Low Serum Transferrin Research Articles

Associations of Dietary Patterns and Vitamin D Levels with Iron Status in Pregnant Women: A Cross-Sectional Study in Taiwan.

Vitamin D is involved in the pathophysiology of anemia. This cross-sectional study was conducted using the Nationwide Nutrition and Health Survey in Pregnant Women in Taiwan database. We investigated associations among dietary patterns (DPs), vitamin D, and iron-related biomarkers in pregnant women. The principal component analysis revealed four DPs. Linear and logistic regression analyses were performed to investigate the association of DPs with anemia-related biomarkers. Plant-based, carnivore, and dairy and nondairy alternatives DPs were positively associated with serum vitamin D levels. After adjusting covariates, the pregnant women consuming plant-based DPs at the mid-tertile (T2) were associated with reduced risks of low serum folate and vitamin D levels, and those consuming carnivore DPs at higher tertiles (T2 and/or T3) were correlated with an increased risk of low serum iron levels but decreased risks of low serum transferrin saturation, vitamin B12, and vitamin D levels. The pregnant women consuming dairy and nondairy alternatives DPs at the highest tertile (T3) were associated with reduced risks of low serum folate and vitamin B12 levels. However, the processed food DP was not correlated with anemia-related biomarkers. Thus, plant-based, carnivore, and dairy and nondairy alternatives DPs were associated with the risk of low-serum-anemia-related variables.

Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1.

Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1. Methods: Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients. Results: Significant changes in mean corpuscular volume and corpuscular hemoglobin were detected in Npc1 -/- mice from an early age. Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron deficiency, increased circulating hepcidin, decreased ferritin and abnormal pro-inflammatory cytokine levels were also found. Furthermore, there is evidence of defective erythrophagocytosis in Npc1 -/- mice and in an in vitro NPC1 cellular model. Comparable hematological changes, including low normal serum iron and transferrin saturation and low cerebrospinal fluidferritin were confirmed in NPC1 patients. Conclusions: These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease.

Juvenile Hemochromatosis With Non-transfused Hemolytic Anemia Caused by a De Novo PIEZO1 Gene Mutation.

Differential diagnosis of juvenile hemochromatosis along with hemolytic anemia is often difficult. We report a 23-year-old woman with macrocytic hemolytic anemia with iron overload. The patient showed high serum ferritin and transferrin saturation and low serum transferrin and ceruloplasmin. We also noticed stomatocytes in her blood smear, which was confirmed by scanning electron microscopy. Target gene sequencing identified a mutation in PIEZO1 (heterozygous c.6008C>A: p.A2003D). This mutation was reported previously in a family with dehydrated hereditary stomatocytosis (DHS1, [OMIM 194380]), but in the current case, it was identified to be a de novo mutation. We underscore DHS1 in the differential diagnosis of iron overload associated with non-transfused hemolytic anemia in children and young adults.

Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1

Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1. Methods: Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients. Results: Significant changes in mean corpuscular volume and corpuscular hemoglobin were detected in Npc1 -/- mice from an early age. Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron deficiency, increased circulating hepcidin, decreased ferritin and abnormal pro-inflammatory cytokine levels were also found. Furthermore, there is evidence of defective erythrophagocytosis in Npc1 -/- mice and in an in vitro NPC1 cellular model. Comparable hematological changes, including low normal serum iron and transferrin saturation and low cerebrospinal fluidferritin were confirmed in NPC1 patients. Conclusions: These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease.

Ferric Carboxymaltose Improves the Quality of Life of Patients with Inflammatory Bowel Disease and Iron Deficiency without Anaemia.

Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (<30 µg/L in the absence of inflammatory activity or <100 µg/L with inflammation) and transferrin saturation index (TSAT) < 16%. The effect on iron levels and HRQoL, according to the health status questionnaires SF-12v2 and EQ-5D, was evaluated 1 month after FCM infusion in an outpatient setting. Results: Of the 105 patients who received FCM, 98 patients completed the study. After 1 month, a single dose of FCM significantly increased serum ferritin, serum iron and TSAT. Importantly, patients reported fewer ID symptoms and problems on all EQ-5D dimensions. They also had higher EQ-5D visual analogue scale and SF-12v2 scores after treatment. FCM had similar clinical effects on men and women and on patients with Crohn’s disease (n = 66) and ulcerative colitis (n = 32). Conclusion: A single dose of FCM rapidly restored iron parameters and significantly improved patients’ symptoms and HRQoL at 1 month after treatment.

