Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Elevated iron stores as indicated by hyperferritinemiawith normal or mildly elevated transferrin saturation a n d m o s t l y m i l d h e p a t i c i r o n d e p o s i t i o n a r e a characteristic finding in subjects with non-alcoholic fatty liver disease(NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the "dysmetabolic iron overload syndrome". Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxylradicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.     

Simultaneous liver iron and fat measures by magnetic resonance imaging in patients with hyperferritinemia

Abstract

Objective. Hyperferritinemia is frequent in chronic liver diseases of any cause, but the extent to which ferritin truly reflects iron stores is variable. In these patients, both liver iron and fat are found in variable amount and association. Liver biopsy is often required to quantify liver fat and iron, but sampling variability and invasiveness limit its use. We aimed to assess single breath-hold multiecho magnetic resonance imaging (MRI) for the simultaneous lipid and iron quantification in patients with hyperferritinemia. Material and methods. We compared MRI results for both iron and fat with their respective gold standards – liver iron concentration and computer-assisted image analysis for steatosis on biopsy. We prospectively studied 67 patients with hyperferritinemia and other 10 consecutive patients were used for validation. We estimated two linear calibration equations for the prediction of iron and fat based on MRI. The agreement between MRI and biopsy was evaluated. Results. MRI showed good performances in both the training and validation samples. MRI information was almost completely in line with that obtained from liver biopsy. Conclusion. Single breath-hold multiecho MRI is an accurate method to obtain a valuable measure of both liver iron and steatosis in patients with hyperferritinemia.     

Estimating Iron Overload in Patients with Suspected Liver Disease and Elevated Serum Ferritin

BackgroundIron status evaluation in patients with suspected liver disease and elevated serum ferritin is often challenging because hyperferritinemia does not always indicate iron overload. A reliable approach to estimate iron overload without exposing the patient to unnecessary investigations would help the clinician to identify patients who may take advantage of iron-removal therapy.MethodsWe analyzed all liver biopsies, including measurement of hepatic iron concentration, performed at the University Hospital Zurich from 1997 to 2010 to identify clinical and laboratory predictors of iron overload in patients with elevated serum ferritin (n = 147).ResultsHyperferritinemia was predictive of iron overload only in patients with a high level of serum ferritin (>2000 μg/L). In patients with moderate hyperferritinemia, liver transaminases inversely correlated with hepatic iron concentration. A combination of both parameters expressed as ferritin/aspartate transaminase ratio was highly predictive of tissue iron overload (sensitivity 83.3%, specificity 78.6%). Receiver operating characteristic analysis resulted in an area under the curve of 0.83.ConclusionsWe established a simple and reliable method to correctly estimate iron overload in patients with suspected liver disease and elevated serum ferritin.     

Dysmetabolic hyperferritinemia is associated with normal transferrin saturation,mild hepatic iron overload,and elevated hepcidin

Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 μmol/g dry weight). Cases had higher serum ferritin than controls (median, 672 μg/L vs. 105 μg/L, p < 0.001), but the median transferrin saturation was not significantly different (38% vs. 36%, p = 0.5). Urinary hepcidin was elevated in dysmetabolic hyperferritinemia (median; 1,584 ng/mg of creatinine vs. 799 ng/mg of creatinine, p = 0.05). Dysmetabolic hyperferritinemia is characterized by hyperferritinemia with normal transferrin saturation, elevated hepcidin levels, and mild liver iron overload in a subset of patients.     

Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease (SCD) who receive chronic or episodic red blood cell transfusions. Iron‐induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging (MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long‐term (over the 5 years prior to enrolment) mean serum ferritin (MSF), spot‐ferritin values and liver iron content (LIC) measured using MRI and liver biopsy. Thirty‐two SCD patients (median age 15 years) with transfusional iron overload were recruited from two U.S. institutions. Long‐term MSF and spot‐ferritin values significantly correlated with LIC by MRI‐R2* (r = 0·77, P < 0·001; r = 0·82, P < 0·001, respectively). LIC by MRI‐R2* had strong positive correlation with LIC by liver biopsy (r = 0·98, P < 0·001) but modest inverse correlation with cardiac MRI‐T2* (r = ?0·41, P = 0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression.     

