铁超载在非酒精性脂肪性肝病中的作用

李光明; 范建高

doi:10.3969/j.issn.1001-5256.2013.12.006

铁超载在非酒精性脂肪性肝病中的作用

DOI: 10.3969/j.issn.1001-5256.2013.12.006

上海交通大学医学院附属新华医院消化内科

基金项目:

国家自然科学基金(81070344&8107322)；中国肝炎基金会王宝恩肝纤维化研究基金(20090007)；上海市科委“创新行动计划”(09140903500)；国家科技部973课题(2012CB517501)；

详细信息

中图分类号: R575.1
计量
- 文章访问数: 3056
- HTML全文浏览量: 15
- PDF下载量: 620
- 被引次数: 0
出版历程
- 收稿日期: 2013-08-19
- 出版日期: 2013-12-20

Research progress in role of iron overload in non- alcoholic fatty liver disease

Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine

Research funding:

摘要

摘要: 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。
- 铁超负荷 /
- 脂肪肝
Abstract: Iron overload is an important research focus in non-alcoholic fatty liver disease ( NAFLD) . The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iron overload and lipid metabolism, and relationship between type of iron deposition and liver damage; the significance of iron overload in the diagnosis and treatment of NAFLD is discussed from iron overload as a new marker of risk stratification and potential therapeutic target in NAFLD. It is currently considered that iron overload, whether the cause or result of NAFLD progression, will promote the progression of NAFLD once it occurs; as a new marker of risk stratification and potential therapeutic target in NAFLD, iron load is worthy of further study.
- iron overload /
- fatty liver

HTML全文

参考文献(31)

[1]VALENTI L, DONGIOVANNI P, FARGION S.Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease[J].World J Gastroenterol, 2012, 18 (29) :3782-3786.

[2]NELSON JE, WILSON L, BRUNT EM, et al.Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease[J].Hepatology, 2011, 53 (2) :448-457.

[3]KOWDLEY KV, BELT P, WILSON LA, et al.Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease[J].Hepatology, 2012, 55 (1) :77-85.

[4]MALIKEN BD, NELSON JE, KLINTWORTH HM, et al.Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease[J].Hepatology, 2013, 57 (5) :1806-1813.

[5]VALENTI L, FRACANZANI AL, BUGIANESI E, et al.HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease[J].Gastroenterology, 2012, 138 (3) :905-912.

[6]MELI R, MATTACE RASO G, LRACE C, et al.High fat diet induces liver steatosis and early dysregulation of iron metabolism in rats[J].PLoS One, 2013, 8 (6) :e66570.

[7]SANTOS PC, KRIEGER JE, PEREIRA AC.Molecular diagnostic and pathogenesis of hereditary hemochromatosis[J].Int J Mol Sci, 2012, 13 (2) :1497-1511.

[8]MOYER TP, HIGHSMITH WE, SMYRK TC, et al.Hereditary hemochromatosis:laboratory evaluation[J].Clin Chim Acta, 2011, 412 (17-18) :1485-1492.

[9]NELSON JE, KLINTWORTH H, KOWDLEY KV.Iron metabolism in Nonalcoholic fatty liver disease[J].Curr Gastroenterol Rep, 2012, 14 (1) :8-18.

[10]O’BRIEN J, POWELL LW.Non-alcoholic fatty liver disease:is iron relevant?[J]Hepatol Int, 2012, 6 (1) :332-341.

[11]HAAP M, MACHANN J, von FRIEDEBURG C, et al.Insulin sensitivity and liver fat:role of iron load[J].J Clin Endocrinol Metab, 2011, 96 (6) :e958-e961.

[12]VALENTI L, DONGIOVANNI P, FRACANZANI AL, et al.Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis[J].Dig Liver Dis, 2003, 35 (3) :172-178.

[13]NELSON JE, BRUNT EM, KOWDLEY KV.Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations[J].Hepatology, 2012, 56 (5) , 1730-1740.