Prevalence of iron deficiency anaemia in tuberculosis

Introduction: In India, Tuberculosis is endemic disease with more than 90% of population are in latent infection. In this study we measure the prevalence of iron deficiency anaemia in newly diagnosed TB cases. Methodology: An Observational cross-sectional study was conducted at Respiratory Medicine, MIMS, Nellimarla, Vizianagaram District, and Andhra Pradesh State from July 2020 to June 2021. Inclusion criteria were newly diagnosed TB patients of age &gt;18 years. Exclusion criteria were Immunocompromised, Pregnancy, Patients with malignancy, Patients with past history of TB and who are receiving ATT Unwilling to participate. Results: During the one year study period, a total of 50 patients were included. 32 were male and 18 were female. The study showed decrease in Iron, Hemoglobin, Transferrin and Transferrin saturation and increase in TIBC and Ferritin levels. They are many available methods for assessing anaemia at primary care level and to treat or iron prophylactic supplementation. Conclusion: In the present study, it was concluded that iron metabolism was altered in pulmonary tuberculosis. A low serum iron, transferrin and transferrin saturation with increase in ferritin and TIBC.

SARS-CoV-2 Infects Red Blood Cell Progenitors and Dysregulates Hemoglobin and Iron Metabolism

BackgroundSARS-CoV-2 infection causes acute respiratory distress, which may progress to multiorgan failure and death. Severe COVID-19 disease is accompanied by reduced erythrocyte turnover, low hemoglobin levels along with increased total bilirubin and ferritin serum concentrations. Moreover, expansion of erythroid progenitors in peripheral blood together with hypoxia, anemia, and coagulopathies highly correlates with severity and mortality. We demonstrate that SARS-CoV-2 directly infects erythroid precursor cells, impairs hemoglobin homeostasis and aggravates COVID-19 disease.MethodsErythroid precursor cells derived from peripheral CD34+ blood stem cells of healthy donors were infected in vitro with SARS-CoV-2 alpha variant and differentiated into red blood cells (RBCs). Hemoglobin and iron metabolism in hospitalized COVID-19 patients and controls were analyzed in plasma-depleted whole blood samples. Raman trapping spectroscopy rapidly identified diseased cells.ResultsRBC precursors express ACE2 receptor and CD147 at day 5 of differentiation, which makes them susceptible to SARS-CoV-2 infection. qPCR analysis of differentiated RBCs revealed increased HAMP mRNA expression levels, encoding for hepcidin, which inhibits iron uptake. COVID-19 patients showed impaired hemoglobin biosynthesis, enhanced formation of zinc-protoporphyrine IX, heme-CO2, and CO-hemoglobin as well as degradation of Fe-heme. Moreover, significant iron dysmetablolism with high serum ferritin and low serum iron and transferrin levels occurred, explaining disturbances of oxygen-binding capacity in severely ill COVID-19 patients.ConclusionsOur data identify RBC precursors as a direct target of SARS-CoV-2 and suggest that SARS-CoV-2 induced dysregulation in hemoglobin- and iron-metabolism contributes to the severe systemic course of COVID-19. This opens the door for new diagnostic and therapeutic strategies.Graphical

Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis.