No evidence for myocardial iron overload and free iron species in multitransfused patients with sickle/β0‐thalassaemia

Iron overload (IO) in the heart is a life‐threatening complication in transfusion‐dependent patients with thalassaemia major (TM) and to a lesser extent in sickle cell disease (SCD), while no data are available in patients with sickle/β⁰‐thalassaemia. Iron deposition in the heart, liver and pancreas was assessed using T2* MRI sequences, as well as free iron species assays – non‐transferrin bound iron (NTBI) and labile plasma iron (LPI), in addition to serum ferritin, percentage transferrin saturation and serum hepcidin, in 10 multitransfused patients (>30 yr) with sickle/β⁰‐thalassaemia. None of the patients had iron deposition in the heart. Three patients had mild, one had moderate, and two had severe liver IO. Two patients had mild iron deposition in the pancreas. In all the patients, serum hepcidin levels were normal – NTBI and LPI were not detected. Possible explanations of these findings are discussed.     

Systematic review and meta‐analysis to determine the impact of iron depletion in dysmetabolic iron overload syndrome and non‐alcoholic fatty liver disease

Aims

Iron reduction has been proposed as treatment for dysmetabolic iron overload syndrome (DIOS) and non‐alcoholic fatty liver disease (NAFLD), but results of published trials are conflicting. We undertook a systematic review and meta‐analysis to determine the impact of phlebotomy in DIOS and NAFLD.

Methods

We searched multiple databases systematically for studies evaluating the impact of phlebotomy in DIOS and NAFLD. We calculated weighted summary estimates using the inverse variance method. Study quality was assessed using the Cochrane collaboration tool.

Results

We identified nine studies with 820 patients (427 had phlebotomy, 393 lifestyle changes alone). Iron depletion did not improve the Homeostasis Model Assessment (HOMA) index (mean difference [MD] ?0.6; confidence interval (CI), ?1.7, 0.5; P = 0.3), insulin level (MD ?0.8 mU/L; CI, ?5.3, 3.7; P = 0.73), or aspartate aminotransferase (AST) (MD ?0.7 IU/L; CI, ?3.2, 1.8; P = 0.6) in DIOS and/or NAFLD patients as compared to lifestyle changes alone (five studies, 626 patients). There was mild improvement in alanine aminotransferase (ALT) (MD ?6.6 IU/L; CI, ?11, ?2.1); P < 0.01), but the effect size was very small (Cohen's d, 0.15; r statistic, 0.07). Even in the subgroup of patients with NAFLD and hyperferritinemia, phlebotomy did not improve the HOMA index, insulin level, ALT, or AST. Additionally, no study showed significant improvement in liver inflammation or fibrosis with iron reduction.

Conclusions

Phlebotomy does not bring about significant improvement in indices of insulin resistance, liver enzymes, or liver histology in patients with DIOS and/or NAFLD compared to lifestyle changes alone. Current evidence does not support the use of phlebotomy in patients with DIOS or NAFLD.

     

Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease

Background and aims

Increased ferritin and body iron stores are frequently observed in nonalcoholic fatty liver disease (NAFLD), associated with heightened susceptibility to vascular damage. Conflicting data have been reported on the role of iron in atherosclerosis, with recent data suggesting that excess iron induces vascular damage by increasing levels of the hormone hepcidin, which would determine iron trapping into macrophages, oxidative stress, and promotion of transformation into foam cells. Aim of this study was to investigate the relationship between iron status and cardiovascular damage in NAFLD.

