary hemochromatosis (HH) consists of a progressive iron overload that leads to an abnormal accumulation of iron in different target organs; and, if not treated in time, can cause multi-organ dysfunction. Various genetic mutations associated with HH have been described, the most frequent is associated with the HFE-gene, which is found in 90% of cases. At present, therapeutic phlebotomy continues to be the treatment of choice for the management of this pathology. We report the case of a patient under follow-up for severe liver fibrosis, with persistence of a high ferrokinetic profile, who five years later was diagnosed with HH not associated to a mutation in the HFE-gene; He was managed with periodic phlebotomies, rapidly presenting a significant clinical improvement and decrease of ferritin levels.

Aspectos relevantes en hemocromatosis hereditaria / Relevant features in hereditary hemochromatosis

La hemocromatosis hereditaria es una enfermedad que se caracteriza por la sobrecarga sistémica de hierro y se asocia a múltiples mutaciones genéticas que conducen a una producción inadecuadamente baja de la hormona hepcidina o a una alteración en la unión de la hepcidina a la ferroportina. Esto tiene como resultado un aumento de la absorción intestinal y el depósito de cantidades excesivas de hierro en las células, lo cual, a su vez, si no se corrige, genera daño tisular. La expresión clínica puede variar desde individuos completamente asintomáticos, hasta pacientes con cirrosis hepática a temprana edad, y eventualmente carcinoma hepatocelular. Habitualmente, el diagnóstico no es invasivo e incluye el examen clínico, la evaluación de los parámetros de hierro plasmático, imágenes y pruebas genéticas. El principal tratamiento es la flebotomía, pero terapias alternativas como la suplementación con hepcidina son un tema de investigación actual.

Hereditary hemochromatosis is a disease characterized by systemic iron overload of genetic origin, that leads to an inadequately low production of the hormone hepcidin or a reduction in hepcidinferroportin binding. This results in an increased intestinal absorption and the deposit of excessive amounts of iron in cells, which in turn results in tissue damage if not treated. The clinical expression can vary from completely asymptomatic individuals, to patients with liver cirrhosis at an early age, and eventually hepatocellular carcinoma. Diagnosis is usually noninvasive and includes clinical examination, assessment of plasma iron levels, imaging studies, and genetic testing. The main medical treatment is phlebotomy, but alternative therapies such as hepcidin supplementation are the subject of current research.

Hereditary hemochromatosis associated with the development of liver cirrhosis / Hemocromatose hereditária associada ao desenvolvimento da cirrose hepática

ABSTRACT Hereditary hemochromatosis (HH) is an autosomal recessive disease, most often associated with mutations in the HFE gene, which result in continuous absorption of iron, causing its overload. Liver tissue is the main site of iron deposition; thus, high levels of iron, when interacting with oxygen, induce the formation of free radicals that will act on proteins, lipids, and deoxyribonucleic acid (DNA), which may trigger deleterious effects at cellular and tissue levels. In order to elucidate the development and progression of liver cirrhosis due to iron overload, the purpose of this study is to describe the pathophysiology of the hepatic system in patients diagnosed with HH. For this purpose, searches for scientific articles were carried out in the main academic databases. We found that patients diagnosed with HH are more likely to develop liver cirrhosis, since chronic iron deposition in liver tissue induces injury and consequent tissue regeneration, progressing to collagen fibers synthesis surrounding the hepatocytes, leading to loss of liver function and development of cirrhosis. Therefore, it is necessary to carry out tests such as iron, ferritin and transferrin measurements, to evaluate body's iron stores, aiming at an early diagnosis of iron overload, thus avoiding deleterious damage at cellular and tissue levels.

