ABSTRACT
Summary Objective: In liver diseases, hyperferritinemia (HYF) is related to injured cells in acquired and genetic conditions with or without iron overload. It is frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it is necessary to define the mean of HYF to establish the better approach for them. The present study evaluated the significance of elevated ferritin in patients with NAFLD and steatohepatitis (NASH). Method: The review was performed using search instruments of indexed scientific material, including MEDLINE (by PubMed), Web of Science, IBECS and LILACS, to identify articles published in Portuguese, English and Spanish, from 2005 to May, 2016. Studies eligible included place and year of publication, diagnose criteria to NAFLD, specifications of serum ferritin measurements and/or liver histopathologic study. Exclusion criteria included studies with patients with alcohol consumption ≥ 20 g/day and other liver diseases. Results: A total of 11 from 30 articles were selected. It included 3,564 patients and they were cross-sectional, retrospective, case series and case-control. The result's analyses showed in 10 of these studies a relationship between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis and insulin resistance. Conclusion: Hyperferritinemia in patients with NAFLD/NASH is associated more frequently with hepatocellular injury than hemochromatosis. These data suggest the relevance to evaluate carefully HYF in patients with NAFLD/NASH to establish appropriate clinical approach.
Resumo Objetivo: A hiperferritinemia (HPF) está associada à agressão hepatocelular nas doenças do fígado e à sobrecarga de ferro, em doenças genéticas e adquiridas. A HPF é frequente em pacientes com doença hepática gordurosa não alcoólica (DHGNA) e é necessário definir seu significado para estabelecer as melhores condutas para esses indivíduos. Esta revisão avaliou o significado da HPF em portadores de DHGNA e esteato-hepatite não alcoólica (EHNA). Método: A busca de artigos foi realizada através do PubMed (Medline), Web of Science e Lilacs, e foram selecionados aqueles publicados em português, inglês e espanhol de 2005 a maio de 2016. Os artigos foram elegíveis quando informavam data e local da publicação, critérios diagnósticos para DHGNA, especificações das dosagens de ferritina sérica e/ou estudo histopatológico. Foram excluídos os artigos cujos pacientes relataram ingestão alcoólica ≥ 20 g/dia ou eram portadores de outras doenças do fígado. Resultados: Foram selecionados 11 de 30 artigos, totalizando 3.564 pacientes. Os artigos eram de corte transversal, retrospectivos, série de casos e caso-controles. Em dez artigos, observou-se correlação entre alteração de ferritina e DHGNA/EHNA com e sem fibrose hepática e resistência à insulina. Conclusão: Hiperferritinemia em pacientes com DHGNA/EHNA se associa com maior frequência à agressão hepatocelular do que com sobrecarga de ferro hepático. Os resultados da revisão sugerem a necessidade de um maior cuidado na interpretação da elevação da ferritina sérica em pacientes com DHGNA/EHNA para o estabelecimento de condutas clínicas apropriadas.
Subject(s)
Humans , Iron Overload/etiology , Iron Overload/blood , Ferritins/blood , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/blood , Risk Factors , Iron Overload/pathology , Non-alcoholic Fatty Liver Disease/pathology , Iron/bloodABSTRACT
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.
Subject(s)
Humans , Male , Female , Middle Aged , Oxidative Stress/genetics , Iron Overload/genetics , Non-alcoholic Fatty Liver Disease/genetics , Inflammation/genetics , Iron/analysis , Liver/chemistry , Serine Endopeptidases/genetics , Gene Expression Regulation , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/blood , Inflammation Mediators/blood , Iron Overload/diagnosis , Iron Overload/blood , STAT3 Transcription Factor/genetics , Interleukin-1beta/genetics , Interleukin-1beta/blood , Real-Time Polymerase Chain Reaction , Hepcidins/genetics , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/blood , Inflammation/diagnosis , Inflammation/blood , Liver/pathology , Membrane Proteins/geneticsABSTRACT
La sobrecarga de hierro es una complicación frecuente en un número importante de enfermedades hematológicas que cursan con anemia y requieren transfusiones sanguíneas como parte de su terapia. Entre ellas se destacan la talasemia, la drepanocitosis, los síndromes mielodisplásicos, la anemia de Blackfan-Diamond, la anemia de Fanconi y la deficiencia de piruvato quinasa, La sobrecarga de hieroo tambiún se presenta en otras enfermedades tales como la hemocromatosis hereditaria, la hepatitis viral, el síndrome metabólico y determinados trastornos neurovegetativos. El diagnóstico de sobrecarga suele hacerse mediante la determinación del hierro sérico no unido a la transferrina, la ferritina sérica y un aumento de la concentración hepática de hierro. Las consecuencias más importantes del efecto tóxico de un exceso de hierro son las disfunciones cardíacas y endocrinas, debidas al efecto oxidante del hierro sobre las membranas celulares, con el consiguiente daño celular. Tales alteraciones contribuyen al incremento de la morbilidad y la mortalidad en estos pacientes. El tratamiento consiste básicamente en el usode agentes quelantes de hierro que facilitan la excreción del exceso del metal y reducen su efecto tóxico, Entre tales agentes se cuentan la deferrioxamina (de uso intravenoso). y móa recientemente el deferiprone (ambos de uso orak)
