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1.
Medicine (Baltimore) ; 103(19): e38104, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728445

ABSTRACT

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which is mainly characterized by joint swelling, pressure pain and joint destruction. Some patients may suffer from a variety of serious complications, which require prompt diagnosis and treatment. Otherwise, the patient condition may deteriorate rapidly, leading to premature death. OBJECTIVE: We reported a case of RA combined with hyperferritinemic syndrome and capillary leak syndrome (CLS) that was successfully treated with tocilizumab (TCZ), with the aim of improving diagnostic ideas for clinicians and consequently improving the diagnosis and treatment of the hyperferritinemic syndrome and CLS. CASE SUMMARY: A 55-year-old female patient was admitted to the Department of Infectious Diseases of our hospital due to "recurrent fever for more than 1 month and aggravation for 3 days." The patient was diagnosed with fever of unknown origin (lung infection?) and received anti-infective therapy with large encirclement of anti-bacterial, antifungal and empirical anti-tuberculosis successively during hospitalization in the Department of Infectious Diseases. Yet her condition continues to progress. The patient was eventually diagnosed with RA combined with hyperferritinemic syndrome and CLS. Then she received glucocorticoids (GC) (160 mg qd) combined with intravenous immunoglobulin (IVIG, 20 g/d, for 3 days). We considered that the patient also had an overwhelming proinflammatory cytokine storm, so she received a strong anti-inflammatory treatment with TCZ (400 mg qm). The patient symptoms and follow-up chest CT showed significant improvement following treatment. CONCLUSION: TCZ has good efficacy in the treatment of RA combined with hyperferritinemic syndrome and CLS and is expected to be a promising treatment.


Subject(s)
Antibodies, Monoclonal, Humanized , Arthritis, Rheumatoid , Capillary Leak Syndrome , Hyperferritinemia , Humans , Female , Middle Aged , Hyperferritinemia/drug therapy , Hyperferritinemia/etiology , Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/complications , Capillary Leak Syndrome/drug therapy , Capillary Leak Syndrome/etiology , Syndrome
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 284-292, 2024 Apr 18.
Article in Chinese | MEDLINE | ID: mdl-38595246

ABSTRACT

OBJECTIVE: To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies (IIMs) patients receiving conventional treatment. METHODS: Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were included. The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics, laboratory features, peripheral blood lymphocytes, immunological indicators, and therapeutic drugs. RESULTS: Among the 635 patients included, 518 patients finished the follow-up, with an average time of 36.8 months. The total complete clinical response rate of IIMs was 50.0% (259/518). The complete clinical response rate of dermatomyositis (DM), anti-synthetase syndrome (ASS) and immune-mediated necrotizing myopathy (IMNM) were 53.5%, 48.9% and 39.0%, respectively. Fever (P=0.002) and rapid progressive interstitial lung disease (RP-ILD) (P=0.014) were observed much more frequently in non-complete clinical response group than in complete clinical response group. The aspartate transaminase (AST), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group. As for the treatment, the percentage of glucocorticoid received and intravenous immunoglobin (IVIG) were significantly higher in non-complete clinical response group than in complete clinical response group. Risk factor analysis showed that IMNM subtype (P=0.007), interstitial lung disease (ILD) (P=0.001), eleva-ted AST (P=0.012), elevated serum ferritin (P=0.016) and decreased count of CD4+T cells in peripheral blood (P=0.004) might be the risk factors for IIMs non-complete clinical response. CONCLUSION: The total complete clinical response rate of IIMs is low, especially for IMNM subtype. More effective intervention should be administered to patients with ILD, elevated AST, elevated serum ferritin or decreased count of CD4+T cells at disease onset.


Subject(s)
Autoimmune Diseases , Hyperferritinemia , Lung Diseases, Interstitial , Myositis , Humans , Autoantibodies , Myositis/diagnosis , Pathologic Complete Response , Retrospective Studies
3.
Sci Rep ; 14(1): 5899, 2024 03 11.
Article in English | MEDLINE | ID: mdl-38467670

ABSTRACT

SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.