[14]TSUCHIYA H, EBATA Y, SAKABE T, et al.High-fat, high-fructose diet induces hepatic iron overload via a hepcidin-independent mechanism prior to the onset of liver steatosis and insulin resistance in mice[J].Metabolism, 2013, 62 (1) :62-69.

[15]YONEDA M, NOZAKI Y, ENDO H, et al.Serum ferritin is a clinical biomarker in Japanese patients with nonalcoholic steatohepatitis (NASH) independent of HFE gene mutation[J].Dig Dis Sci, 2010, 55 (3) :808-814.

[16]FUJITA N, TAKEI Y.Iron overload in nonalcoholic steatohepatitis[J].Adv Clin Chen, 2011, 55:105-132.

[17]SUMIDA Y, YOSHIKAWA T, OKANOUE T.Role of hepatic iron in non-alcoholic steatohepatitis[J].Hepatol Res, 2009, 39 (3) :213-222.

[18]DONGIOVANNI P, FRACANZANI AL, FARGION S, et al.Iron in fatty liver and in the metabolic syndrome:a promising therapeutic target[J].J Hepatol, 2011, 55 (4) :920-932.

[19]SORRENTINO P, D’ANGELO S, FERBO U, et al.Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis[J].J Heptol, 2009, 50 (2) :351-357.

[20]VALENTI L, SWINKELS DW, BURDICK L, et al.Serum ferritin level are associated with vascular damage in patients with nonalcoholic fatty liver disease[J].Nutr Metab Cardiovasc Dis, 2011, 21 (8) :568-575.

[21]AHMED U, LATHAM PS, OATES PS.Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis[J].World J Gastroenterol, 2012, 18 (34) :4651-4658.

[22]TAN TC, CRAWFORD DH, JASKOWSKI LA, et al.Altered lipid metabolism in HFE-knockout mice promotes severe NAFLD and early fibrosis[J].Am J Physiol Gastrointest Liver Physiol, 2011, 301 (5) :g865-g876.

[23]SUMIDA Y, YONEDA M, HYOGO H, et al.A simple clinical scoring system using ferritin, fasting insulin, and type IV collagen7S for predicting steatohepatitis in nonalcoholic fatty liver disease[J].J Gastroenterol, 2011, 46 (2) :257-268.

[24]MANOUSOU P, KALAMBOKIS G, GRILLO F, et al.Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients[J].Liver Int, 2011, 31 (5) :730-739.

[25]DONGIOVANNI P, VALENTI L, LUDOVICA FRACANZANI A, et al.Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver[J].Am J Pathol, 2008, 172 (3) :738-747.

[26]FACCHINI FS, HUA NW, STOOHS RA.Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease[J].Gastroenterology, 2002, 122 (4) :931-939.

[27]FERNANDEZ-REAL JM, PENARROJA G, CASTRO A, et al.Blood letting in high-ferritin type 2 diabetes:effects on insulin sensitivity and beat-cell function[J].Diabetes, 2002, 51 (4) :1000-1004.

[28]VALENTI L, FRACANZANI AL, DONGIOVANNI P, et al.Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia:evidence from a case-control study[J].Am J Gastroenterol, 2007, 102 (6) :1251-1258.

[29]VALENTI L, MOSCATIELLO S, VANNI E, et al.Venesection for nonalcolholic fatty liver disease unresponsive to lifestyle counselling-a propensity score-adjusted observational study[J].QJM, 2011, 104 (2) :141-149.

[30] VALENTI L, SWINKELS DW, BURDICK L, et al.Serum ferritin level are associated with vascular damage in patients with nonalcoholic fatty liver disease[J].Nutr Metab Cardiovasc Dis, 2011, 21 (8) :568-575.

[31]BEATON MD, CHAKRABARTI S, LEVSTIK M, et al.Phase II clinical trial of phlebotomy for non-alcoholic fatty liver disease[J].Aliment Pharmacol Ther, 2013, 37 (7) :720-729.

施引文献

资源附件(0)

访问统计