RESUMEN La hemocromatosis hereditária (HH) es uma enfermedad autosómica recesiva, asociada, la mayoría de las veces, a mutaciones del gen HFE, que producen absorción continua de hierro, con sobrecarga de esa sustancia. El tejido hepático es el principal sitio de almacenamiento de hierro; así, niveles elevados de hierro, al interactuar con oxígeno, inducen la formación de radicales libres que actuarán sobre proteínas, lípidos y ácido desoxirribonucléico (ADN), pudiendo acarrear efectos dañosos a nível celular y tisular. Para aclarar el mecanismo de desarrollo de la cirrosis hepática debido a sobrecarga de hierro, el objetivo de este estudio es describir la fisiopatologia del sistema hepático en pacientes diagnosticados con HH. Para eso, se efectuaron búsquedas por artículos científicos en los principales bancos de datos acadêmicos. Verificamos que pacientes diagnosticados con HH presentan mayor predisposición a desarrollar cirrosis hepática, porque el depósito crônico de hierro en el tejido hepático causa lesión y consecuente regeneración de tejido, progresando a la formación de fibras de colágeno que rodean los hepatocitos, llevando la pérdida de la función hepática y al desarrollo de la cirrosis. Ante esto, es necesario medir hierro, ferritina y transferrina para evaluación de las provisiones de hierro del cuerpo, buscando un diagnóstico temprano de la sobrecarga de hierro, para evitar efectos deletereos a nível celular y tisular.

RESUMO A hemocromatose hereditária (HH) é uma doença autossômica recessiva, associada, na maioria das vezes, a mutações do gene HFE, que resultam em absorção contínua de ferro, ocasionando a sobrecarga dessa substância. O tecido hepático é o principal sítio de depósito do ferro; dessa forma, níveis elevados de ferro, ao interagir com o oxigênio, induzem a formação de radicais livres que irão agir sobre proteínas, lipídios e ácido desoxirribonucleico (DNA), podendo desencadear efeitos deletérios a níveis celulares e teciduais. Visando elucidar o mecanismo de desenvolvimento da cirrose hepática decorrente da sobrecarga de ferro, o objetivo deste estudo é descrever a fisiopatologia do sistema hepático em pacientes diagnosticados com HH. Para isso, foram realizadas buscas por artigos científicos nos principais bancos de dados acadêmicos. Verificamos que pacientes diagnosticados com HH apresentam maior predisposição de desenvolver cirrose hepática, pois o depósito crônico de ferro no tecido hepático provoca lesão e consequente regeneração tecidual, progredindo para formação de fibras de colágeno que circundam os hepatócitos, levando à perda da função hepática e ao desenvolvimento da cirrose. Diante disso, faz-se necessária a realização de exames como dosagem de ferro, ferritina e transferrina para avaliação dos estoques de ferro do organismo, objetivando um diagnóstico precoce da sobrecarga de ferro, a fim de evitar danos deletérios a níveis celulares e teciduais.

Allelic Diversity of the Hemochromatosis Gene (HFE) in Malays, Chinese and Indians

@#Introduction: Hereditary hemochromatosis (HH) is an autosomal recessive disorder that causes accumulation of iron in circulating blood and organs. The disease is associated with H63D, S65C and C282Y variants of the haemochromatosis (HFE) gene and, if not treated can cause organ damage and may prove fatal. The main objectives of the present survey were to screen these genetic variants and establish risk profiles for developing HH in Malays, Chinese and Indians. Methods: A total of two hundred and twenty-two unrelated and healthy individuals together representing Malay, Chinese and Indian ethnicities in Malaysia were scored for the H63D, S65C and C282Y variants using a polymerase chain reaction-restriction fragment length polymorphism technique. Results: There are clear differences in H63D, S65C and C282Y allele and genotype frequency distributions between Malays, Chinese and Indians. In particular, H63D is more common in Chinese (5.19%) and Indians (7.29%), while S65C is more common in Malays (1.03%) and Chinese (1.04%). In addition, a susceptibility genotype for HH (the compound heterozygote for C282Y and H63D) was only detected in Indians (0.02%). Conclusion: Overall, our study is the first to provide data on the prevalence of H63D, S65C, and C282Y genetic variants and HH risk profiles for Malays, Chinese and Indians.