Subject(s)
COVID-19 , Hyperferritinemia , Pneumonia, Viral , Child , Humans , SARS-CoV-2 , COVID-19/diagnostic imaging , Point-of-Care Systems , Retrospective Studies , Pneumonia, Viral/diagnostic imaging , Lung/diagnostic imaging , Hospitalization , Transaminases
4.
Scand J Gastroenterol ; 59(5): 592-599, 2024 May.
Article in English | MEDLINE | ID: mdl-38329447

ABSTRACT

BACKGROUND & AIMS: Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene. METHODS: The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m2). The effects of HFE variants on these associations were also evaluated. RESULTS: Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes (n = 92) and severe liver-related outcomes (n = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02-1.21]; p = 0.012 and HR 1.11 [95% CI 1.02-1.21]; p = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes. CONCLUSION: Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia.


Subject(s)
Ferritins , Genotype , Hemochromatosis Protein , Liver Cirrhosis , Humans , Male , Liver Cirrhosis/blood , Liver Cirrhosis/genetics , Middle Aged , Ferritins/blood , Hemochromatosis Protein/genetics , Female , Adult , Finland/epidemiology , Aged , Proportional Hazards Models , Linear Models , Hyperferritinemia/blood , Hyperferritinemia/genetics , Risk Factors
5.
Ceska Slov Farm ; 73(1): 223-232, 2024.
Article in English | MEDLINE | ID: mdl-38185645

ABSTRACT

Worldwide, hundreds of millions of people have been infected with COVID-19 since December 2019; however, about 20% or less developed severe symptoms. The main aim of the current study was to  assess  the  relationship  between  the  severity of Covid-19 and different clinical and laboratory parameters. A total number of 466 Arabs have willingly joined this prospective cohort. Out of the total number, 297 subjects (63.7%) had negative COVID-19 tests, and thus, they were recruited as controls, while 169 subjects (36.3%) who tested positive for COVID-19 were enrolled as cases. Out of the total number of COVID-19 patients, 127 (75.15%) presented with mild symptoms, and 42 (24.85%) had severe symptoms. The age range for the participants was 20 to 82 years. Compared with controls, the severity of the disease was associated with significantly high ferritin levels (P < 0.001). The severity of the disease was also associated with a significant increase in C-reactive protein (P < 0.001), D-dimer (P < 0.001), white blood cell count (WBC) (P < 0.01), IgM (P < 0.001), and Granulocytes (P < 0.01). In addition, severe COVID-19 symptoms in the current study were associated with a significant decrease in lymphocytes (P < 0.01). There was a four-fold increase in serum ferritin levels in COVID-19 patients presented with severe symptoms upon admission. The former was associated with significantly high levels of CRP and D-dimer. Thus, hyperferritinemia, together with high CRP and D-dimer concentrations, may serve as reliable predictors for disease severity and poor prognosis in Arabs with COVID-19.


Subject(s)
COVID-19 , Hyperferritinemia , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Prospective Studies , Ferritins , Prognosis
6.
Pediatr Neurol ; 152: 162-168, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38295717

ABSTRACT

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a fulminant disease with poor prognosis. Cytokine storm is the important phenomenon of ANE that affects the brain and multiple organs. The study aimed to identify whether hyperferritinemia was associated with poor prognosis in patients with ANE. METHODS: All patients with ANE had multiple symmetric lesions located in the bilateral thalami and other regions such as brainstem tegmentum, cerebral white matter, and cerebellum. Neurological outcome at discharge was evaluated by pediatric neurologists using the Pediatric Cerebral Performance Category Scale. All risk factors associated with poor prognosis were further analyzed using receiver operating characteristic curve analysis. RESULTS: Twenty-nine patients with ANE were enrolled in the current study. Nine (31%) patients achieved a favorable neurological outcome, and 20 (69%) patients had poor neurological outcomes. results The group of poor neurological outcome had significantly higher proportion of shock on admission and brainstem involvement. Based on multivariate logistic regression analysis, ferritin, aspartate aminotransferase (AST), and ANE severity score (ANE-SS) were the predictors associated with outcomes. The appropriate cutoff value for predicting neurological outcomes in patients with ANE was 1823 ng/mL for ferritin, 78 U/L for AST, and 4.5 for ANE-SS. Besides, comparison analyses showed that higher level of ferritin and ANE-SS were significantly correlated with brainstem involvement (P < 0.05). CONCLUSIONS: Ferritin may potentially be a prognostic factor in patients with ANE. Hyperferritinemia is associated with poor neurological outcomes in patients with ANE and ferritin levels more than 1823 ng/mL have about eightfold increased risk of poor neurological outcome.


