By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledg...By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.展开更多
AIM： To investigate whether the patatin-/ike phosph- olipase domain containing-3 gene （PNPLA3） I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis （HH）. ME...AIM： To investigate whether the patatin-/ike phosph- olipase 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 ul- trasound （n = 23）. The PNPLA3 rs738409 single nucle- otide 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 pres- ence 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
We report the case of a 7 years old girl with Juvenile Hemochromatosis, due to homozygous mutation of HJV, which had increased serum iron indices and liver iron overload in the absence of any clinical sign of disease....We report the case of a 7 years old girl with Juvenile Hemochromatosis, due to homozygous mutation of HJV, which had increased serum iron indices and liver iron overload in the absence of any clinical sign of disease. Oral iron chelation with low dose deferasirox showed good efficacy and no side effects. The oral iron chelator deferasirox could be a valid option for removing excess iron in early Juvenile Hemochromatosis.展开更多
AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not e...AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome （MS） was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak＇s score and iron accumulation by Deugnier＇s score; steatosis was diagnosed when present in ≥ 5% of hepatooltes. RESULTS： According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload （P 〈 0.0001）. Patients with ≥2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with 〈 2 MS components and absence of steatosis. CONCLUSION： In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.展开更多
基金Supported by Ministry of University and Research, FIRB 2003 to APAssociation for the Study of Hemochromatosis and Iron Overload Diseases, Monza, to PT and RM+1 种基金Telethon Italy (n° GGP06213)the Cariverona Foundation, Verona, Italy to DG
文摘By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.
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-/ike phosph- olipase 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 ul- trasound （n = 23）. The PNPLA3 rs738409 single nucle- otide 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 pres- ence 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We report the case of a 7 years old girl with Juvenile Hemochromatosis, due to homozygous mutation of HJV, which had increased serum iron indices and liver iron overload in the absence of any clinical sign of disease. Oral iron chelation with low dose deferasirox showed good efficacy and no side effects. The oral iron chelator deferasirox could be a valid option for removing excess iron in early Juvenile Hemochromatosis.
基金Grant from the Association for the Study of Hemochromatosis and Iron Overload Disorders-ONLUS (P.T.), Monza
文摘AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome （MS） was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak＇s score and iron accumulation by Deugnier＇s score; steatosis was diagnosed when present in ≥ 5% of hepatooltes. RESULTS： According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload （P 〈 0.0001）. Patients with ≥2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with 〈 2 MS components and absence of steatosis. CONCLUSION： In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.