Methods and results

Vascular damage was evaluated by common carotid arteries intima-media thickness (CC-IMT) measurement and plaque detection by ecocolor-doppler ultrasonography in 506 patients with clinical and ultrasonographic diagnosis of NAFLD, hemochromatosis gene (HFE) mutations by restriction analysis in 342 patients. Serum hepcidin-25 was measured by time-of-flight mass spectrometry in 143 patients. At multivariate analysis CC-IMT was associated with systolic blood pressure, glucose, LDL cholesterol, abdominal circumference, age, and ferritin (p = 0.048). Carotid plaques were independently associated with age, ferritin, glucose, and hypertension. Ferritin reflected iron stores and metabolic syndrome components, but not inflammation or liver damage. Hyperferritinemia was associated with increased vascular damage only in patients with HFE genotypes associated with hepcidin upregulation by iron stores (p < 0.0001), and serum hepcidin-25 was independently associated with carotid plaques (p = 0.05).

Conclusion

Ferritin levels, reflecting iron stores, are independent predictors of vascular damage in NAFLD. The mechanism may involve upregulation of hepcidin by increased iron stores in patients not carrying HFE mutations, and iron compartmentalization into macrophages.     

Assessment of liver and cardiac iron overload using MRI in patients with chronic anemias in Latin American countries: results from ASIMILA study*

ABSTRACT

Objectives: A multicenter, noninterventional, observational study was conducted in the Latin American countries including Argentina, Brazil, Colombia, Mexico, and Venezuela to assess the prevalence of liver and cardiac iron overload using magnetic resonance imaging (MRI) in patients with chronic anemias except thalassemia.

Methods: Patients aged >10 years with transfusion-dependent anemias, except thalassemia, either with <20 units of red blood cell (RBC) transfusions with serum ferritin (SF) levels >2000?ng/mL or with ≥20 units of RBC transfusions regardless of SF level in their lifetime, were enrolled. Iron overload was assessed using MRI.

Results: Among 175 patients included, the majority had sickle cell disease (SCD; 52%), followed by aplastic anemia (AA; 17.7%), myelodysplastic syndrome (MDS; 8.6%), Diamond-Blackfan anemia (DBA; 4%), pure red cell aplasia (1.1%), and others (16.6%). Liver iron overload was observed in 76.4% of patients, while cardiac iron overload was seen in 19.2% when assessed by MRI. The prevalence of iron overload was 80.2% in patients with SCD, 73.3% in MDS, 77.4% in AA, 100% in pure red cell aplasia, 71.4% in DBA, and 68.9% in other transfusion-related disorders. A moderate correlation between liver iron concentration (LIC) and SF was observed in patients with SCD and MDS (r?=?0.47 and r?=?0.61, respectively). All adverse events reported were consistent with the published data for deferasirox or underlying disease.

Conclusion: A high prevalence of iron overload in this patient population in Latin American countries indicates that a better diagnosis and management of iron overload is required in these countries.     

铁超载在非酒精性脂肪性肝病中的作用

铁超载是非酒精性脂肪性肝病（NAFLD）的一个研究热点.从铁超载的评估方法、铁超载与血色病基因突变的关系、铁超载在NAFLD中的发生率及铁超载与NAFLD病情进展的关系等方面归纳了铁超载与NAFLD的相关性;从铁超载的原因、铁超载与脂质代谢的关系及铁沉积类型与肝损伤的关系评述了铁超载参与NAFLD进展的机制;从铁超载作为NAFLD危险分层的新标志物及可能的治疗靶点阐述了铁超载在NAFLD诊疗中的意义.目前认为不论铁超载是NAFLD进展的原因还是结果,一旦出现都将促进NAFLD进展;铁超载作为NAFLD危险分层的新标志物及治疗靶位值得进一步研究.     

Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study

Background

Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).

Methods

We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan^® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively.

Results

After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3–4.0) kPa, 2nd tertile: 5.3 (4.9–5.9) kPa and 3rd tertile: 7.9 (6.7–9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1–147) vs. 85.8 (48.3–139) vs. 111 (59.3–203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1–5.2) vs. 4.4 (2.5–7.3) vs. 4.1 (1.9–6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23–3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15–3.13, p = 0.013).