Subject(s)
Brain Diseases , Hyperferritinemia , Leukoencephalitis, Acute Hemorrhagic , Child , Humans , Leukoencephalitis, Acute Hemorrhagic/etiology , Ferritins , Hyperferritinemia/complications , Magnetic Resonance Imaging/methods , Brain Diseases/complications
7.
J Clin Endocrinol Metab ; 109(6): 1540-1549, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38124275

ABSTRACT

CONTEXT: There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. OBJECTIVE: We aimed to validate the clinical outcomes of MHF in the general population and patients with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: The NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males]-550 ng/mL; grade 2: 550-1000 ng/mL; grade 3: >1000 ng/mL). The clinical outcomes, including all-cause death, comorbidities, and liver histology, were compared between non-MHF and MHF in adjusted models. RESULTS: In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (P = .036), elevated albumin-creatinine ratio (UACR, P = .001), and sarcopenia (P = .013). Although the association between all grades of MHF and mortality was insignificant (P = .122), grades 2/3 was associated with increased mortality (P = .029). When comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P < .001), elevated UACR (P < .001), cardiovascular disease (P = .028), and sarcopenia (P < .001). In the PERSONS cohort, MHF was associated with more advanced grades of steatosis (P < .001), lobular inflammation (P < .001), advanced fibrosis (P = .017), and more severe hepatocellular iron deposition (P < .001). CONCLUSION: Both in the general population and in at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes.


Subject(s)
Ferritins , Hyperferritinemia , Humans , Female , Male , Middle Aged , Adult , Cohort Studies , Hyperferritinemia/blood , Hyperferritinemia/diagnosis , Ferritins/blood , Consensus , Nutrition Surveys , Aged , Prognosis
8.
Rinsho Ketsueki ; 64(11): 1410-1414, 2023.
Article in Japanese | MEDLINE | ID: mdl-38072426

ABSTRACT

An asymptomatic woman in her early 40s with a history of hyperferritinemia (5,412 ng/ml) was referred to our hospital after repeated phlebotomy for hemosiderosis. She had unexplained hyperferritinemia, low-normal transferrin saturation, and high hepcidin levels, in the absence of iron overload-induced organ injury. She was diagnosed with ferroportin disease based on detection of the SLC40A1 variant SLC40A1 c.485_487del (p.Val162del) on genetic analysis. Her ferritin levels remained stable during pregnancy, and postpartum anemia was successfully treated with 2-week oral iron therapy. Ferroportin disease is characterized by impaired iron export and preferential iron trapping in tissue macrophages. To reduce risk of anemia, a non-aggressive phlebotomy regimen is recommended in patients with ferroportin disease, which shows a milder clinical course compared with other classical hemochromatosis subtypes.


Subject(s)
Anemia , Hemochromatosis , Hyperferritinemia , Iron Overload , Humans , Female , Pregnancy , Hemochromatosis/therapy , Hemochromatosis/diagnosis , Hemochromatosis/genetics , Iron Overload/etiology , Iron , Hepcidins
9.
Clin Res Hepatol Gastroenterol ; 47(10): 102224, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37813276

