BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an import...BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.展开更多
BACKGROUND:Increased liver iron stores may contribute to the progression of liver injury and fibrosis,and are associated with a higher risk of hepatocellular carcinoma development.Pre-transplant symptoms of iron overl...BACKGROUND:Increased liver iron stores may contribute to the progression of liver injury and fibrosis,and are associated with a higher risk of hepatocellular carcinoma development.Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients.HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins.This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis.METHODS:Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases.Liver function tests and serum iron markers were assessed in both groups.All patients were screened for HFE mutations (C282Y,H63D,S65C).Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes.RESULTS:The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis.There were no differences in the prevalence of all HFE mutations in both groups.In patients with a diagnosis of hepatocellular carcinoma,no significant associations with iron disorders and HFE gene mutations were found.CONCLUSIONS:Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations.Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis.As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease,there is a need for more extensive studies searching for the possible influence of non-HFE iron homeostasis regulators and their modulation on the course of chronic liver disease and liver cirrhosis.展开更多
Nonspherocytic hereditary anemias are occasionally accompanied by significant iron overload but the significance for the development of chronic liver disease is not clear. We described two cases of patients with chron...Nonspherocytic hereditary anemias are occasionally accompanied by significant iron overload but the significance for the development of chronic liver disease is not clear. We described two cases of patients with chronic liver d isease and severeiron overload due to chronic hereditary hemolysis. Both patients have had signs of liver cirrhosis and severe hemolysis since childhood. A hereditary pyruvate kinase deficiency (PKD) was discovered as the underlying reason for the hemolysis.Sequencing of the pyruvate kinase gene showed a mutation within exon 11. Liver histology in both patients revealed cirrhosis and a severe iron overload but primary hemochromatosis was excluded by HFE-gene analysis.An iron reduction therapy with desferrioxamine led to significant decrease of serum ferritin and sustained clinical improvement. PKD-induced hemolysis may cause severe iron overload even in the absence of HFE-genotype abnormalities. This secondary iron overload can lead to chronic liver disease and cirrhosis. Therefore, the iron metabolism of PKD patients has to be closely monitored and iron overload should be consequently treated.展开更多
BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver ...BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non- alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serummarkers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.展开更多
Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients...Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer.展开更多
Purpose: To improve liver iron load assessment by investigating the precision of different approaches of T2* Measurement. Background: Iron overload is a major problem in the treatment of thalassemic patients. Liver ir...Purpose: To improve liver iron load assessment by investigating the precision of different approaches of T2* Measurement. Background: Iron overload is a major problem in the treatment of thalassemic patients. Liver iron concentration (LIC) is an important index toward the management of body iron load. The accuracy of iron load estimation may suffer from the methodology of T2* measurement and there is no complete agreement upon the best approach of T2* calculation. Methods: 32 β-thallasemic patients (18 male) with the mean age of 20.0 ± 6.5 years were involved in this study. A multi-echo fast gradient-echo technique on a 1.5 T MRI system was used to measure liver iron overload and the T2* map of liver was reconstructed on a pixel-by-pixel basis. The T2* map and MRI images were utilized to deter- mine accurate location of ROI (region of interest). The mean of T2* were computed from the ROIs. The reproducibility of calculated T2* values in two methods were obtained. Moreover, the mean of the pixel’s T2* was calculated in the entire liver parenchyma of one slice. The T2* value of the entire slice was compared with the ROI approach. Results: In the ROI based method, the CoV for the intra-observer reproducibility was 8.5% and for the inter-observer was 9.78%. In the pixel based method, the CoVs for intra-observer and inter-observer reproducibility were 2.79% and 3.91%. There was an acceptable correlation (r = 0.96) between the T2* values calculated by the ROI and the entire slice. Conclusions: The pixel-based approach is more precise to determine the appropriate placement of the ROI. The assessment of T2* in the entire slice reduces the user-based errors significantly.展开更多
AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with be...AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with beta-thalassemia major having regular blood transfusions were consecutively enrolled. Serum ferritin levels were measured, and all patients underwent MRI T2* of the liver. Liver biopsy was performed in 53 patients at an interval of no longer than 3 mo after the MRIT2* in each patient. The amount of iron was assessed in both MRI T2* and liver biopsy specimens of each patient. RESULTS: Patients’ ages ranged from 8 to 54 years with a mean of 24.59 ± 8.5 years. Mean serum ferritin level was 1906 ± 1644 ng/mL. Liver biopsy showed a moderate negative correlation with liver MRI T2* (r = -0.573, P = 0.000) and a low positive correlation with ferritin level (r = 0.350, P = 0.001). Serum ferritin levels showed a moderate negative correlation with liver MRI T2* values (r = -0.586, P = 0.000). CONCLUSION: Our study suggests that MRI T2* is a non-invasive, safe and reliable method for detecting iron load in patients with iron overload.展开更多
The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitocho...The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.展开更多
Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and e...Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.展开更多
AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3 ) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS:...AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3 ) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine amino-transaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION: The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH.展开更多
Advances in recent years in the understanding of, and the genetic diagnosis of hereditary hemochromatosis (HH) have changed the approach to iron overload he-reditary diseases. The ability to use a radiologic tool (MRI...Advances in recent years in the understanding of, and the genetic diagnosis of hereditary hemochromatosis (HH) have changed the approach to iron overload he-reditary diseases. The ability to use a radiologic tool (MRI) that accurately provides liver iron concentration determination, and the presence of non-invasive sero-logic markers for fibrosis prediction (ser um ferritin, platelet count, transaminases, etc), have diminished the need for liver biopsy for diagnosis and prognosis of this disease. Consequently, the role of liv er biopsy in iron metabolism disorders is changing. Furthermore, the irruption of transient elastography to assess liver stiffness, and, more recently, the ability to determine liver f ibrosis by means of MRI elastography will change this role even more, with a potential drastic decline in hepatic biopsies in years to come. This review will provide a brief summary of the different non-invasive methods available nowadays for diagnosis and prognosis in HH, and point out potential new techniques that could come about in the next years for fibrosis prediction, thus avoiding the need for liver biopsy in a greater number of patients. It is possible that liver biopsy will remain useful for the diagnosis of associated diseases, where other non-invasive means are not po-ssible, or for those rare cases displaying discrepancies between radiological and biochemical markers.展开更多
基金supported by a grant from Polish National Science Centre(2011/01/B/NZ6/00320)
文摘BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.
基金supported by a grant from the Medical University of Gdansk (W-175)
文摘BACKGROUND:Increased liver iron stores may contribute to the progression of liver injury and fibrosis,and are associated with a higher risk of hepatocellular carcinoma development.Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients.HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins.This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis.METHODS:Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases.Liver function tests and serum iron markers were assessed in both groups.All patients were screened for HFE mutations (C282Y,H63D,S65C).Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes.RESULTS:The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis.There were no differences in the prevalence of all HFE mutations in both groups.In patients with a diagnosis of hepatocellular carcinoma,no significant associations with iron disorders and HFE gene mutations were found.CONCLUSIONS:Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations.Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis.As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease,there is a need for more extensive studies searching for the possible influence of non-HFE iron homeostasis regulators and their modulation on the course of chronic liver disease and liver cirrhosis.
文摘Nonspherocytic hereditary anemias are occasionally accompanied by significant iron overload but the significance for the development of chronic liver disease is not clear. We described two cases of patients with chronic liver d isease and severeiron overload due to chronic hereditary hemolysis. Both patients have had signs of liver cirrhosis and severe hemolysis since childhood. A hereditary pyruvate kinase deficiency (PKD) was discovered as the underlying reason for the hemolysis.Sequencing of the pyruvate kinase gene showed a mutation within exon 11. Liver histology in both patients revealed cirrhosis and a severe iron overload but primary hemochromatosis was excluded by HFE-gene analysis.An iron reduction therapy with desferrioxamine led to significant decrease of serum ferritin and sustained clinical improvement. PKD-induced hemolysis may cause severe iron overload even in the absence of HFE-genotype abnormalities. This secondary iron overload can lead to chronic liver disease and cirrhosis. Therefore, the iron metabolism of PKD patients has to be closely monitored and iron overload should be consequently treated.
基金supported by agrant from Medical University of Gdansk(W-175)
文摘BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non- alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serummarkers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.
文摘Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer.