Hipertransaminasemia, astenia, artralgias e hiperpigmentación cutánea / Hypertransaminasemia, asthenia, arthralgia and skin hyperpigmentation

RESUMEN La hemocromatosis hereditaria es una enfermedad metabólica infrecuente que afecta primariamente al hígado, y que se caracteriza por un incremento de la absorción intestinal de hierro. Se presentó un paciente de 49 años de edad, evaluado en consulta externa, desde alrededor de dos años atrás, por: astenia, anorexia, artralgias e hiperpigmentación cutánea, asociada a hipertransaminasemia y seronegatividad para virus B y C. Los niveles de saturación de transferrina y ferritina evidenciaron la sobrecarga de hierro, y el estado homocigoto para la mutación C282Y confirmó la sospecha diagnóstica; se descartaron otras condiciones como: hepatitis crónica por virus B y C, esteatohepatitis no alcohólica, anemia hemolítica crónica, anemia sideroblástica, talasemia mayor, u otras enfermedades metabólicas que afectan al hígado. La biopsia hepática mostró hallazgos típicos de esta condición. Las flebotomías semanales fueron bien toleradas y se logró una mejoría clínica del paciente y de los parámetros de laboratorio.

ABSTRACT Hereditary hemochromatosis is an uncommon metabolic disease, primarily affecting the liver in which increased intestinal absorption of iron is seen. We presented a 49- year -old patient who was evaluated in an outpatient clinic for suffering from asthenia, anorexia, arthralgia and skin hyperpigmentation associated with hypertransaminasemia and negative serology for B and C viruses from about two years ago. Serum ferritin, and transferrin saturation levels evidenced iron overload and homozygosity for the C282Y mutation confirmed the suspected diagnosis; other conditions were ruled out such as chronic hepatitis due to B and C viruses, non-alcoholic steatohepatitis, chronic hemolytic anemia, sideroblastic anemia, thalassemia major or some other metabolic diseases affecting the liver. Liver biopsy showed typical findings related to this condition. Weekly phlebotomies were well tolerated, as well as clinical improvement of the patient and laboratory parameters were achieved.

Trasplante Hepático: Supervivencia global del receptor en el Hospital de Especialidades Carlos Andrade Marín / Liver Transplantation: Overall survival at the Carlos Andrade Marín Specialty Hospital

INTRODUCCIÓN. El primer trasplante hepático en el mundo se realizó en Estados Unidos en 1963 por Thomas Starzl, hasta la década de los 90 la supervivencia al año fue de 73% y a los 5 años de 64%, según diferentes series que abarcaron más de 1 000 trasplantes realizados hasta 1989. El Ecuador requiere de estas estadísticas. El Hospital de Especialidades Carlos Andrade Marín inició la actividad del programa en mayo del 2016. OBJETIVO. Conocer la supervivencia global de los pacientes sometidos a trasplante hepático. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, con una población igual a la muestra de 62 datos de Historias Clínicas del Programa de Trasplante Hepático en la Unidad Técnica de Trasplante del Hospital de Especialidades Carlos Andrade Marín en el período mayo 2016 a diciembre 2019. Criterios de inclusión: pacientes so-metidos a trasplante hepático, con seguimiento durante 43 meses. La información se obtuvo de la base de datos del sistema AS400; se analizaron en el programa estadístico International Business Machines Statistical Package for the Social Sciences, versión 23.0. RESULTADOS. La supervi-vencia global a los 12 meses fue 72% (17; 62) y a los 43 meses fue 69% (19; 62). DISCUSIÓN. Se evidenció similares resultados descritos de supervivencia en centros con actividad en periodos cortos, menor a 5 años. CONCLUSIÓN. Se pudo conocer la supervivencia global de los pacientes trasplantados del hospital, cuya expectativa motiva a potenciar el programa para mejorar la calidad de vida de los pacientes candidatos a trasplante.