ABSTRACT

BACKGROUND: Hyperferritinemia is found in around 12 % of the general population. Analyzing the cause can be difficult. In case of doubt about the presence of major iron overload most guidelines advice to perform a MRI as a reliable non-invasive marker to measure liver iron concentration (LIC). In general, a LIC of ≥ 36 µmol/g dw is considered the be elevated however in hyperferritinemia associated with, for example, obesity or alcohol (over)consumption the LIC can be ≥ 36 µmol/g dw in abscence of major iron overload. So, unfortunately a clear cut-off value to differentiate iron overload from normal iron content is lacking. Previously the liver iron index (LII) (LIC measured in liver biopsy (LIC-b)/age (years)), was introduced to differentiate between patients with major (LII ≥ 2) and minor or no iron overload (LII < 2). Based on the good correlation between the LIC-b and LIC determined with MRI (LIC-MRI), our goal was to investigate whether a LII_MRI ≥ 2 is a good indicator of major iron overload, reflected by a significantly higher amount of iron needed to be mobilized to reach iron depletion. METHODS: We compared the amount of mobilized iron to reach depletion and inflammation-related characteristics in two groups: LII-MRI ≥ 2 versus LII-MRI <2 in 92 hyperferritinemia patients who underwent HFE genotyping and MRI-LIC determination. RESULTS: Significantly more iron needed to be mobilized to reach iron depletion in the LII ≥ 2 group (mean 4741, SD ± 4135 mg) versus the LII-MRI <2 group (mean 1340, SD ± 533 mg), P < 0.001. Furthermore, hyperferritinemia in LII-MRI < 2 patients was more often related to components of the metabolic syndrome while hyperferritinemia in LII-MRI ≥ 2 patients was more often related to HFE mutations. ROC curve analysis showed good performance of LII =2 as cut-off value. However the calculations showed that the optimal cut-off for the LII = 3.4. CONCLUSION: The LII-MRI with a cut-off value of 2 is an effective method to differentiate major from minor iron overload in patients with hyperferritinemia. But the LII-MRI = 3.4 seems a more promising diagnostic test for major iron overload.


Subject(s)
Hyperferritinemia , Iron Overload , Humans , Iron/analysis , Iron/metabolism , Hyperferritinemia/complications , Hyperferritinemia/metabolism , Hyperferritinemia/pathology , Liver/metabolism , Iron Overload/diagnostic imaging , Iron Overload/etiology , Magnetic Resonance Imaging
10.
Inn Med (Heidelb) ; 64(10): 955-960, 2023 Oct.
Article in German | MEDLINE | ID: mdl-37702780

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterized by hyperferritinemia. A differentiation is made between hereditary and acquired forms. In contrast to children, almost all cases in adult patients consist of acquired secondary HLH. Infections, malignancies and autoimmune diseases are frequent triggers of secondary HLH. More recently, cases of HLH have also been described in association with immunotherapy, e.g., when using chimeric antigen receptor (CAR) T­cell treatment. In critically ill patients in the intensive care unit (ICU), sepsis represents the major differential diagnosis of HLH due to the frequently similar clinical presentation. Sometimes both sepsis and HLH are present at the same time. An early diagnosis and timely initiation of immunosuppressive treatment are essential for the further course and prognosis of HLH. Therefore, HLH should be considered as a possible diagnosis in critically ill patients with persistent fever and additional compatible symptoms (e.g., splenomegaly, neurological symptoms) or laboratory parameters (e.g., hyperferritinemia, cytopenia of two or three cell lines, increased transaminases). The diagnosis of HLH is made on the basis of the HLH-2004 criteria. The HScore can be used to estimate the probability of the presence of HLH. Corticosteroids given at high doses are the cornerstone of HLH treatment. Furthermore, immunoglobulins, etoposide, anakinra or ruxolitinib can complement treatment depending on the HLH trigger. The course of HLH depends on the timely initiation of treatment, the underlying trigger and the response to treatment. Despite progress in terms of diagnostics and targeted treatment, the prognosis of critically ill HLH patients is still poor.