Conclusions

Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders.     

Hyerferritinemia is a risk factor for steatosis in chronic liver disease

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and g-glutamyltransferase were independent predictors of steatosis. Ferritin levels were significantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION: In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.     

Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging

Objectives: Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy.

Methods: This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy.

Results: The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r?=??0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r?=?0.37) was found between liver iron concentration (LIC) and serum ferritin.

Discussion: The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels.

Conclusion: This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.     

Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis

In the HFE-gene era, precise diagnostic parameters remain important to characterize individual iron stores, because the indication for therapy and prognosis are mainly related to the extent of iron loading. The frequently used serum ferritin interferes with non-iron related factors such as inflammation and may produce falsely positive values. We used a SQUID-biosusceptometer in a large series of patients (n = 679) to measure liver iron concentration in the differential diagnosis and therapy control of hereditary hemochromatosis (SQUID = superconducting quantum interference device). This truly non-invasive technique is sensitive, reliable, fast (online results), and also cost-effective when compared to invasive liver biopsy. Recently, ferritin iron content was propagated as a better parameter than ferritin protein. However, we found a poor correlation between ferritin iron and individual liver iron concentrations in patients with iron overload. Ferritin iron saturation varied in a range between 3 and 10%, independent from liver iron concentration. No differences were found between patients with hemochromatosis and secondary iron overload disease. Only patients with liver cell damage had increased ferritin iron saturations. In conclusion the diagnostic values of serum ferritin protein and iron to assess iron overload are limited.     

Liver Affection in Iron Overload Studied with Serum Ferritin and Serum Aminotransferases

ABSTRACT Liver dysfunction as measured by S-ALAT activity was present in 72% of patients over 40 years of age with HLA-related iron overload, mainly detected by laboratory screening. Liver dysfunction was correlated to the amount of iron stored (r=0.54, p<0.001). When iron was removed by phlebotomy, liver function returned to normal. S-ALAT activity was closely correlated to serum ferritin concentration (r=0.73, p<0.001). Even a mild iron excess can affect hepatocytes and result in increased levels of ferritin and aminotransferases in serum. Patients with “transaminitis” should be investigated for iron overload.     

Hyperferritinemia: causes and significance in a general hospital

ABSTRACT

Objective: To elucidate conditions which cause elevation of the serum ferritin, extent of the elevation in each condition, and clinical relevance of hyperferritinemia in general practice.

Methods: We retrospectively studied medical records of all patients who had at least one serum ferritin measurement above 500?μg?L^?1. Patients who had a marked elevation of the serum ferritin over 10,000?μg?L^?1 were studied separately.

Results: We studied 1394 patients to identify the etiologies of hyperferritinemia. Median serum ferritin level was 1024?μg?L^?1 and 49.2% had ferritin levels of 501–1000?μg?L^?1. The most frequent cause of hyperferritinemia was non-human immunodeficiency virus infection followed by solid tumor, liver dysfunction, renal failure, and hematological malignancy. The distributions of the causes were different among groups stratified by the ferritin level. Forty-one percent had multiple causes and there was a tendency that the more underlying causes a patient had, the higher the ferritin level. Each condition led to a wide range of the ferritin level, and some patients could present with marked hyperferritinemia. Seventy percent of 111 patients with marked hyperferritinemia had multiple etiologies and a variety of diseases could lead to marked hyperferritinemia by themselves.

Discussion: Patients with hyperferritinemia frequently had multiple conditions. The level of the serum ferritin was determined by the underlying conditions to a certain extent; however, the variation was significant. While patients with marked hyperferritinemia mostly had multiple underlying causes, various diseases could cause hyperferritinemia by themselves.

Conclusion: Hyperferritinemia is associated with both etiology and the number of underlying causes.     