INTRODUCTION. The first liver transplant in the world was performed in the United States in 1963 by Thomas Starzl, until the 90s the survival at one year was 73% and at 5 years it was 64%, accor-ding to different series that included more than 1 000 transplants carried out until 1989. Ecuador re-quires these statistics. The Carlos Andrade Marín Specialty Hospital began program activity in May 2016. OBJECTIVE. To know the overall survival of patients undergoing liver transplantation. MATE-RIALS AND METHODS. Observational, descriptive study, with a population equal to the sample of 62 data from the Medical Records of the Liver Transplant Program in the Technical Transplant Unit of the Carlos Andrade Marín Specialty Hospital in the period May 2016 to December 2019. Inclusion criteria: patients submitted to liver transplantation, with follow-up for 43 months. The information was obtained from the AS400 system database; were analyzed in the statistical program Internatio-nal Business Machines Statistical Package for the Social Sciences, version 23.0. RESULTS. Ove-rall survival at 12 months was 72% (17; 62) and at 43 months it was 69% (19; 62). DISCUSSION. Similar survival results described were evidenced in centers with activity in short periods, less than 5 years. CONCLUSION. It was possible to know the overall survival of the transplanted patients at the hospital, whose expectation motivates us to promote the program to improve the quality of life of the transplant candidates.

Disseminated cryptococcosis and hemochromatosis: clues to diagnosis

Hepatic cirrhosis, diabetes mellitus and iron overload can each independently predispose to cryptococcosis. Hereditary hemochromatosis leads to all three of these predispositions. This report is the case of a patient with chronic hepatitis B virus infection and cirrhosis, who had markedly elevated serum ferritin and 99% transferrin saturation, and developed a leukemoid reaction. Autopsy revealed disseminated cryptococcosis for which the leukemoid reaction was a clue and possible hereditary hemochromatosis of which elevated ferritin and transferrin saturation can be clues. Hereditary hemochromatosis is an important diagnosis clinicians should never miss because early treatment with phlebotomy can be life-saving. Disseminated cryptococcosis can be rapidly diagnosed with serum cryptococcal antigen test and is treatable.

Ecografía Doppler strain 2D en la evaluación de la función ventricular en pacientes con diagnóstico reciente de hemocromatosis hereditaria / Two-dimensional Strain Echocardiography in the Evaluation of Ventricular Function in Patients with Newly Diagnosed Hereditary Hemochromatosis

RESUMEN Introducción: La hemocromatosis hereditaria es una enfermedad genética que genera una sobrecarga sistémica de hierro, y en etapas avanzadas, puede afectar el corazón. El compromiso miocárdico precoz por esta enfermedad no ha sido suficientemente investigado. Objetivo: Comparar mediante ecocardiografía Doppler convencional y strain 2D un grupo de pacientes con diagnóstico reciente de hemocromatosis hereditaria vs. un grupo control. Material y métodos: Se estudiaron pacientes con diagnóstico reciente de hemocromatosis hereditaria, no tratados. Se les realizó un ecocardiograma Doppler convencional y con strain bidimensional para evaluar la deformación longitudinal, radial y circunferencial, y el giro y torsión del ventrículo izquierdo. Resultados: Participaron 23 varones con hemocromatosis hereditaria (46 ± 18 años) y 20 sujetos control (45 ± 15 años). No hubo diferencias en los espesores y tamaños ventriculares. Los pacientes con hemocromatosis hereditaria tuvieron una fracción de eyección del ventrículo izquierdo menor (59 ± 4% vs. 62 ± 4 %; p = 0,01). No hubo diferencias en cuanto a ESPAM, TAPSE u onda s´ del ventrículo izquierdo. Se observó una disminución significativa del strain en los pacientes con HH, con mayor compromiso de la deformación radial (37 ± 12 % vs. 55 ± 17 %; p = 0,01) y circunferencial (−19,5 ± 2,8 % vs. −22,5 ± 2,8 %; p = 0,001), y, en menor medida, de la longitudinal (−19 ± 1,8 % vs. −21,1 ± 2,5 %; p=0,04). También este grupo tuvo menor rotación apical, menor giro (17,7 ± 13° vs. 25 ± 7°; p = 0,03) y menor torsión (2,3 ± 1,8 °/cm vs. 3,3 ± 1,1 °/cm; p = 0,03). No hubo correlación entre los diferentes tipos de deformación y los parámetros bioquímicos del metabolismo férrico. Conclusiones: La ecocardiografía y especialmente la evaluación del strain 2D es capaz de detectar de manera temprana ligeras alteraciones de la mecánica ventricular en pacientes asintomáticos, con sobrecarga sistémica de hierro por hemocromatosis hereditaria.