Subject(s)
Hyperferritinemia , Lymphohistiocytosis, Hemophagocytic , Adult , Child , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Critical Illness , Immunotherapy , Intensive Care Units
11.
Nutrition ; 116: 112190, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37734118

ABSTRACT

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is related to obesity, insulin resistance, dyslipidemia, and metabolic syndrome. The increasing prevalence of NAFLD results in a significant number of patients manifesting chronic liver disease over time. The aim of this study was to analyze the predictive factors to estimate NAFLD severity in patients who are candidates for Roux-en-Y gastric bypass. METHODS: This descriptive observational study was conducted with 136 obese patients who were candidates for Roux-en-Y gastric bypass and had mild, moderate, or severe NAFLD. RESULTS: Severe NAFLD was more prevalent among the men (P = 0.007), and mild NAFLD was more prevalent among the women (P = 0.007). Hyperferritinemia was observed in the group with severe NAFLD (P = 0.01). Neck circumference and waist-to-height ratio were associated with an increased risk when comparing the groups with mild and severe NAFLD and those with moderate and severe NAFLD (P = 0.023 and P = 0.001, respectively); the alanine aminotransferase (ALT) and aspartate aminotransferase ratio values were >1 (P = 0.002) in the same comparisons. The regression analyses showed that an increase of 1 ng/mL in vitamin D reduced the chances of severe steatosis by 10% (P = 0.043), and an increase of 1 U/L ALT increased the chances of severe steatosis by 13% (P = 0.002). CONCLUSION: High neck circumference and low waist-to-height ratio values, male sex, hyperferritinemia, increased serum ALT values, and decreased vitamin D levels were related to the risk for severe NAFLD.


Subject(s)
Gastric Bypass , Hyperferritinemia , Non-alcoholic Fatty Liver Disease , Humans , Male , Female , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/etiology , Hyperferritinemia/complications , Obesity/complications , Vitamin D , Alanine Transaminase
12.
Crit Care ; 27(1): 347, 2023 09 06.
Article in English | MEDLINE | ID: mdl-37674218

ABSTRACT

BACKGROUND: One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis. METHODS: We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed. RESULTS: Mortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55-9.60]; z = 4.728; P-value < 0.0001). Hyperferritinemic sepsis had higher C-reactive protein, sCD163, IL-22, IL-18, IL-18 binding protein, MIG/CXCL9, IL-1ß, IL-6, IL-8, IL-10, IL-17a, IFN-γ, IP10/CXCL10, MCP-1/CCL2, MIP-1α, MIP-1ß, TNF, MCP-3, IL-2RA (sCD25), IL-16, M-CSF, and SCF levels; lower ADAMTS13 activity, sFasL, whole blood ex vivo TNF response to endotoxin, and TRAIL levels; more Adenovirus, BK virus, and multiple virus DNAemias; and more MAS (P-value < 0.05). Among these variables, only MCP-1/CCL2 (the monocyte chemoattractant protein), MAS, and ferritin levels were directly causally associated with mortality. MCP-1/CCL2 and hyperferritinemia showed direct causal association with depressed ex vivo whole blood TNF response to endotoxin. MCP-1/CCL2 was a mediator of MAS. MCP-1/CCL2 and MAS were mediators of hyperferritinemia. CONCLUSIONS: These findings establish hyperferritinemic sepsis as a high-risk condition characterized by increased cytokinemia, viral DNAemia, thrombotic microangiopathy, immune depression, macrophage activation syndrome, and death. The causal analysis provides rationale for designing anti-inflammatory trials that reduce macrophage activation to improve survival and enhance infection clearance in pediatric hyperferritinemic sepsis.


Subject(s)
Hyperferritinemia , Macrophage Activation Syndrome , Sepsis , Humans , Child , Macrophage Activation Syndrome/complications , Sepsis/complications , Cytokines , Ferritins
13.
Int J Mol Sci ; 24(15)2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37569253

ABSTRACT

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis-a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.