AimsHypophosphataemia is an increasingly recognized side‐effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. The aim of this study was to determine frequency, severity, duration and risk factors of incident hypophosphataemia after treatment with FCM and IIM.MethodsA systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005–2020 was carried out using the search terms ‘ferric carboxymaltose’ OR ‘iron isomaltoside’. Prospective clinical trials reporting outcomes on hypophosphataemia rate, mean nadir serum phosphate and/or change in mean serum phosphate from baseline were selected. Hypophosphataemia rate and severity were compared for studies on IIM vs. FCM after stratification for chronic kidney disease. Meta‐regression analysis was used to investigate risk factors for hypophosphataemia.ResultsAcross the 42 clinical trials included in the meta‐analysis, FCM induced a significantly higher incidence of hypophosphataemia than IIM (47%, 95% CI 36–58% vs. 4%, 95% CI 2–5%), and significantly greater mean decreases in serum phosphate (0.40 vs. 0.06 mmol/L). Hypophosphataemia persisted at the end of the study periods (maximum 3 months) in up to 45% of patients treated with FCM. Meta‐regression analysis identified low baseline serum ferritin and transferrin saturation, and normal kidney function as significant predictors of hypophosphataemia.ConclusionFCM is associated with a high risk of hypophosphataemia, which does not resolve for at least 3 months in a large proportion of affected patients. More severe iron deficiency and normal kidney function are risk factors for hypophosphataemia.

Iron in the General Population and Specificities in Older Adults: Metabolism, Causes and Consequences of Decrease or Overload, and Biological Assessment.

Iron is involved in many types of metabolism, including oxygen transport in hemoglobin. Iron deficiency (ID), ie a decrease in circulating iron, can have severe consequences. We provide an update on iron metabolism and ID, highlighting the particularities in older adults (OAs). There are three iron compartments in the human body: 1) the functional compartment, which consists of heme proteins including hemoglobin, myoglobin and respiratory enzymes; 2) iron reserves (IR), which consist mainly of liver stocks and are stored as ferritin; and 3) transferrin. There are two types of ID. Absolute ID is characterized by a decrease in IR. Its main pathophysiological mechanism is bleeding, which is often digestive and can be due to neoplasia, frequent in OAs. Biological assessment shows low serum ferritin and transferrin saturation (TS) levels. Furthermore, hypochromic microcytic anemia is frequent, and the serum-soluble transferrin receptor (sTfR) level is high. Functional ID, in which IR are high or normal, is due to inflammation, which is also frequent in OAs, particularly in its chronic form. Biological assessments show high serum ferritin, normal or low TS, and normal sTfR levels. Moreover, C-reactive protein is elevated, and there is moderate non-regenerative non-macrocytic anemia. The main characteristics of iron metabolism anomalies in the elderly are the high frequency of ID (20% of ID with anemia in adults ≥85 years) and the severity of its consequences, which include cognitive impairment in case of ID or iron overload and decrease of physical activity in case of ID. In conclusion, causes of ID are frequently intertwined in OAs as a result of the polymorbidity that characterizes them. ID can have dramatic consequences, especially in frail OAs. Thus, measuring the appropriate biological markers prevents errors in the positive diagnosis of ID type, clarifies etiology, and informs treatment-related decision-making.

Low Serum Transferrin Saturation Is Associated with Incident Diabetes in Veterans with CKD

Low Serum Transferrin Saturation Is Associated with Incident Diabetes in Veterans with CKD

Serum levels of ferritin and transferrin serve as prognostic factors for mortality and survival in patients with end‐stage liver disease: A propensity score‐matched cohort study

Patients with end-stage liver disease are known to suffer from a significantly high risk of mortality, but accurate prediction of the course of disease is challenging. The study aim was to evaluate the independent prognostic and clinical importance of serum levels of ferritin and transferrin for 90-day survival of patients with liver disease. Patients with end-stage liver disease treated during a 2-year period were enrolled retrospectively in a single-centre study. Unmatched and propensity score matching (PSM) analyses were applied. The study cohort comprised 286 patients with end-stage liver disease, of which 22.9% died during the observational period. High serum ferritin levels and low serum transferrin levels were associated significantly with increased 90-day mortality in the unmatched (p < 0.001) and PSM study population (p = 0.017). Serum levels of ferritin and transferrin had high prognostic capability to predict 90-day survival similar to the Model for End-stage Liver Disease. Patients with serum ferritin values >1030.5 µg/l had a 50% risk of dying within 11 days after measurement, which translated up to a 90-day mortality of 83%. Serum levels of ferritin and transferrin have independent and excellent capabilities to determine prognosis in patients with end-stage liver disease. Ferritin measurements can reliably identify those with high mortality in daily practice.