ABSTRACT Background: Hereditary hemochromatosis is a genetic disorder characterized by systemic iron overload which can involve the heart in advanced stages. Early myocardial involvement has not been thoroughly investigated. Objective: The aim of our study was to evaluate the performance of conventional Doppler-echocardiography and 2D strain echocardiography in a group of patients with newly diagnosed hereditary hemochromatosis vs. a control group. Methods: Patients with newly diagnosed hereditary hemochromatosis without treatment were included. All the patients underwent conventional Doppler echocardiography and 2D strain echocardiography with evaluation of left ventricular longitudinal, radial and circumferential strain, twist and torsion. Results: Twenty-three male patients with hereditary hemochromatosis (46±18 years) and 20 male controls (45±15 years) were included. There were no differences in ventricular dimensions and wall thickness. Left ventricular ejection fraction was lower in patients with hereditary hemochromatosis (59±4% vs. 62±4%; p=0.01). There were no differences in MAPSE, TAPSE and left ventricular s' velocity. There was a significant decrease in global strain in patients with hereditary hemochromatosis, with greater involvement of radial strain (37±12 % vs. 55±17%; p=0.01) and circumferential strain (-19.5±2.8% vs. -22.5±2.8%; p=0.001), and less involvement of longitudinal strain (-19±1.8% vs. -21.1±2.5%; p=0.04). Myocardial rotation showed lower twist (17.7±13° vs. 25±7°; p=0.03) and lower torsion (2.3±1.8°/cm vs. 3.3±1.1 °/cm; p=0.03). There was no correlation between the different strain parameters and iron metabolism. Conclusions: Echocardiography, and particularly 2D strain analysis can detect early abnormalities of ventricular mechanics in asymptomatic patients with systemic iron overload due to hereditary hemochromatosis.

Treatment of iron overload syndrome: a general review

SUMMARY INTRODUCTION Iron overload is a broad syndrome with a large spectrum of causative etiologies that lead to iron deposition. When iron exceeds defenses, it causes oxidative damage and tissular disfunction. Treatment may prevent organ dysfunction, leading to greater life expectancy. METHODS Literature from the last five years was reviewed through the use of the PubMed database in search of treatment strategies. DISCUSSION Different pharmacological and non-pharmacological strategies are available for the treatment of iron overload and must be used according to etiology and patient compliance. Therapeutic phlebotomy is the basis for the treatment of hereditary hemochromatosis. Transfusional overload patients and those who cannot tolerate phlebotomy need iron chelators. CONCLUSION Advances in the understanding of iron overload have lead to great advances in therapies and new pharmacological targets. Research has lead to better compliance with the use of oral chelators and less toxic drugs.