Subject(s)
Cataract , Hyperferritinemia , Iron Metabolism Disorders , Humans , Brazil , Pedigree , Iron Metabolism Disorders/pathology , Cataract/pathology , Mutation
14.
Am J Hum Genet ; 110(8): 1436-1443, 2023 08 03.
Article in English | MEDLINE | ID: mdl-37490907

ABSTRACT

Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. We previously studied eleven healthy subjects from eight different families presenting with unexplained hyperferritinemia. Their findings suggested the existence of an autosomal-recessive disorder. We carried out whole-exome sequencing to detect the genetic cause of hyperferritinemia. Immunohistochemistry and flow cytometry assays were performed on liver biopsies and monocyte-macrophages to confirm the pathogenic role of the identified candidate variants. Through a combined approach of whole-exome sequencing and homozygosity mapping, we found bi-allelic STAB1 variants in ten subjects from seven families. STAB1 encodes the multifunctional scavenger receptor stabilin-1. Immunohistochemistry and flow cytometry analyses showed absent or markedly reduced stabilin-1 in liver samples, monocytes, and monocyte-derived macrophages. Our findings show a strong association between otherwise unexplained hyperferritinemia and bi-allelic STAB1 mutations suggesting the existence of another genetic cause of hyperferritinemia without iron overload and an unexpected function of stabilin-1 in ferritin metabolism.


Subject(s)
Hyperferritinemia , Iron Overload , Humans , Iron Overload/genetics , Iron Overload/diagnosis , Ferritins/genetics , Macrophages , Alleles
15.
Rev Med Interne ; 44(12): 656-661, 2023 Dec.
Article in French | MEDLINE | ID: mdl-37507250

ABSTRACT

Etiological investigation of hyperferritinemia includes a full clinical examination, with the measurement of waist circumference, and simple biological tests including transferrin saturation. The classification between hyperferritinemia without iron overload (inflammation, excessive alcohol intake, cytolysis, L-ferritin mutation) or with iron overload is then relatively easy. Dysmetabolic iron overload syndrome is the most common iron overload disease and is defined by an unexplained serum ferritin level elevation associated with various metabolic syndrome criteria and mild hepatic iron content increase assessed by magnetic resonance imaging. Bloodlettings are often poorly tolerated without clear benefit. Type 1 genetic hemochromatosis (homozygous C282Y mutation on the HFE gene) leads to iron accumulation through an increase of dietary iron absorption due to hypohepcidinemia. More than 95% of hemochromatosis are type 1 hemochromatosis but the phenotypic expression is highly variable. Elastography is recommended to identify advanced hepatic fibrosis when serum ferritin exceeds 1000µg/L. Life expectancy is normal when bloodlettings are started early. Ferroportin gene mutation is an autosomal dominant disease with generally moderate iron overload. Chelators are used in iron overload associated with anaemia (myelodysplastic syndromes or transfusion-dependent thalassemia). Chelation is initiated when hepatic iron content exceeds 120µmol/g. Deferasirox is often used as first-line therapy, but deferiprone may be of interest despite haematological toxicity (neutropenia). Deferoxamine (parenteral route) is the treatment of choice for severe iron overload or emergency conditions.


Subject(s)
Hemochromatosis , Hyperferritinemia , Iron Overload , Humans , Hemochromatosis/diagnosis , Hemochromatosis/genetics , Hemochromatosis/therapy , Hyperferritinemia/complications , Iron Overload/diagnosis , Iron Overload/etiology , Iron Overload/therapy , Iron/metabolism , Ferritins
16.
Acta Gastroenterol Belg ; 86(2): 356-359, 2023.
Article in English | MEDLINE | ID: mdl-37428170

ABSTRACT

Hyperferritinemia is a common reason for referral to a hepatogastroenterologist. The most frequent causes are not associated with iron overload (e.g. inflammatory diseases, alcohol abuse, metabolic syndrome, etc.). However, hyperferritinemia can also be caused by a genetic variant in one of the iron regulatory genes, called hereditary hemochromatosis, often but not always associated with iron overload. A variation in the human Hemostatic Iron Regulator protein (HFE) gene is the most common genotype, but many other variants have been described. In this paper we discuss two cases of rare hyperferritinemia associated disorders, ferroportin disease and hyperferritinemia-cataract syndrome. We also propose an algorithm for evaluating hyperferritinemia, facilitating a correct diagnosis and preventing potentially unnecessary examinations and therapeutic actions.