Serum transferrin predicts end-stage Renal Disease in Type 2 Diabetes Mellitus patients.

Background: To investigate the relationship between serum iron status and renal outcome in patients with type 2 diabetes mellitus (T2DM).Methods: Chinese patients (n=111) with T2DM and biopsy-proven diabetic nephropathy (DN) were surveyed in a longitudinal, retrospective study. Serum iron, total iron-binding capacity, ferritin, and transferrin were measured at the time of renal biopsy. Iron deposition and transferrin staining were performed with renal biopsy specimens of DN patients and potential kidney donors. End-stage renal disease (ESRD) was the end-point. ESRD was defined as an estimated glomerular filtration rate <15 mL/min/1.73 m2 or the need for chronic renal replacement therapy. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for the influence of serum iron metabolism on ESRD.Results: During a median follow up of 30.9 months, 66 (59.5%) patients progressed to ESRD. After adjusting for age, sex, baseline systolic blood pressure, renal functions, hemoglobin, HbA1c, and pathological findings, lower serum transferrin concentrations were significantly associated with higher ESRD in multivariate models. Compared with patients in the highest transferrin quartile (≥1.65 g/L), patients in the lowest quartile (≤1.15 g/L) had multivariable-adjusted HR (95% confidence interval) of 7.36 (1.40-38.65) for ESRD. Moreover, tubular epithelial cells in DN exhibited a higher deposition of iron and transferrin expression compared with healthy controls.Conclusions: Low serum transferrin concentration was associated with diabetic ESRD in patients with T2DM. Free iron nephrotoxicity and poor nutritional status with accumulated iron or transferrin deposition might contribute to ESRD.

The correlation of intake phytate and tannin on serum transferrin receptor and hemoglobin in stunted overweight adolescents

Stunted overweight teenagers are at risk of having iron deficiency. Iron deficiency is caused by various factors including the high food absorption inhibitors of iron such as phytate and tannins. Phytate and tannin contain polyphenol compounds which have a strong ability to bind iron so that it inhibits iron absorption in the intestine. This study aims to analyze the correlation between phytate, tannin intake and serum transferrin receptor (sTfR) and hemoglobin in stunted overweight adolescents. The research method was a cross-sectional study of 64 stunted overweight adolescents selected by consecutive sampling in four high schools/vocational high schools in Banyumanik District, Semarang City. Phytate and tannin intake data using SQ-FFQ method. The serum transferrin receptor examination uses the ELISA method and the hemoglobin level uses the Cyanomethemoglobin method. The results of the study, most of the respondents had high phytate and tannin intake of 96.9% and 89.1%. Respondents with low serum transferrin receptor were 7.8% and low hemoglobin levels were 7.8%. There was no correlation between phytate intake with serum transferrin receptor or hemoglobin (p1 = 0.937 r1 = -0.010, p2 = 0.192 r2 = 0.165). Tannins were significantly correlated with serum transferrin receptor and hemoglobin (p1 = 0.005 r1 = 0.344, p2 = 0.002 r2 = -0.374). Based on multivariate analysis, tannin is a determinant of hemoglobin (R2 = 0.257). Conclusion is that tannin is positively correlated with serum transferrin receptor and hemoglobin in stunted overweight adolescents. Excessive tannin intake can cause deficiency in stunted overweight adolescents.

The Relevancy of Data Regarding the Metabolism of Iron to Our Understanding of Deregulated Mechanisms in ALS; Hypotheses and Pitfalls