RESUMO INTRODUÇÃO A síndrome de sobrecarga de ferro engloba um grande espectro de etiologias que levam a um aumento da quantidade de ferro nos tecidos. Esse ferro excede a capacidade de proteção dos tecidos, levando a dano oxidativo e lesão tissular. Tratamento pode prevenir esse dano, levando à melhor sobrevida. METODOLOGIA A literatura dos últimos cinco anos foi revisada por meio de pesquisa na base de dados PubMed buscando identificar estratégias de tratamento. DISCUSSÃO Medidas farmacológicas e não farmacológicas estão disponíveis para o tratamento da síndrome de sobrecarga de ferro e devem ser utilizadas de acordo com a etiologia e a aceitação do paciente. A flebotomia terapêutica é base do tratamento dos pacientes com hemocromatose hereditária. Pacientes com sobrecarga transfusional ou aqueles que não toleram flebotomias devem utilizar quelantes de ferro. CONSIDERAÇÕES FINAIS Avanços no entendimento da síndrome de sobrecarga de ferro têm levado a grandes progressos na terapêutica, com promessas de abordagem de novos alvos farmacológicos. A evolução da pesquisa tem possibilitado melhor aderência com o uso de quelantes orais e com possibilidade de drogas menos tóxicas.

Hemocromatosis hereditaria: debut como cirrosis compensada de diagnóstico incidental. Reporte de un caso y revisión del tema / Hereditary hemochromatosis: debut as compensated cirrhosis of incidental diagnosis. Report of a case and review of the topic / Hemocromatose hereditária: estreia como cirrose compensada de diagnóstico incidental. Relatório de um caso e revisão do tópico

Resumen: La Hemocromatosis Hereditaria (HH) se define por la acumulación tisular de hierro, predominantemente en hígado, páncreas y miocardio, siendo una de las formas de sobrecarga férrica de causa congénita. El diagnóstico de HH en la edad adulta es poco frecuente en nuestro medio, y debe tenerse en cuenta ante hepatopatías crónicas de etiología incierta, más aún cuando se acompañan de elementos orientadores de afectación de otros tejidos. En este artículo se presenta el caso de un paciente alcoholista que debuta clínicamente con una hemorragia digestiva, contexto en el cual se establece el diagnóstico de cirrosis. Dados los antecedentes familiares de hepatopatía crónica de etiología incierta, el reciente diagnóstico de diabetes, y ante el hallazgo de un perfil de sobrecarga férrica, a pesar del consumo problemático de alcohol, se solicitaron los estudios destinados a confirmar el planteo de HH. El estudio genético en busca de homocigosis del alelo C282Y para el gen HFE resultó positivo. Se iniciaron flebotomías seriadas con buena evolución posterior. Se presenta el caso clínico y se realiza una revisión de la literatura.

Abstract: Hereditary Hemochromatosis (HH) is defined by tissue accumulation of iron, predominantly in theliver, pancreas and myocardium, being one of the forms of iron overload of congenital cause. The diagnosis of HH in adulthood is rare in our environment and must be taken into account in the presence of chronic liver disease of uncertain etiology. In this article we present a clinical case of an alcoholic patient who debuted clinically with a digestive bleeding, context in which the diagnosis of cirrhosis was established. Given the family history of chronic liver disease of uncertain etiology, the recent diagnosis of diabetes, and the finding of a profile of iron overload, despite problematic alcohol consumption, studies were requested to confirm the HH approach. The genetic study in search of homozygosis of the C282Y allele for the HFE gene was positive. Serial phlebotomies were started with favourable evolution at follow-up. The clinical case is presented, and a review of the literature is made.

Resumo: Hemocromatose hereditária (HH) por acumulação de ferro no tecido é definido predominantemente no fígado, no pâncreas e enfarte, uma das formas de sobrecarga de ferro causa congénita. Diagnóstico HH na idade adulta é raro em nossa área, e deve ser considerada a doença hepática crônica de etiologia desconhecida, mesmo quando acompanhadas por elementos de guia de envolvimento de outros tecidos. Este artigo apresenta o caso de um paciente com alcoolismo que estreou clinicamente com uma hemorragia digestiva, um contexto no qual o diagnóstico de cirrose é estabelecido. Dada a história familiar de doença hepática crônica de etiologia desconhecida, o diagnóstico recente de diabetes e antes da conclusão de um perfil de sobrecarga de ferro, apesar do uso problemático de álcool, estudos para confirmar a proposição de HH foram solicitados. O estudo genético em busca de homozigose do alelo C282Y para o gene HFE foi positivo. Flebotomias seriadas com boa evolução posterior foram iniciadas. O caso clínico é apresentado e uma revisão da literatura é feita.