Iron overload is a frequent complication in patients with hematological diseases which develop anemía and require blood transfusion as a therapeutic measure. Thalassemia, drepanocytosis, myelodisplastic syndromes, Blackfan-Diamond anemia, Franconi anemia and pyruvate kinase deficiency are the most common of these diseases. Iron overload is the hallmark of hereditary hemochromatosis, and also complicates diseases such as viral hepatitis, the metabolic syndrome, and certain neurovegetative disfunctions. The diagnosis of iron overload is commonly established through the evaluation of serum iron, transferrin saturation, serum ferritin and liver iron concentration. Cardiac and endocrine dysfunctions are the most important consequences of the toxic efffect of iron accumulation; these are due to the oxidixing effect of iron upon the cellular membranes, followed by cellular damage. Such alterations contribute to the increased morbility and mortality rates in these patients. The treatment of iron overload is based mainly on the use of iron chelators which facilitate the excretion of iron excess and reduce its toxic effect. Deferrioxamine (for intravenous use), and more recently deferiprone and deferasirox (both for oral administration) are the drugs of choice
Subject(s)
Humans , Male , Female , Anemia/genetics , Hematologic Diseases/complications , Iron Overload/pathology , Iron Overload/blood , Hemochromatosis/etiology , Thalassemia/etiology , Blood Transfusion/methodsABSTRACT
Se modificó la técnica de Perls para disponer de un medio que pudiera revelar la presencia del pigmento férrico y poder utilizarlo en el diagnóstico histopatológico; para ello se elevó a 58 grados centígrados la temperatura en los reactivos, lo cual no se hace en el procedimiento habitual, y el citado pigmento se tiñó de verde o azul, de manera que fue posible identificarlo en los núcleos grises de la base en un paciente con síndrome de Hallervordem - Spatz, que falleció en esta institución.
The technique of Perls was modified to have a mean that could reveal the presence of the ferric pigment and to be able to use it in the histopathological diagnosis; for this purpose the temperature was rised to 58º centigrades in the reagents, which is not done in the habitual procedure, and the mentioned pigment was stained of green or blue, so that it was possible to identify it in the gray nuclei of the base in a patient with syndrome of Hallervordem - Spatz, who died in this institution.
Subject(s)
Humans , Male , Adolescent , Diagnostic Techniques and Procedures , Pathology Department, Hospital , Iron Overload/diagnosis , Iron Overload/blood , Iron Metabolism Disorders/diagnosis , Iron Metabolism Disorders/bloodABSTRACT
INTRODUCTION: Short stature is common in thalassaemia major. Hypothyroidism resulting from haemosiderosis has been implicated, but this complication has not been investigated in Sri Lanka. OBJECTIVES: To estimate the thyroid hormone level of patients with thalassaemia major and correlate height with age, iron status and thyroid hormone level. SETTING: University Unit, Lady Ridgeway Hospital, Colombo. DESIGN: A cross-sectional comparative study. METHODS: 33 patients with thalassemia major (19 males) aged 2 years 6 months to 23 years were studied. 21 healthy age and sex matched subjects from the same neighbourhood as the patients served as controls. Anthropometric measurements, skeletal maturity, serum ferritin and thyroid hormone levels were estimated. RESULTS: The height centiles and height standard deviation scores (SDS) were significantly lower in the patient group. Skeletal maturation was delayed by more than 1 year in 69% of patients. Undernutrition was not seen. The height SDS showed significant reduction with age (r = -0.5, 95% confidence limit -0.72 to -0.18) and with elevated serum ferritin levels (r = -0.8, 95% confidence limit = -0.9 to 0.62). Serum ferritin levels were elevated in the entire patient group with 70% being heavily iron overloaded (serum ferritin > 7000 ng/ml). The thyroxine (T4) levels were within the normal range in all 33 patients. The TSH levels were normal in 32 patients. The patient too had a normal T4 level. The control group had TSH levels comparable with the patients. CONCLUSION: Hypothyroidism was not present in our iron overloaded thalassaemic patients. The thyroid hormone levels were similar in patients with mild and heavy iron overload. We conclude that routine surveillance for hypothyroidism is unnecessary in thalassaemia major. Other causes for delayed skeletal maturation and short stature need investigation.