Subject(s)
Hemochromatosis , Hyperferritinemia , Iron Overload , Humans , Hemochromatosis/diagnosis , Hemochromatosis/genetics , Diagnosis, Differential , Mutation , Iron Overload/genetics , Iron/metabolism , Genes, Regulator
17.
Georgian Med News ; (337): 110-117, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37354683

ABSTRACT

SARS-CoV-2 can cause sepsis regardless of the presence of secondary bacterial or fungal infections. The virus itself likely causes sepsis through a variety of possible mechanisms, including immune dysregulation, with respiratory dysfunction, which as a result of circulatory dysfunction leads to hypoxemia and metabolic acidosis. We conducted cohort study, comparing outcomes of 212 critically ill patients with Septic shock (134 men (63.3%) and 78 women (36.7%), with a mean age between 40-70 years) were evaluated, who were treated in the intensive care unit of First University Clinic during 2020-2021 years. All four groups had documented Hyperferritinemia (HF). Patients were divided according to ferritin concentrations: moderate HF (ferritin <1500ng/ml) and severe HF (ferritin >1500ng/ml). The study aimed to reveal the impact of the Angiotensin-Converting enzyme -2 (ACE2) inhibitors on the course of the Septic shock developed during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF). Study results show that severe HF in patients with Septic shock is associated with a high risk of mortality and can be considered an indicator of the severity of the disease. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock: ACE2 inhibitors reduce the levels of Ang II and C reactive protein (CRP) in the blood in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate and severe HF; regulate the activity of leukocytes and the blood pro-coagulation system in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate HF; reduce the expression of pro-inflammatory cytokines (IL-6), decrease the level of D dimer in СOVID-infected patients in conditions of moderate HF; Procalcitonin levels do not differ between COVID-19 infected and non-infected patients with Septic shock. Based on our study, we can assume that there is the important link between elevated Ang 2 and the quality of immunological disorders and inflammation. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock.


Subject(s)
COVID-19 , Hyperferritinemia , Sepsis , Shock, Septic , Male , Humans , Female , Adult , Middle Aged , Aged , COVID-19/complications , Shock, Septic/complications , Shock, Septic/drug therapy , Angiotensin-Converting Enzyme Inhibitors , SARS-CoV-2 , Cohort Studies , Angiotensin-Converting Enzyme 2 , Angiotensins
18.
Pediatr Crit Care Med ; 24(9): e409-e416, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37125796

ABSTRACT

OBJECTIVES: Hyperferritinemia in the critical phase of dengue infections may correlate with severe dengue ( sd ) disease, and our primary objective was to examine the association between ferritin level on day 1 of PICU admission and 2009 World Health Organization (WHO) criteria for sd . Our secondary objective was outcome in relation to care. It is unclear whether immunomodulatory therapy during the critical phase may restore immune homeostasis and mitigate disease severity. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of children with dengue 1 month to 16 years old with admission ferritin greater than or equal to 500 ng/mL requiring PICU admission. Demographics, clinical, and laboratory parameters, presence of the 2009 WHO sd criteria and outcomes were analyzed. Immunomodulatory therapy was used when there was persistent hyperinflammation beyond the critical phase of plasma leakage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-five patients were admitted in the critical phase of dengue with median (interquartile range) ferritin levels of 8,105 ng/mL (2,350-15,765 ng/mL). Patients with at least one WHO sd category had higher ferritin levels compared to those without any sd criteria, with the highest levels in eight patients with all three sd categories. In our cohort of 55, 52 patients (94%) recovered with standard supportive therapy. Recovery was associated with decreased ferritin levels that occurred in parallel with improved circulation and platelet counts; this included 22 of 24 patients with admission ferritin levels greater than or equal to 10,000 ng/mL and two with ferritin greater than 1,00,000 ng/mL. Immunomodulation was used in three patients with unremitting fever, persistent hyperferritinemia, and progressive multiple organ dysfunction beyond the critical phase, of whom two died. CONCLUSIONS: Hyperferritinemia in the critical phase of sd is associated with the number of 2009 WHO sd criteria present. Our data also indicate that many patients with sd recover well with supportive care.