文摘Purpose: To improve liver iron load assessment by investigating the precision of different approaches of T2* Measurement. Background: Iron overload is a major problem in the treatment of thalassemic patients. Liver iron concentration (LIC) is an important index toward the management of body iron load. The accuracy of iron load estimation may suffer from the methodology of T2* measurement and there is no complete agreement upon the best approach of T2* calculation. Methods: 32 β-thallasemic patients (18 male) with the mean age of 20.0 ± 6.5 years were involved in this study. A multi-echo fast gradient-echo technique on a 1.5 T MRI system was used to measure liver iron overload and the T2* map of liver was reconstructed on a pixel-by-pixel basis. The T2* map and MRI images were utilized to deter- mine accurate location of ROI (region of interest). The mean of T2* were computed from the ROIs. The reproducibility of calculated T2* values in two methods were obtained. Moreover, the mean of the pixel’s T2* was calculated in the entire liver parenchyma of one slice. The T2* value of the entire slice was compared with the ROI approach. Results: In the ROI based method, the CoV for the intra-observer reproducibility was 8.5% and for the inter-observer was 9.78%. In the pixel based method, the CoVs for intra-observer and inter-observer reproducibility were 2.79% and 3.91%. There was an acceptable correlation (r = 0.96) between the T2* values calculated by the ROI and the entire slice. Conclusions: The pixel-based approach is more precise to determine the appropriate placement of the ROI. The assessment of T2* in the entire slice reduces the user-based errors significantly.
基金Supported by The Gastrointestinal and Liver Disease Research Center of Tehran University of Medical Sciences
文摘AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with beta-thalassemia major having regular blood transfusions were consecutively enrolled. Serum ferritin levels were measured, and all patients underwent MRI T2* of the liver. Liver biopsy was performed in 53 patients at an interval of no longer than 3 mo after the MRIT2* in each patient. The amount of iron was assessed in both MRI T2* and liver biopsy specimens of each patient. RESULTS: Patients’ ages ranged from 8 to 54 years with a mean of 24.59 ± 8.5 years. Mean serum ferritin level was 1906 ± 1644 ng/mL. Liver biopsy showed a moderate negative correlation with liver MRI T2* (r = -0.573, P = 0.000) and a low positive correlation with ferritin level (r = 0.350, P = 0.001). Serum ferritin levels showed a moderate negative correlation with liver MRI T2* values (r = -0.586, P = 0.000). CONCLUSION: Our study suggests that MRI T2* is a non-invasive, safe and reliable method for detecting iron load in patients with iron overload.
文摘The underlying pathophysiology of liver dysfunction in urea cycle disorders(UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle(UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liverdamage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.
基金Supported by First Università degli Studi di Milano 2007,2008,to Valenti L and Fargion SRicerca corrente Ospedale Maggiore Policlinico 2006 and 2008,to Valenti L and FargionSCentro per lo Studio delle Malattie del Fegato e del Metabolismo
文摘Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.
基金Supported by FIRST Università degli Studi di Milano 2007,2008 to Valenti L, Fargion SRicerca corrente Ospedale Maggiore Policlinico 2006 and 2008 to Valenti L, Fargion SCentro per lo Studio delle Malattie del Fegato e del Metabolismo
文摘AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3 ) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine amino-transaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION: The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH.
文摘Advances in recent years in the understanding of, and the genetic diagnosis of hereditary hemochromatosis (HH) have changed the approach to iron overload he-reditary diseases. The ability to use a radiologic tool (MRI) that accurately provides liver iron concentration determination, and the presence of non-invasive sero-logic markers for fibrosis prediction (ser um ferritin, platelet count, transaminases, etc), have diminished the need for liver biopsy for diagnosis and prognosis of this disease. Consequently, the role of liv er biopsy in iron metabolism disorders is changing. Furthermore, the irruption of transient elastography to assess liver stiffness, and, more recently, the ability to determine liver f ibrosis by means of MRI elastography will change this role even more, with a potential drastic decline in hepatic biopsies in years to come. This review will provide a brief summary of the different non-invasive methods available nowadays for diagnosis and prognosis in HH, and point out potential new techniques that could come about in the next years for fibrosis prediction, thus avoiding the need for liver biopsy in a greater number of patients. It is possible that liver biopsy will remain useful for the diagnosis of associated diseases, where other non-invasive means are not po-ssible, or for those rare cases displaying discrepancies between radiological and biochemical markers.