Hepcidin response to acute iron intake and chronic iron loading in dysmetabolic iron overload syndrome

Background: The pathogenesis of dysmetabolic iron overload syndrome (DIOS) is still unclear. Hepcidin is the key regulator of iron homeostasis controlling iron absorption and macrophage release. Aim: To investigate hepcidin regulation by iron in DIOS. Methods: We analysed urinary hepcidin at baseline and 24 h after a 65 mg oral iron dose in 24 patients at diagnosis and after iron depletion (n=13) and compared data with those previously observed in 23 healthy controls. Serum iron indices, liver histology and metabolic data were available for all patients. Results: At diagnosis, hepcidin values were significantly higher than in controls (P<0.001). After iron depletion, hepcidin levels decreased to normal values in all patients. At baseline, a significant response of hepcidin to iron challenge was observed only in the subgroup with lower basal hepcidin concentration (P=0.007). In iron‐depleted patients, urinary hepcidin significantly increased after oral iron test (P=0.006). Conclusions: Ours findings suggest that in DIOS, the progression of iron accumulation is counteracted by the increase in hepcidin production and progressive reduction of iron absorption, explaining why these patients develop a mild–moderate iron overload that tends to a plateau.     

Serum Ferritin level,microalbuminuria and non-alcoholic fatty liver disease in type 2 diabetic patients

BackgroundNon-alcoholic fatty liver disease (NAFLD) was considered one of the most common causes of chronic liver disease and is considered the hepatic manifestation of type 2 diabetes mellitus (T2DM). The factors that lead to marked fibrosis and liver cell injury in NAFLD are still remaining undiscovered.Patients and methodsThis study included (40) type 2 diabetic patients with NAFLD and (40) diabetic patients without NAFLD beside 15 healthy persons as a control group. All of them were subjected to full history taking, thorough clinical examination with especial stress on body weight (BW), height, body mass index (BMI), waist-hip ratio, blood pressure. Laboratory tests included serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL), fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG), serum Ferritin and urine microalbuminuria (MAU).ResultsDuration of diabetes, BW, BMI and blood pressure were significantly higher in NAFLD group (P = 0.001). FBG, PBG, TC, TG, LDL, serum Ferritin and MAU were significantly increased in NAFLD group with significant difference between two studied groups as regard HDL. There was a highly significant correlation between serum Ferritin with BW, BMI, duration of diabetes, TC, TG, LDL and MAU. There was a significant correlation between serum Ferritin with age, waist hip ratio, duration of diabetes, SBP, FBG, PBG and HDL. There was a significant correlation between MAU and age, weight, BMI, waist hip ratio, duration of diabetes, DBP, FBG TC, TG, LDL and HDL.ConclusionNAFLD is a common liver disorder in diabetic patients. NAFLD is significantly associated with microalbuminuria and elevated serum Ferritin.     

The association between serum ferritin level,microalbuminuria and non-alcoholic fatty liver disease in non-diabetic,non-hypertensive men

Background: Iron-mediated cell injury may cause glomerular endothelial dysfunction, which precedes microalbumuria. However, there have been no reports on the relationship between serum ferritin level and microalbuminuria. The aim of this study is to assess the relationship between serum ferritin level and microalbuminuria in apparently healthy men and to evaluate how non-alcoholic fatty liver disease (NAFLD) affects this association.

Methods: Microalbuminuria and serum ferritin level were measured, and hepatic ultrasound was performed in a sample of 2489 non-diabetic, non-hypertensive men. The patients were classified into two groups according to urinary albumin–creatinine ratio (UACR) in morning urine specimens: normoalbuminuria (<30?µg/mg) and microalbuminuria (30–300?µg/mg).

Results: The overall prevalence of microalbuminuria and NAFLD based on ultrasound findings were 4.5% (113 subjects) and 41.9% (1042 subjects), respectively. The microalbuminuric group had significantly higher levels of serum ferritin than the normoalbuminuric group (255.4?pmol/L versus 207.5?pmol/L, p?p?p?Conclusions: Our results indicate that serum ferritin level is associated with microalbuminuria in non-hypertensive, non-diabetic men, irrespective of NAFLD.