Subject(s)
Hyperferritinemia , Severe Dengue , Child , Humans , Retrospective Studies , Ferritins , Platelet Count
19.
Hormones (Athens) ; 22(3): 403-412, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37233914

ABSTRACT

PURPOSE: To investigate the relationship between the triglyceride-glucose (TyG) index and serum ferritin (SF) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 881 T2DM patients were divided into T1(TyG index < 1.66), T2 (1.66 ≤ TyG index < 2.21), and T3 (TyG index ≥ 2.21) groups according to the tertiles of the TyG index. The differences in SF levels and the prevalence of hyperferritinemia (SF ≥ 300 ng/mL for male or SF ≥ 150 ng/mL for female) were compared. The independent correlations between the TyG index and SF, and between hyperferritinemia and TyG in T2DM patients were analyzed, respectively. RESULTS: SF levels in male T2DM patients were higher in the T3 group (250.12 ng/mL) than in the T1 and T2 groups (180.45 and 196.56 ng/mL, both p < 0.01),while in female patients with T2DM,SF levels were higher in the T3 group (157.25 ng/mL) than in the T1 group (111.06 ng/mL, p < 0.05).The prevalence of hyperferritinemia in male T2DM patients was higher in the T3 group (31.3%) than those in the T1 and T2 groups (10.4% and 17.3%, both p < 0.05).The TyG index was positively correlated with SF levels in T2DM patients (R = 0.178, p < 0.001).TyG index was independently and positively correlated with SF levels after adjusting for confounders (ß = 0.097, 95%CI [2.870,38.148], p = 0.023).The TyG index was positively independently correlated with hyperferritinemia in male T2DM patients (OR = 1.651, 95%CI [1.120,2.432], p = 0.011). CONCLUSIONS: In parallel with increasing TyG index SF levels gradually increased. The TyG index was positively correlated with SF levels in patients with T2DM and was positively correlated with hyperferritinemia in male T2DM patients.


Subject(s)
Diabetes Mellitus, Type 2 , Hyperferritinemia , Humans , Male , Female , Diabetes Mellitus, Type 2/complications , Glucose , Risk Factors , Blood Glucose , Triglycerides
20.
Eur J Gastroenterol Hepatol ; 35(8): 795-802, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37161969

ABSTRACT

It is still debatable whether serum ferritin is a potential prognostic marker in patients with decompensated cirrhosis. In this meta-analysis, we hope to investigate the relationship between elevated serum ferritin and the risk of death in patients with decompensated cirrhosis. We systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, WAN FANG, and ClinicalTrials.gov without language restrictions from inception to 3 October 2022, and finally identified a total of eight eligible studies with 1829 patients. The pooled prevalence of elevated serum ferritin in decompensated cirrhosis was 40.6% [95% confidence interval (CI) 32.1-49.2%], and it was higher in males, patients with alcohol-associated liver disease, those with Child-Pugh grade C, those with hepatic encephalopathy, and nonsurvivors. Nonsurvivors had significantly higher serum ferritin levels than survivors [mean difference 247.90; 95% CI, 130.97-364.84]. With a pooled unadjusted hazard ratio of 2.38 (95% CI, 1.78-3.18), high serum ferritin was associated with an increased risk of death in patients with decompensated cirrhosis, with low heterogeneity among the included studies. In conclusion, high serum ferritin levels were associated with mortality in patients with decompensated cirrhosis. More prospective and homogeneous clinical studies are required to validate our findings.


Subject(s)
Hepatic Encephalopathy , Hyperferritinemia , Liver Diseases, Alcoholic , Humans , Male , Ferritins , Hepatic Encephalopathy/etiology , Hyperferritinemia/complications , Liver Cirrhosis/complications , Liver Diseases, Alcoholic/complications , Prospective Studies
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