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of motor neurons. Its etiology remains unknown, but several pathophysiological mechanisms are beginning to explain motor neuronal death, as well as oxidative stress. Iron accumulation has been observed in both sporadic and familial forms of ALS, including mouse models. Therefore, the dysregulation of iron metabolism could play a role in the pathological oxidative stress in ALS. Several studies have been undertaken to describe iron-related metabolic markers, in most cases focusing on metabolites in the bloodstream due to few available data in the central nervous system. Reports of accumulation of iron, high serum ferritin, and low serum transferrin levels in ALS patients have encouraged researchers to consider dysregulated iron metabolism as an integral part of ALS pathophysiology. However, it appears complicated to suggest a general mechanism due to the diversity of models and iron markers studied, including the lack of consensus among all of the studies. Regarding clinical study reports, most of them do not take into account confusion biases such as inflammation, renal dysfunction, and nutritional status. Furthermore, the iron regulatory pathways, particularly involving hepcidin, have not been thoroughly explored yet within the pathogenesis of iron overload in ALS. In this sense, it is also essential to explore the relation between iron overload and other ALS-related events, such as neuro-inflammation, protein aggregation, and iron-driven cell death, termed ferroptosis. In this review, we point out limits of the designs of certain studies that may prevent the understanding of the role of iron in ALS and discuss the relevance of the published data regarding the pathogenic impact of iron metabolism deregulation in this disease and the therapeutics targeting this pathway.

Evaluation of Serum Iron and Transferrin in Idiopathic Nephrotic Syndrome Patients Attending Al-Hussein Pediatric Nephrology Clinic

Background: Nephrotic syndrome is characterized by excessive urinary excretion of albumin and other intermediated-size plasma proteins such as transferrin.. Excessive urinary losses of transferrin can produce low serum transferrin level that may lead to low plasma iron concentration and consequently the development of iron resistant microcytic hypochromic anemia. The aim of the work to evaluate changes in serum iron and transferrin and the relationship between the serum and urinary transferrin in the active and remission state of nephrotic syndrome Patients and methods: The present work included fifty children with idiopathic nephrotic syndrome (INS), divided into 2 groups: group A (25 cases in activity) and group B (25 cases in remission). These two groups were age and sex matched with a mean age of (7.74 ± 2.45). All patients in this work were clinically evaluated together with routine laboratory investigations. Serum albumin and urinary alb. /creatinine were assessed. Levels of serum iron, serum ferritin, serum transferrin and urinary transferrin were measured. Results: This work shows that the level of hemoglobin, MCV, HCT were statistically significantly lower in the cases in active state than cases in remission. The mean serum iron, serum ferritin and serum transferrin were significantly lower in the cases in active state than in the cases in remission .The mean urinary transferrin was statistically significantly higher in the cases in active state than in the cases with remission. Conclusion: Urinary transferrin can be considered a reliable parameter for early prediction of iron deficiency anemia in children with active nephrotic syndrome.

Relation between Level of Serum Transferrin and Postoperative Wound Drainage in Closed Long Bone Fractures.

Objective To report association between the serum transferrin level and postoperative wound drainage in closed long bone fractures. Summary of Background Data There is an old association between the serum transferrin level and wound drainage leading to peri-implant infection. There is no literature available on the ideal treatment for wound drainage. In the majority of the cases, wound drainage usually stops in 3–5 days postoperatively. However, very few cases have been described in the literature about wound drainage following closed long bone fractures. Methods A prospective review of the patient's serum transferrin levels and postoperative wound drainage is done. Results We reviewed records of 100 patients in whom levels of serum transferrin were checked preoperatively and correlated with postoperative wound discharge. Out of the 100 patients whose serum transferrin levels were checked, 23 patients had low serum transferrin levels and 19 patients had postoperative wound discharge. Out of these 19 patients, 16 patients had low serum transferrin levels. Thus, sensitivity of the test was 84.2% and specificity was 91.3%. In addition, the positive predictive value was 70% and negative predictive value was 96%. Conclusion We report that preoperative serum transferrin levels can be used as a good marker to judge postoperative wound drainage in closed long bone fractures.

Iron status and anaemia in Sri Lankan secondary school children: A cross-sectional survey