Hemochromatosis International: therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr homozygous genotype / 中华肝脏病杂志

Hereditary hemochromatosis is a kind of hereditary metabolic liver disorders. It is caused by mutations in genes related to hemochromatosis, which leads to over deposition of iron in the liver, pancreas, skin, hypophysis, gonad and other organs and tissues of the whole body and is manifested as cirrhosis, diabetes, skin pigmentation, and low libido. Physicians of our country have inadequate understanding and familiarity with this disorder. Both the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases have issued guidelines for the diagnosis and treatment of hemochromatosis, but these two guidelines are complicated and difficult for Chinese clinical physician to comprehend. In 2018, Hepatology International published therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr homozygous genotype developed by Hemochromatosis International, these recommendations were objective, simple, and practical. We believe the above-mentioned guideline is understandable and helpful for clinicians and patients without medical education background. Therefore, herein the recommendations are translated into Chinese language, with a view to being able to be clinical work guide for the majority of Chinese hepatologists.

Characteristic findings of the liver iron overload on MRI and the feasibility of quantitative evaluation by IDEALGIQ / 实用放射学杂志

Objective To explore the classic MRI appearance of secondary hemochromatosis (SHC)related liver iron overload, and the feasibility of quantitative evaluation of liver iron overload by iterative decomposition of water and fat with echo asymmetry and leastGsquares estimationGiron quantification (IDEALGIQ).Methods 20 patients with SHCGrelated liver iron overload (experimental group)and 20 healthy adults (control group)underwent routine liver MRI and IDEALGIQ.The MRI images were comparatively analyzed to assess the hallmark of liver iron overload.In both two groups,the R2 ? values were measured on R2 ? maps,which were generated by IDEALGIQ,then the differences in age,gender and R2 ? value between two groups were comparatively analyzed.In experimental group,the serum ferritin (SF)was detected,and a correlation analysis was tested with R2 ? value.Results For all of the 20 patients, there was signal drop of liver parenchyma on T1 and T2 Gweighted images,signal loss with susceptibility artifact on DWI images,and signal dropped on inGphase images relative to outGofGphase images.Among the 20 patients,18 cases appeared "a dark liver parenchyma"on T2 G weighted images,and the spleen signal in 3 cases was similar to liver parenchyma’s hallmark.The R2 ? values in experimental group and control group were 395.58±255.75 Hz and 41.18±7.86 Hz (t＝－6.12,P＝0.00),respectively.No significant differences between two groups were found in gender and age (χ2＝0.10,P＝0.10 and t＝0.09,P＝0.93).The liver iron overload R2? value was not correlated with SF (r＝0.1 5 3 , P＝0.15).Conclusion On MRI,the typical appearance of liver iron overload is hypointense on T1 and T2Gweighted images,especially"a dark liver parenchyma"on T2 WI,signal drops on inGphase images relative to outGofGphase images,and signal loss with susceptibility artifact on DWI images.R2 ? value of IDEALGIQ can quantitatively evaluate the liver iron overload,without a correlation with SF.

Genetic diagnosis of hereditary hemochromatosis / 临床肝胆病杂志

Iron overload is not rarely seen in clinical practice, and hemochromatosis involving the liver is the most common type of iron overload. There is an extremely low incidence rate of the classic form of HFE hereditary hemochromatosis in the Asian population, which is different from the genetic background of the Caucasian population. European and American studies and international guidelines mainly focus on the HFE type, and there is low consistency between guidelines, with a lack of data from the Asian population. Therefore, with reference to the pathogenic genes of hereditary hemochromatosis and related data in China, this article discusses the genetic diagnosis of hereditary hemochromatosis, in order to provide a reference for the diagnosis and studies of hemochromatosis in the Chinese population.