BackgroundIron deficiency, the most common micronutrient disorder and cause of anaemia globally, impairs growth, cognition, behaviour and resistance to infection.Methods/ResultsAs part of a national survey of inherited haemoglobin variants in 7526 students from 72 secondary schools purposefully selected from the 25 districts of Sri Lanka, we studied 5912 students with a normal haemoglobin genotype. Median age was 16.0 (IQR 15.0–17.0) years and 3189 (53.9%) students were males. Most students were Sinhalese (65.7%), with fewer Tamils (23.1%) and Muslims (11.2%). Anaemia occurred in 470 students and was more common in females (11.1%) than males (5.6%). Haemoglobin, serum ferritin, transferrin receptor and iron were determined in 1196 students with low red cell indices and a structured sample of those with normal red cell indices (n = 513). The findings were weighted to estimate the frequencies of iron deficiency and iron deficiency anaemia classified according to WHO criteria. Iron depletion (serum ferritin <15ug/ml) occurred in 19.2% and cellular iron deficiency (low serum ferritin and transferrin receptor >28.1 nmol/l) in 11.6% students. Iron deficiency anaemia (cellular iron deficiency with low haemoglobin) occurred in only 130/2794 (4.6%) females and 28/2789 (1.0%) males. Iron biomarkers were normal in 83/470 (14.6%) students with anaemia. In multiple regression analysis, the odds for iron depletion and cellular iron deficiency were about one-third in males compared with females, and the odds for iron deficiency anaemia were about one fifth in males compared to females. Tamil ethnicity and age <16 years increased the risk of all three stages of iron deficiency and living at high altitude significantly reduced the risk of iron depletion.ConclusionsLow iron status and anaemia remain common problems in Sri Lankan secondary school students especially females, younger students and the socioeconomically disadvantaged Tamil population. More research is needed to identify factors other than low iron status that contribute to anaemia in adolescents.

Childhood Onset Hypoceruloplasminemia Presenting as Early-Onset rebellar Ataxia

The syndrome of hypoceruloplasminemia is a rare autosomal recessive disorder presenting mainly with neurogegeneration, retinal degeneration, and diabetes mellitus. The syndrome, to the best of our knowledge, is not yet recognized in pediatric age group. We screened cases presenting with unexplained cerebellar ataxia and anemia using serum ceruloplasmin, transferrin saturation, and ferritin as biomarkers for hypoceruloplasminemia. An age and sex matched control group was included. Thirty cases (age range 4–17 years) (18 male and 12 female) have been included. The results showed a statistically significant low serum ceruloplasmin and transferrin saturation (18.9±12.1mg/dl and 10.1±5.1%, respectively), and high serum ferritin (124.7±65.7 ng/ml) compared to control group. Four cases have retinal degeneration. The detection of low serum ceruloplasmin concentration and transferrin saturation with high serum ferritin in patients with unexplained cerebellar ataxia is highly suspicious of hypocerluplasminemia which should be subjected for further molecular study.

THU-331 - Low serum transferrin indicates short-term mortality in severe alcoholic hepatitis

THU-331 - Low serum transferrin indicates short-term mortality in severe alcoholic hepatitis

Low serum transferrin correlates with acute‐on‐chronic organ failure and indicates short‐term mortality in decompensated cirrhosis

Iron represents an essential, but potentially harmful micronutrient, whose regulation has been associated with poor outcome in liver disease. Its homeostasis is tightly linked to oxidative stress, bacterial infections and systemic inflammation. To study the prognostic short-term significance of iron parameters in a cohort study of patients with decompensation of cirrhosis at risk of acute-on-chronic liver failure (ACLF). Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were determined in sera from 292 German patients hospitalized for decompensation of cirrhosis with ascites, of which 78 (27%) had ACLF. Short-term mortality was prospectively assessed 30 and 90days after inclusion. Transferrin concentrations were significantly lower, whereas ferritin and TSAT were higher in patients with ACLF compared to patients without ACLF (P≤.006). Transferrin, TSAT and ferritin differentially correlated with the severity of organ failure, active alcoholism and surrogates of systemic inflammation and macrophage activation. As compared with survivors, 30-day non-survivors displayed lower serum transferrin (P=.0003) and higher TSAT (P=.003), whereas 90-day non-survivors presented with higher ferritin (P=.03) and lower transferrin (P=.02). Lower transferrin (continuous or dichotomized at 87mg/dL) and consecutively higher TSAT (continuous or dichotomized >41%) indicated increased mortality within 30days and remained significant after adjustment for organ failure and inflammation in multivariate regression models and across subgroups of patients. Among the investigated indicators of iron metabolism, serum transferrin concentration was the best indicator of organ failure and an independent predictor of short-term mortality at 30days.